The fate of incompetent perforating veins after surgery for primary

varicose veins

by

Babak Kianifard FRCS

Submitted for the degree of Doctorate of Medicine Postgraduate Medical School

University of Surrey

JULY 2005© Babak Kianifard 2005

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ABSTRACT

Background: Studies have suggested that Incompetent Perforator Veins (IPV)

become competent following High Saphenous Tie and Stripping (HST&S) of the

Great Saphenous Vein (GSV). Other studies show an association between IPV and

both primary and recurrent varicose veins. The role of Incompetent perforator veins

(IPV) in primary non-ulcerated varicose veins has not been established. The aim of

this randomised trial was to assess the fate of IPV after HST&S with or without

Subfascial Endoscopic Perforator Surgery (SEPS). Also as secondary outcome

measures photoplethysmography, quality of life and visual analogue scores were

assessed over a 12 month period following surgery.

Materials and Methods:

Local ethical committee approval was obtained. Inclusion criteria consisted of

patients with duplex proven GSV reflux and IPV (reflux > 0.5 s). Those with deep

venous reflux, sapheno-popliteal vein reflux, ulceration and recurrent varicose veins

were excluded. Patients were randomly allocated to HST&S alone (NSEPSG) or

HST&S plus SEPS (SEPSG). Standardised operations were performed by one of two

consultant vascular surgeons. Each patient completed a post-operative diary for 2

weeks (VAS for pain, and mobility, number of pain-killers taken and the amount of

daily assistance required). Follow-up assessments were made at I week, 6 weeks, 6

months and I year. As part of the assessment each subject had repeat Duplex

Ultrasound (DU) performed by a single senior vascular technologist. They also filled

QOL questionnaires (SF-36 and Aberdeen Questionnaires), underwent

Photoplethysmography (PPG), were timed walking a fixed distance, and completed

VAS sheets for pain mobility and cosmesis (all also performed pre-operatively).

Other data such as risk factors, CEAP classification, body mass index (BMI), family

history and number of hours standing were also assessed. The end point of the study

was 1 year from the operation.

Results: Seventy two patients were recruited (powered to 0.95). Thirty-two were

randomised to the NSEPSG (M:F 13:19, mean age 53.4), 38 to SEPSG (M:F=23:15,

mean age 53.4). Two patients were excluded, one withdrew and the other was

excluded due to undergoing the wrong treatment.

The patients in the two groups were similar with respect to the grade of their varicose

veins and risk factors. The SEPSG had a significant increase in operative time of 16

minutes which was due to the SEPS procedure. There were no differences in the post­

operative diaries filled by the patients. During the follow-up period there were no

differences in the two groups with respect to the VAS, QOL assessments, or PPG

times. In the NSEPSG there was a significant increase in the number of patients with

IPV as assessed by DU at one year (25/32 vs. 12/38 in the SEPSG, P<0.001). Also the

majority of these perforators were the same ones seen on the pre-operative DU (37/46

(80%) vs. 5/19 (26%) in SEPSG).

Conclusions: IPV do not remain closed following HST and stripping. The addition of

SEPS to HST&S increases operative time by an average of 16 minutes and is not

associated with increases pain, immobility or cosmetic deterioration. SEPS is

effective in treating IPV.

CONTENTS

ABSTRACT.......................................................................................................................................... 2

CONTENTS......................................................................................................................................... 4

CONSORT STATEMENT................................................................................................................ 7

LIST OF FIGURES............................................................................................................................ 8

LIST OF TABLES.............................................................................................................................10

ACKNOWLEDGEMENTS................................................................. 12

ABBREVIATION..............................................................................................................................14

1 CHAPTER 1 ..............................................................................................................................15

1.1 INTRODUCTION..............................................................................................................151.2 ANATOMY....................................................................................................................... 19

1.2.1 Superficial Venous System of the Lower Limb....................................................201.2.2 The Greater Saphenous Vein (GSV)...................................................................211.2.3 Small saphenous vein (SSV)............................................................................... 221.2.4 Deep Venous System of the Lower Limb............................................................ 231.2.5 Perforating Veins............................................................................................... 25

1.3 PHYSIOLOGY..................................................................................................................271.3.1 The Venous Wall................................................................................................ 281.3.2 Valves..................................................................................................................291.3.3 Venous Pump......................................................................................................29

1.3.3.1 The Foot, Calf, Thigh, Abdominal and Thoracic Pumps.............................. 301.3.4 Failure of Pump................................................................................................. 32

1.4 AETIOLOGY.....................................................................................................................331.4.1 Congenital Venous Insufficiency.........................................................................331.4.2 Primary Venous Insufficiency............................................................................ 331.4.3 Secondary Venous Insufficiency......................................................................... 351.4.4 CEAP Classification.......................................................................................... 36

1.5 PATHOGENESIS............................................................................................................. 381.5.1 Primary Varicose veins...................................................................................... 381.5.2 Descending Theory............................................................................................ 401.5.3 Ascending Theory...............................................................................................411.5.4 Fascio-cutaneous Changes................................................................................ 44

1.6 EPIDEMIOLOGY............................................................................................................. 451.6.1 Varicose Veins.....................................................................................................451.6.2 Fascio-cutaneous Changes................................................................................ 471.6.3 Primary and Chronic Venous Insufficiency....................................................... 47

1.7 INVESTIGATIONS OF VEINS..................................................................................... 481.7.1 Investigation of Venous Anatomy....................................................................... 48

1.7.1.1 Phlebography........................................................................................................491.7.1.1.1 Ascending Phlebography.............................................................................491.7.1.1.2 Varicography..................................................................................................501.7.1.1.3 Saphenography...............................................................................................501.7.1.1.4 Descending Phlebography............................................................................ 511.7.1.1.5 Complications o f Phlebography.................................................................. 51

1.7.1.2 Ultrasound (U S).................................................................................................. 521.7.1.2.1 Real Time Ultrasound (two dimensional echo)........................................541.7.1.2.2 Duplex Ultrasound........................................................................................ 541.7.1.2.3 Choice o f Frequency.....................................................................................55

1.7.1.3 Investigation o f Choice...................................................................................... 561.7.1.4 Assessment o f Incompetent Perforator Veins.................................................59

1.7.2 Investigation of Venous Function.......................................................................621.7.2.1 Tourniquet Test (Trendelenburg Test).............................................................621.7.2.2 Continuous Wave Doppler Ultrasound............................................................63

1.7.2.2.1 Gated or Pulsed Doppler.............................................................................. 631.7.2.3 Foot Volumetry................................................................................................... 641.7.2.4 Ambulatory Venous Pressure Measurements (AVP).....................................641.7.2.5 Plethysmography................................................................................................. 65

1.7.2.5.1 Strain-gauge Plethysmography...................................................................661.7.2.5.2 Air Plethysmography....................................................................................661.7.2.5.3 Impedance Plethysmography...................................................................... 661.7.2.5.4 Photoplethysmography (PPG).................................................................... 67

1.8 VARICOSE VEIN SURGERY....................................................................................... 701.8.1 Great Saphenous Vein Surgery..........................................................................701.8.2 Perforator Vein Surgery and Subfascial Endoscopic Perforator Surgery (SEPS)

721.8.3 Perforator Vein Surgery in Primary Non Ulcerated Varicose Veins................... 76

1.9 RECURRENT VARICOSE VEINS............................................................................... 811.9.1 Inadequate or Inappropriate Surgery..................................................................81

1.9.1.1 Failure o f Sapheno-Femoral Ligation Or Missed Branches at the Junction 81

1.9.1.2 Aberrant Anatomy...............................................................................................831.9.1.3 Incompetent Thigh or Calf Perforators.............................................................84

1.9.2 Regeneration / Neo-vascularization.................................................................... 851.9.3 Denovo Reflux................................................................................................... 87

1.10 Quality of Life Assessment....................................................................................... 881.10.1 Short Form 36 (SF36)................................................................................... 901.10.2 Aberdeen Questionnaire................................................................................94

CHAPTER 2 ........................................................................................................... 972.1 METHODS AND MATERIALS................................................................................... 97

2.1.1 Proposal and Ethical Approval..........................................................................972.1.2 Sample Size......................................................................................................... 982.1.3 Patient Groups....................................................................................................982.1.4 Operative Intervention.......................................................................................101

2.1.4.1 High Tie and Strip.............................................................................................1012.1.4.2 SEPS....................................................................................................................1022.1.4.3 Avulsions:...........................................................................................................104

2.1.5 Outcome.......................................................................................................... 1052.1.6 Assessment........................................................................................................105

2.1.6.1 Visual Analogue Score (V A S)........................................................................1062.1.6.2 Gait......................................................................................................................1072.1.6.3 QOL.....................................................................................................................1072.1.6.4 Duplex Ultrasound............................................................................................1082.1.6.5 Photoplethysmography (PPG).........................................................................1092.1.6.6 Data Collection.................................................................................................. 1102.1.6.7 Statistical Analysis............................................................................................1102.1.6.8 Summary o f Outcome Measures.....................................................................112

CHAPTERS......................................................................................................... 1153.1 RESULTS........................................................................................................................ 115

3.1.1 Patients............................................................................................................1163.1.2 Data Collection.................................................................................................1173.1.3 CEAP Classification......................................................................................... 1183.1.4 Duration of Varicose Veins............................................................................... 1193.1.5 Family History..................................................................................................120

5.1.6 Standing ........................................................................................................................... 1213.1.7 Surgery..............................................................................................................................1223.1.8 Patient D iary ................................................................................................................... 125

3.1.8.1 VAS for Pain..........................................................................................................1263.1.8.2 VAS for M obility..................................................................................................1283.1.8.3 Pain R elief.............................................................................................................. 1283.1.8.4 Assistance................................................................................................................129

3.1.9 Follow-up Assessment................................................................................................... 1313.1.9.1 Days O ff..................................................................................................................1313.1.9.2 Visual Analogue Scores (V A S)..........................................................................132

3.1.9.2.1 P ain .................................................................................................................... 1323.1.9.2.2 Mobility..............................................................................................................1353.1.9.2.3 Cosmetic Appearance.................................................................................... 137

3.1.9.3 Walking Assessm ent............................................................................................1383.1.9.4 Quality o f L ife....................................................................................................... 1393.1.9.5 SF-36........................................................................................... 1393.1.9.6 Aberdeen Questionnaire...................................................................................... 1463.1.9.7 Photoplethysmography (PPG)............................................................................1483.1.9.8 Duplex Ultrasound............................................................................................... 152

3.1.9.8.1 Subfascial Endoscopic Perforator Surgery Group (SEPS)..................... 1523.1.9.8.2 Non Subfascial Endoscopic Perforator Surgery Group (NSEPSG).... 153

4 CHAPTER 4 ............................................................................................................................159

4.1 Venous Pressure Monitoring ................................................................................... 1594.1.1 Methods and M aterials .................................................................................................1604.1.2 Results...............................................................................................................................162

5 CHAPTERS.................... 164

5.1 D iscu ssio n .......................................................................................................................... 164

FUTURE WORK AND QUESTIONS....................................................................................... 170

APPENDIX 1.................................................................................................................................... 173

Patient information sh eet ........................................................................................................173Consent f o r m .................................................................................................................................. 175Pre-operative pro-fo rm a ........................................................................................................... 176POST-OPERATIVE D IA R Y .......................................................................................................... 181

APPENDIX 2 .................................................................................................................................... 182

Study A ppraisal Questionnaire..............................................................................................182A ssessing Cohort stu d ies .......................................................................................................... 183A ssessing Case Control Studies ............................................................................................ 184A ssessing Clinical Trials.......................................................................................................... 185

REFERENCES................................................................................................................................186

PAPERS, ABSTRACTS AND PRESENTATIONS................................................................205

SYSTEMATIC REVIEW ............................................................................................................. 206

CONSORT STATEMENT (Moher D et al 2001)

PAPER SECTION Item Reportei

No. on page No.

TITLE & ABSTRACT 1 1 -2

INTRODUCTIONBackground 2 14-93METHODSParticipants 3 97-99Interventions 4 100-103Objectives 5 96Outcomes 6 96Sample size 7 97Randomization:Sequence generation 8 99Allocation concealment 9 99Implementation 10 106Blinding (Masking) 11 99Statistical methods 12 109RESULTSParticipant flow 13 114Recruitment 14 115Baseline data 15 116Numbers analyzed 16 117Outcomes and Estimation 17 151 -152Ancillary analyses 18Adverse events 19DISCUSSIONInterpretation 20 158-164Generalizability 21 158-166Overall evidence 22 158-166

LIST OF FIGURES

Figure 1 Figure showing the superficial venous anatomy (reproduced courtesy of Mr B

Price)...........................................................................................................................................19

Figure 2 Figure depicting venous anatomy (reproduced by permission of Mr B Price). 22

Figure 3 Deep venous anatomy (reproduced by permission of Mr B Price)...................... 24

Figure 4 DU being performed on a patient in the trial.............................................................56

Figure 5 Colour DU showing flow within a perforator vein crossing the fascia................61

Figure 6 PPG probe in position on the medial aspect of the lower calf..............................68

Figure 7 Figure showing the observed changes with simultaneous PPG and ambulatory

venous pressure (AVP) monitoring (After Norris et a/.1983)........................................69

Figure 8 IPV as first seen during the operation.........................................................................75

Figure 9 IPV dissected ou t.............................................................................................................. 75

Figure 10 SEPS clips across an IPV which is divided in this case......................................... 75

Figure 11 SEPS procedure............................................................................................................ 103

Figure 12 SEPS procedure........................................................................................................... 103

Figure 13 Chart depicting the distribution of clinical classification (CEAP) in SEPSG

and NSEPSG............................................................................................................................1 1 9

Figure 14 Bar chart showing the distribution of number of years with varicose veins. 120

Figure 15 Distribution of positive family history in the two groups of patients 121

Figure 16 Estimated number of hours standing during the day by each patient in the 2

groups........................................................................................................................................122

Figure 17 Graphical representation of mean daily VAS for pain during 14 post­

operative days as recorded in the patient diary..............................................................127

Figure 18 Mean VAS for mobility as recorded in the patient diary....................................128

Figure 19 Mean number of daily analgesic tablets taken by each patient as recorded in

the patient diary......................................................................................................................129

Figure 20 Assistance required as patient diary........................................................................ 130

Figure 21 Graph demonstrating the number of days taken off work/normal activity in

each group........................ 132

Figure 22 Mean VAS for pain at follow up visits....................................................................134

Figure 23 Mean VAS for mobility at follow-up visits..............................................................136

Figure 24 Mean visual analogue score for cosmetic appearance of legs during the follow-

up period...................................................................................................................................138

Figure 25 Graph representing mean walking times over marked out distance of 30m in

the two groups......................................................................................................................... 139

Figure 26 Figure showing the mean scores of the SF-36 dimensions pre-operatively and

at one year for the SEPSG and NSEPSG as well as the mean values representing

the general population...........................................................................................................1 4 5

Figure 27 Figure showing the mean scores of the SF-36 dimensions pre-operatively and

at one year for the SEPSG and NSEPSG as well as the mean values representing

the general population...........................................................................................................1 4 5

Figure 28 Figure representing the Aberdeen score for the two groups during the follow-

up period....................................................................................................................................

Figure 29 Graphical representation of PPG derived T90 times in secs, for SEPSG (pre­

op. and at one year)................................................................................................................150

Figure 30 Graphical representation of PPG derived T90 times in seconds in NSEPSG

(pre-op. and at one year).......................................................................................................1 5 0

Figure 31 Graphical representation of changes in pressure observed in the foot veins. 163

Figure 32 Graphical representation of the difference in the observed pressures........... 163

Figure 33 Graph showing the no. of same IPV in the 2 groups........................................... 165

Figure 34 No. of New IPV seen during the follow-up period................................................ 165

Figure 35 Seldinger technique used in the introduction of the TRLOP catheter........... 172

Figure 36 RFS catheter...................................................................................................................172

LIST OF TABLES

Table 1 Consort table showing flow of participants................................................................115

Table 2 Demographics of the two groups (SEPSG - Subfascial Endoscopic Perforator

Surgery Group, NSEPSG — Non Subfascial Endoscopic Perforator Surgery Group,

SD one standard deviation, t-test performed for the P values indicated below, non

were significant)..................................................................................................................... 1 1 7

Table 3 Response rate and completion rate of data collection..............................................118

Table 4 Summarising the operative data gathered. * statistically significant, M=missing

data)...........................................................................................................................................123

Table 5 Summarising the hospital stay for the SEPS and NSEPS groups..................... 125

Table 6 Showing the patient diary responses at day 1 and day 14...................................126

Table 7 Mean visual analogue scores for pain in the SEPSG and NSEPSG during the

follow-up period, *Mann-Whitney U................................................................................ 133

Table 8 Variance analysis for VAS for pain............................................................................. 134

Table 9 Mean visual analogue scores for mobility during follow-up in the SEPSG and

NSEPSG, * Mann-Whitney U............................................................................................1 3 5

Table 10 Variance analusis for VAS for mobility..................................................................136

Table 11 Mean visual analogue scores for cosmetic appearance during the follow-up

period in the SEPSG and NSEPSG, * Mann-Whitney U ...........................................137

Table 12 Variance analysis for VAS cosmesis.........................................................................137

Table 13 Summary of the mean SF36 scores out of 100, in the two groups during the

follow-up period, (M= Missing Data, * General population data as per Baker et al.

1995, Brazier et al. 1992, $ Significant difference from the general population, all

other data no significant difference seen between the 2 groups, Mann Whitney U

test P>0.05)..............................................................................................................................1 41

Table 14 Representing the variance analysis carried out with respect to SF36 scors,*

statistical significance.......................................................................................................... 142

Table 15 Mean Aberdeen questionnaire score for the two group, *Mann whitney U,

**significant............................................................................................................................1 4 6

Table 16 Analysis of variance for Aberdeen questionnaire,* statistical significance.... 147

Table 17 showing the mean RT90 times in the 2 groups during the study, *Mann-

Whitney U, ** significant....................................................................................................1 4 9

Table 18 Analysis of variance for PPG results........................................................................ 149

Table 19 Summarising findings in patients with shorter RT 90 at one year compared to

pre-operative times. (M=missing, * with in normal limits, **accessory GSV).......151

10

Table 20 summarising the ultrasound findings in SEPSG with respect to IPV. (n = new

IPV not seen on the pre-op. DU, s = same perforators as seen on the pre-op. DU).

.....................................................................................................................................................153

Table 21 Summarising the ultrasound findings in NSEPS Group with respect to IPV.

(n=new IPV i.e. not seen on the pre-op. DU, s = same perforators as seen on the

pre-op. DU).............................................................................................................................. 156

Table 22 Summary of IPV found on DU in the 2 groups during the follow-up period. *

Significant difference between the two groups (Chi square test, P<0.001)..............157

Table 23 MEDLINE (population and intervention) search criteria................................... 212

Table 24 EMBASE (Duplex ultrasound) search criteria.......................................................213

11

ACKNOWLEDGEMENTS

I would like to thank a large number of people without whose help, patience and

understanding this project would not have been completed. At the top of this list has

to be the patients who gave up their free time for the purposes of this trial and saw it

through to its completion. I am grateful to Mr Mark Whiteley whose ideas brought

about this project and whose advice and support (as well as proofreading) have kept

me in good stead throughout this period. I am grateful to The Whiteley Foundation for

funding myself and this project. I am greatly indebted to Judy for all her ideas and

help and for being available for many last minute “surprise” scans.

I am grateful to both Charlotte Allan and Craig Smith who spent a lot of time

following up the trial patients and collecting the data. Also Beata West, without

whose stories the office would not have been so welcoming, Judith Linton for her

organisation of the pressure monitoring patients and Mr Barrie Price for his

encouragement and permission to use his anatomical illustrations.

There was a number of hospital staff, both medical and non-medical whom have

contributed to this project. These include, Jenny Brown (in admissions who never

‘bent the rules’ for the trial patients), the anaesthetists Mike Scott and Tessa Gallagher

(for their enormous patience in theatre), sister Skilton (Cathy) and ‘Big M’ (Amanda

McCready), and Mr Gareth Tervit. I would also like to thank the team at the Post-

Graduate Medical School at University of Surrey, especially Professor R Lawrenson,

Professor R Farmer, Professor Bailey, David Lovell, Alison Sawyer, Patricia

Robertson, Alison Nightingale and Corinne Devries.

I am also grateful to the Department of Medical Physics at St George’s medical

school for their advice and input into the pressure measuring devise which was used

12

in this project. Finally I would like to thank my family for their support and

encouragement throughout this time.

13

ABBREVIATION

AQ Aberdeen QuestionnaireATV Anterior Tibial VeinA VP Ambulatory Venous PressureBMI Body Mass IndexCEAP CVI classification (Clinical Aetiology Anatomy Pathophysiology).Cl Confidence IntervalCVI Chronic Venous InsufficiencyCFV Common Femoral VeinDU Duplex UltrasoundDVT Deep Venous IncompetenceDVT Deep Venous ThrombosisFMLP Formyl-Methionyl-Leucyl-PhenylalaninFV Femoral VeinGSV Greater Saphenous VeinHIE Health Insurance ExperimentIPV Incompetent Perforator VeinHST&S High Saphenous Tie & Stripping & Multiple avulsionsNSEPSG Group randomised to Not having subfascial endoscopic perforator

surgeryPFV Profunda Femoris VeinPOV Poplital VeinPPG PhotoplethysmographyPTV Posterior Tibial VeinsRT Refilling TimeRT90 90% Refilling TimeSEPS Subfascial Endoscopic Perforator SurgerySEPSG Group randomised to subfascial endoscopic perforator surgerySF-36 Short Form 36 (Quality of life questionnaire)SSV Small Saphenous VeinSFI Sapheno Femoral IncompetenceSFJ Sapheno-Femoral JunctionTNF Tissue Necrosis FactorTRLOP Trans luminal Occlusion of PerforatorsUS Ultra SoundVV Varicose Veins

1 CHAPTER 1

1.1 INTRODUCTION

BACKGROUND

The first depiction of varicose veins is thought to be a tablet found at the foot of the

Acropolis dating from 4th century B.C. (Browse et al., 1999). Browse outlines a

thorough history of varicose veins and states the first publication on varicose veins is

thought to be the Ebers Papyrus written in 1550 BC. A section in this text describes

Tumps’ and that some types can be treated surgically, although ‘certain serpentine

windings are not to be operated upon because that would be head down’, presumably

from shock.

There are many references to veins in Hippocrates’ works who is thought to be the

first to encourage debridement and pressure dressings for the treatment of venous

ulcers. The first physicians to ligate blood vessels to control bleeding were Herophilos

and Erasistratos from the Alexandrian School of Medicine in Egypt in 270 B.C. They

also recognised that the valves of the heart stopped retrograde blood flow.

Unfortunately their works were lost when the great library in Alexandria was

destroyed.

Indian medicine developed in the same era. The main textbook, Sushruta Samhita

describes debridement of ulcers with maggots, ulcer curettage and dressing. Celsus,

the great Roman physician during the Emperorship of Tiberius (AD 14-37),

distinguished between wounds and ulcers and described ligation of veins which were

bleeding, division of veins in between ligatures and treatment of varicose veins by

15

avulsion and cauterization. He also used antiseptics on wounds and described the four

cardinal signs of inflammation. Later, Galen of Pergamum (AD 130-200) began the

description of varicose vein surgery by performing venesection for ulcers, using silk

sutures and advising the incision and tearing out of varicose veins with a blunt hook.

During the coming years multiple methods of treatment of varicose veins have been

documented along with anatomical depiction of the venous system, most famously by

Leonardo da Vinci in the sixteenth century. During this period Canano and Amatus

first described valves within veins and in 1585 Saloman Alberti published the first

drawings of valves. William Harvey’s publication of “De Motu Cordis” in 1628

began the present physiological understanding of venous function. The first

description of the term venous tone was used shortly after by Richard Lower in his

book “De Corde” (1669), and in his next publication he described the effects of limb

muscles on blood flow.

In the 18th century Reverend Stephen Hale first measured arterial and venous

pressures in live animals and Sharp in his book “A Treatise on the Operations of

Surgery”, recognised the role of gravity in venous ulcer formation. Hale went on to

describe the oedema resulting from ligation or obstruction of the major veins and

Baillie described stasis as a cause of thrombosis. The nineteenth century was a

productive period with respect to surgical knowledge. In 1822 Davis described

phlegmasia alba dolens with respect to deep venous thrombosis. Later that century

Astley Cooper stated that compression of varicose veins restored the valvular

competence and Brodie described reflux down the Greater Saphenous Vein (GSV)

and its prevention by direct pressure. Rokitansky reported the occurrence of

thrombosis at wound and inflamed sites and came close to describing Virchow’s triad

described by Virchow some eight years later. In 1854 Unna described the plaster

16

dressing for treatment of ulcers (Unna Boot). Vemeuil in his book in 1855 outlined

detailed anatomy of the veins of the leg and stated that varicose veins were caused by

incompetence of the deep veins. He also observed the valves existed in the

communicating veins which stopped blood from flowing from the deep to the

superficial system. Hilton showed that venous ulcers frequently occurred around the

medial malleolus and that rest helps healing. In 1866 John Gay in his series of

drawing from cadavers showed post thrombotic damage and mature thrombi within

the deep veins.

The modem era of varicose vein surgery began in 1891 with Trendelenberg

describing the ligation of the GSV in the upper third of the thigh to prevent reflux,

and later in the early twentieth century, Keller and Mayo described the technique of

stripping of the GSV. Homan in 1916 was the first to classify varicose veins as

primary if the deep vein was normal and secondary if the deep veins showed post

thrombotic changes.

In 1923 Berberich and Hirsch described their first attempt at phlebography using

strontium bromide and later Ratchow introduced the first water soluble contrast

medium. By 1938 Dos Santos described a clinically applicable technique of

phlebology. In 1940 Bauer used these techniques to define the state of the deep veins

in patients with Deep Venous Insufficiency (DVT). He later went on to show that the

use of heparin prevented further progression of thrombosis, and described the sequel

of DVT known as post thrombotic syndrome.

Linton in 1938 described the operation of subfascial ligation of perforator veins on the

medial lower leg communicating veins. By measuring pressures in the GSV at the

ankle Pollack and Wood showed the differences in lying and standing as well as the

drop in pressure during exercise. Cockett & Elgan Jones (1953) described ‘Ankle

17

blow-out syndrome’ and the role of the incompetent perforating veins in the

pathogenesis of this process. He also went on to outline the treatment by extra-fascial

ligation of the incompetent veins (Cockett 1955). Later in 1956, along with Dodd,

Cockett went on to publish “The Pathology and Surgery of the Veins of the Lower

Limb” which became the standard textbook at the time.

The modem treatment of varicose veins, as will be outlined later, has evolved as a

continuing process in the quest for its cure. It becomes apparent that varicose veins as

a pathological entity have been with the human race since the beginning of medical

history and continue to be a burden despite leaps in medical technology and

knowledge.

18

1.2 ANATOMY

Circumflex iliac vein

Epigastricvein Saphenofemoral

junction External pudendal

veins

Anterolateral thigh vein”

Giaccominivein

Long saphenous vein

Posterior arch vein

Calf perforator veins

Short saphenous vein

Dorsal venous arch

Figure 1 Figure showing the superficial venous anatomy (reproduced courtesy o f Mr B Price)

19

A thorough understanding of venous anatomy is essential in the treatment and

investigation of varicose veins. Although there are a large number of variations, the

venous systems within the lower limbs can broadly be divided into two, namely the

deep and the superficial system of veins. The deep fascia is a thickened fibrous layer

which forms a complete investment in the muscles and fuses with the periosteum over

subcutaneous bony points of the lower limb. The superficial system runs in the layer

superficial to the deep fascia, whereas the deep venous system lies deep to the deep

fascia of the leg. Veins which traverse this fascia and join these two systems of veins

are called Perforator Veins (PV) or communicating veins. These are also subdivided

into direct perforators, connecting the superficial veins to the deep axial veins, and

indirect perforators connecting the superficial veins to the veins and sinuses of the leg

muscles. The superficial, deep and perforator system of veins contain valves which

only allow uni-directional flow of blood. In the superficial and deep system the flow

is caudal, and in the perforating system, from the superficial to the deep veins. As will

be seen later by the use of the muscle pump and valves the veins transport blood from

the foot towards the heart.

1.2.1 Superficial Venous System of the Lower Limb

The toes on each foot are drained via dorsal digital veins which receive tributaries

from the plantar digital veins and form the dorsal metatarsal veins. These in turn unite

across the proximal metatarsal bones to form the dorsal and planter venous arch. The

medial marginal vein drains the medial aspect of the dorsal venous arch and continues

as the GSV ascending anterior to the medial malleolus. The lateral marginal vein

drains the lateral aspect of the arch and continues as the Small Saphenous Vein (SSV)

ascending posterior to the lateral malleolus (fig. 2).

20

In the sole of the foot, the superficial veins form the plantar cutaneous arch across the

root of the toes and also drain into the marginal veins. Proximal to this arch there is

the plantar cutaneous venous plexus within the fat of the heel, which also drain into

the marginal veins as well as the plantar cutaneous arch.

1.2.2 The Greater Saphenous Vein (GSV)

The GSV ascends anterior to the medial malleolus, along the postero-medial border of

tibia and within the superficial fascia accompanied by the saphenous nerve. It is at

this level that the saphenous nerve (supplying sensory fibres to the medial aspect of

the calf and the foot) can be damaged as a result of stripping of the GSV or avulsions

of varicosities. At the level of the knee the GSV arches posterior to medial plateau of

the tibia and medial condyle of femur. It then runs proximally along the medial aspect

of the thigh to join the Common Femoral Vein (CFV) at the Sapheno-Femoral

Junction (SFJ) by piercing the deep fascia of the thigh at the saphenous opening (fig

1). This aperture in the deep fascia is approximately 3cm infero-lateral to the pubic

tubercle and is called the cribriform fascia.

The GSV contains 10-20 valves (Tibbs et a l. 1992) allowing uni-directional flow of

blood towards the heart. It has important but variable number of tributaries just before

its union with the CFV, namely the superficial (and often the deep) external pudendal,

superficial epigastric vein and superficial circumflex iliac veins (Mcminn 1990).

Within the thigh the antero-lateral and postero-medial cutaneous veins drain into the

GSV.

The posterior arch vein drains a fine network around the medial malleolus and

ascends along the postero-medial aspect of the calf to join the GSV distal to the knee

joint. There are major perforating veins connecting this tributary to the posterior tibial

21

veins (PTV) lying deep to the fascia. An anterior tributary ascends along the dorsum

o f the foot often joins the GSV at the knee.

C om m unication to glu teal vein

Medial circum flex

sa p h e n o u s

Poste rio rarch vein

Perfo ra to r veins

P o s te ro 'ia te ra l vein of thigh

G iaccom ini vein

S h o rt s a p h e n o u s vein

P o ste ro -la te ra l vein

Figure 2 Figure depicting venous anatomy (reproduced by permission of Mr B Price)

1.2.3 Small saphenous vein (SSV)

The lateral marginal vein continues as the SSV behind the lateral malleolus. It ascends

lateral to the tendo-calcaneus. It then pierces the deep fascia and ascends medially

within the calf to lie in the midline ascending on the gastrocnemius muscle. It

emerges between the two heads o f gastrocnemius to terminate in the popliteal vein

typically 3-7 cm above the knee joint within the popliteal fossa. Its termination is

22

often variable and can join the popliteal vein below the knee, GSV via the antero­

lateral or postero-medial veins of the thigh or more rarely it may drain into the

femoral vein, the common femoral vein or even tributaries of the internal iliac veins.

Within the calf it ascends in proximity with the sural nerve (Gray 1995). The

Giacomini vein, is a superficial vein which, when present, connects the GSV and SSV

along the posterior aspect of the thigh.

1.2.4 Deep Venous System of the Lower Limb

The deep veins of the lower extremities, accompany the corresponding arteries (fig.

3). The plantar plexus in the planter region of the toes, give rise to the plantar digital

veins. These unite with the dorsal digital veins giving rise to the four plantar

metatarsal veins. These veins connect, via perforators, with the dorsal veins and

continue to form the plantar venous arch. Medial and lateral plantar veins

communicate with the GSV and SSV and form the PTV behind the medial malleolus.

PTVs accompany the posterior tibial artery and receive tributaries from the muscle

compartments; in particular the soleus venous plexus, the superficial veins and the

peroneal veins.

23

Inferior Vena cava ‘Aorta & common iliac arteries

Common iliac vein

External & internal iliac veins

Common femoral vein

Profunda femorisSuperficial femoral vein

Popliteal veinGastrocnemius vein

Anterior tibial vein Soleus muscle sinus

Posterior tibiai vein .Anterior tibial veinPeroneal vein

Figure 3 Deep venous anatomy (reproduced by permission o f Mr B Price)

On the Dorsum o f the foot the dorsalis pedis veins accompany the corresponding

artery, and form the paired anterior tibial veins (ATV) at the ankle. At the distal

boarder o f the popliteus muscle the ATV and PTV unite to form the popliteal vein

24

(POV). Medial and lateral Gastrocnemius veins usually drain directly into the POV.

The POV is at first medial then posterior and finally postero-lateral to the popliteal

artery as it ascends with in the popliteal fossa to the aperture within the adductor

magnus where it becomes the femoral vein (FV). This vein accompanies the

corresponding artery and travels from the postero-lateral aspect of the artery to its

medial aspect as it ascends within the adductor and femoral triangles. It receives

profunda femoris vein (PFV) to become the common femoral vein (CFV). This vein

lies within the medial compartment of the femoral sheath (in between the artery and

the femoral canal). It receives tributaries (a variable number which may also drain

into the GSV), including the GSV itself just before ascending behind the inguinal

canal as the external iliac vein.

1.2.5 Perforating Veins

There are four groups of perforating veins within the leg, namely those within the

foot, medial and lateral calf and those within the thigh (Gloviczki & Bergman, 1997,

fig. 1 & 2).

Within the foot most of the perforators have no valves and connect the superficial

veins such as the dorsal venous arch, the greater and small saphenous veins to the

dorsalis pedis or medial and lateral planter veins.

Cockett Perforators

The most important perforators are located on the medial aspect of the calf, and are

named after Cockett:

Cockett I - behind medial malleolus

25

Cockett II - 7-9cm proximal from the medial malleolus, 2-4cm from the medial edge

of the tibia.

Cockett III - 10-12cm proximal from the medial malleolus, 2-4cm from the medial

edge of the tibia (Golviczki & Bergan et a l ) .

The Cockett perforators connect the posterior arch veins (or a tributary of the GSV)

with the PTV.

Paratibial perforating veins are usually within 1 cm of medial edge of the tibia. 3

independent clusters usually exist lying 18-22cm, 23-27cm and 28-32cm from the

medial malleolus. The majority of these connect the tributaries of the GSV to the deep

veins.

Boyds perforator lies 35cm from the medial malleolus and 2cm from the tibial edge,

connecting the GSV or its tributaries to the PTV or POV.

Indirect perforators are randomly distributed mostly in the proximal calf. On the

postero-medial side of the calf indirect perforators arise from the SSV and connect

with muscular sinuses or veins which drain the gastrocnemius and soleus muscles into

the deep veins.

Peroneal perforator is a direct perforator connecting the tributaries of the SSV and

the peroneal vein (include Bassi perforator, 5-7 cm from lateral malleolus and the 12

cm perforator).

On the antero-lateral side of the calf direct perforators connect the anterior tributaries

of the GSV with the paired ATV.

26

Within the thigh there are many perforators joining the deep system to the GSV. Two

of note are groups on the medial side, the Dodd’s perforators and the Hunterian

perforators connecting the GSV with the proximal POV or the FV.

1.3 PHYSIOLOGY

The function of the venous system in the leg is to return the blood from the lower

limb to the heart. In the supine position the pressure at the level of the right atrium is

0-2 mm Hg and 15 mmHg within the foot veins. Hence there is a pressure difference

of 13-15 mmHg driving the blood back towards the heart (Browse et al..).

In the erect posture the column of blood between the heart and the foot exerts a

gravitational force which increases the pressure within the veins of the foot. This

increase in pressure is proportional to the column of blood between the right atrium

and the foot (hpg, h = height of column of fluid, p = density of the fluid and g =

gravitational acceleration). In order for the blood to return to the heart in the erect

position a “pump” is required to overcome the increased pressure on the venous side

of the leg circulation. Such physiological pumps exist and are discussed below.

Venous blood flow is directed by valves within the walls of the vein. These are

bicuspid valves made from collagen covered by endothelium. They prevent blood

from flowing away from the heart. The valves within the PV and communicating

veins prevent blood from flowing from the deep to the superficial system of veins.

This is reversed in the foot where PV valves prevent blood from draining from the

superficial veins into the deep veins within the muscles of the sole of the foot.

27

1.3.1 The Venous Wall

The wall of the veins like those of the arteries comprise of three layers (Gray 1985):

Tunica Intima - Containing a layer of endothelium, a subendothelial layer of fine

connective tissue and an elastic or fenestrated layer which forms the main bulk of this

layer.

Tunica Media - Transverse muscle layer. The thickness of arteries are mainly due to

this layer. The nervous supply to these muscles is chiefly from the sympathetic system

which form a fine plexus around the larger vessels.

Tunica Adventitia - External connective tissue coat. Vasa vasorum (nutrient vessels

arising from a branch of the artery or neighbouring vessels) penetrate this layer and

provide the vessels with a blood supply. Minute venous systems accompany these

vessels along with lymphatics and nerves.

The main difference between these layers in the arteries and veins is that there is a

comparative lack of the muscle layer and a much smaller amount of elastic tissue

within the vein walls. The veins also function as a reservoir of blood with two thirds

of the circulating blood volume within the system at rest. This volume can readily be

reduced by rapid cardiovascular reflexes, metabolites and circulating vasoactive

substances which can result in an increase in venous and arterial muscle tone. The

vein walls also have the ability to collapse when not filled with blood. In this manor

venous tone plays an important role in the distribution of blood volume, control of

body temperature and blood pressure.

28

1.3.2 Valves

The valves present in the venous system function to direct the flow of blood and are

bicuspid in structure. They comprise of reduplication of the inner coat reinforced by

connective tissue and elastic fibres and are covered by endothelium on both surfaces.

The valves are attached to the vein wall at the convex edge of their semi lunar valves.

The concave end is free and lies in close opposition to the vein wall during the correct

flow of blood. Once regurgitation occurs the valve cusps become distended their

edges are brought into contact and regurgitation interrupted (Gray 1985).

The position of these valves in the lower limbs is inconsistent. There is invariably a

valve at the proximal end of the GSV which is thought by some to be important in the

development of venous reflux (Basmajian 1952, Cotton 1961, Eger 1943). The valves

in the perforating veins of the leg (excluding the foot) are arranged to allow blood

flow from the superficial to the deep system.

1.3.3 Venous Pump

The veins within the lower limbs act as reservoir chambers whose content is pump

towards the heart by the contraction of the surrounding muscles within the lower limb.

The valves with in the veins direct the blood caudally and prevent it from falling

down towards the leg. The pumping mechanism comprises of:

29

1.3.3.1 The Foot, Calf, Thigh, Abdominal and Thoracic Pumps

The foot pump acts to expel blood with in the venous vessels within the foot. The

tightening of the plantar aponeurosis and coordinated contraction of the foot muscles

in conjunction with slight changes in the position of the foot arches result in ejection

of venous blood proximally into the leg, via the superficial and deep system of veins.

The soleal sinuses and gastrocnemius veins are intra-muscular venous sinuses and the

posterior tibial, anterior tibial and the peroneal veins lie in between these muscles

(inter-muscular). These inter-muscular veins are not subjected to as higher pressures

as the intra-muscular veins and hence act as the outflow tract for the foot veins during

walking. All these veins join up to form the main exit point of the calf pump, the

popliteal vein. As this vein ascends within the subsartorial canal in the thigh it is

protected from pressure produced by thigh muscle contraction. It then ascends into the

abdomen and later the thorax, and is subjected to intermittent positive and negative

pressures produced by respiration.

The superficial system does contribute to the pumping mechanism as it is squeezed

against the skin during muscular contractions. As these pressures are lower than the

deep compartments, the valves ensure that blood within this system flows up the GSV

veins into the femoral and popliteal veins or directed into the deep system via the PV.

As well as the named communicating veins there are many unnamed vessels which

drain blood into the veins deep to the fascia. The valves within these veins are

arranged so that flow from the deep to the superficial system is not permitted under

normal conditions.

When the muscles within the deep compartment of the leg contract the pressure

within the intramuscular veins reaches in the region of 200-300 mmHg. The pressure

within the intermuscular veins rises to 100-150mmHg (Browse et al. 1999). The flow

from the deep to the superficial veins is prevented by closure of the valves and blood

is hence directed towards the outflow tract.

During the phase of relaxation of the calf muscles blood then flows from the

superficial to the deep system (Bjordal 1970). At the moment when the calf muscles

begin to relax the deep veins are collapsed and unfilled by the arterial flow. The

superficial veins meanwhile are full and subject to hydrostatic pressure plus the

remnant of cardiac generated pressure, the ‘vis a tergo’. The pressure difference

between the two systems is hence in the order of 100-110 mmHg, enabling flow from

the superficial to the deep system. This reduction in volume in the superficial system

is associated with a reduction in pressure within these veins (Beecher et a l. 1936) and

the venous pressure of the foot which is essential for preservation of healthy skin and

subcutaneous tissues. The absence of this mechanism is thought to be responsible for

venous pathology.

During inspiration the diaphragm is flattened and the intrabdominal pressure is

increased and obstructs venous return. Simultaneously the intrathoracic pressure

decreases encouraging venous return from abdomen into the thorax. Once the

inspiration phase is over the intrabdominal pressure decreases and the venous return

from the limbs recommences.

Changes in the volume of the limb during exercise (venous pump function) can be

assessed, by a variety of investigations (Photoplethysmography (PPG), air and strain

gauge plethysmography and foot Volumetry) and an assessment of the efficacy of the

pump function made. The ‘gold standard’ in the assessment of calf pump function is

foot vein pressure monitoring or ambulatory venous pressure monitoring (Nicolaides

et a l. 1981). This is an invasive procedure and is not used as a diagnostic tool.

31

However it has been used to validate other non invasive tests mentioned above as will

be discussed below.

1.3.4 Failure of Pump

The failure of the venous pump can arise as a result of two broad factors which can

co-exist. Musculo-skeletal failure results from pathology affecting the contraction of

the muscles and movement of the joints of the lower limb. The normal articulation

and contraction of these muscles and joints are essential to the normal function of the

venous pump and their failure can result in venous hypertension and Chronic Venous

Hypertension (CVI) (e.g. disuse atrophy, neurological damage, vascular insufficiency,

joint disease etc).

The failure of the venous valves, be it primary or secondary, is the other factor which

in the long run can lead to venous hypertension, as a result of continuous reflux of

blood.

32

1.4 AETIOLOGY

Venous insufficiency has been broadly divided into three types, i.e. Congenital,

Primary and Secondary. The fundamental deficiency in all of these however is that of

failure of venous valves.

1.4.1 Congenital Venous Insufficiency

These are very rare conditions ranging from aplasia to rudimentary non functioning

valves.

1.4.2 Primary Venous Insufficiency

The aetiology of primary venous insufficiency remains an area of intense research and

discussion. It has not as yet been conclusively proven whether it is the valves which

primarily fail leading to vein wall failure or primary vein wall failure leading to

secondary valve failure. Trendelenburg suggested that the venous valves protect the

distal vein wall from the hydrostatic pressure of the veins above. He believed that

varicose veins began when the highest valve in the GSV became incompetent.

However this suggestion is now disputed due to the discovery of varicosities within

the tributaries of the GSV without evidence of GSV incompetence (Abu-own et al.

1994) leading to the ascending theory discussed later in this chapter. Also the early

dilations seen in varicosities were found to be distal to the valves as opposed to

proximal making their position difficult to explain by the theory of ‘back pressure’

(King 1950, Cotton 1961).

There are many predisposing factors associated with varicose veins. These include

age, sex, race, weight, height, pregnancy, diet, bowel habits, occupation, heredity,

33

alcohol, clothing and erect stance. The Basle study (Widmer 1978) showed a steady

increase in prevalence with age in apparently healthy people. Other studies have

confirmed these finding (Coon et al 1973). With regards to gender, Callam (1994) in

his review of epidemiology of varicose veins found there to be a clear female

predominance in the prevalence of varicose veins with a female to male ratio of

between 1.5:1 and 3.5:1, depending on the definition of varicose veins used.

With respect to race and geographic location there is limited good evidence to make a

conclusion. However Callam cites the first direct comparison in the United States

National Health Survey of 1961, which states that 24.1% of the whites complained of

varicose veins versus 10.4 of the blacks. This was a questionnaire survey and may be

very subjective. In another study (Mekky et al 1969), questionnaires were sent to 500

women cotton wool workers in Egypt and England who were also examined. Of the

English women, 32.1% varicose veins versus 5.8% of the Egyptian women. Callam

also quotes a more recent study performed by Maffei in Brazil (Maffei et al 1986).

This also showed a higher prevalence of varicose veins in the white (49%) versus the

non-white (36%) race.

Pregnancy has also been shown to have an impact on the development of varicose

veins. This was seen by Beaglehole etal. (1976) looking at Maoris and Pakehas in a

New Zealand population and also by Maffei looking at the Brazilian population.

Beaglehole found that females with varicose veins had a greater parity than those

without varicose veins and also the severity of the varicose veins increased with

parity. Maffei found a clear correlation between prevalence of varicose veins and

number of pregnancies. However Coon’s and also the Basle study failed to show the

same findings. It is thought that the changing hormonal milieu is causing venous

distension of veins, as well as the compression of the iliac vessels by the enlarging

34

uterus, may be responsible for increased incidence of Varicose veins (VV) after

pregnancy.

Obesity has been consistently shown to be a risk factor in the development of varicose

veins (Sadick 1992, Abramson etal. 1992). A high body mass index (BMI) is found to

be a more important risk factor in Women than in Men. A strong case for genetic

predisposition can also be made. The risk of developing varicose veins was found to

be higher in those with affected first degree relatives. Gundersen and Hague (1969)

showed that the proportion of patients with varicose veins that had a relative with

varicose veins was higher than the general population (females 43%, males 19%).

Comu-Thenard etal. (1994) examined the first degree relatives of patients with

varicose veins and compared them to a control group. He found a 90% risk of

developing the condition if both parents had varicose veins, 25% for males and 62%

for females if one parent was affected. Browse et a l. (1999) considers occupation,

posture and clothing as secondary aetiological factors and sites papers by Santler et

al, who studied policemen with varicose veins, and Lake et al who surveyed a

department store in New York, as two epidemiological studies which found a higher

incidence of varicose veins in occupations which involved standing.

1.4.3 Secondary Venous Insufficiency

Secondary varicose veins are due to post-thrombotic damage, pelvic tumours,

pregnancy, and acquired or congenital arterio-venous fistulae. In the post-thrombotic

syndrome the sequel of thrombosis in the deep or superficial system may manifest as

persistent venous hypertension (persistent exposure of the veins of the leg to increased

pressures as a result of venous pump failure, Belcarogr al. 1995). This may be due to

35

continued chronic reflux or obstruction to the venous outflow. This is commonly also

referred to as Secondary venous insufficiency.

1.4.4 CEAP Classification

In 1995, under the auspices of the American venous forum, the International

Consensus Conference on chronic venous disease developed the C (Cause) E

(Aetiology) A (Anatomical Distribution) P (Pathophysiological dysfunction)

classification of venous disease (Reporting standards in venous disease: an update

1995). This largely replaced the clinical class 0-3 (Reporting standards in venous

disease 1988).The later classification concentrated on anatomy and clinical severity as

follows:

Class 0 Asymptomatic

Class 1 Mild CVI with mild to moderate ankle oedema, mild discomfort,

usually superficial veins only.

Class2 Moderate CVI with hyper-pigmentation of gaiter area, moderate

fibrosis, without ulceration.

Class 3 Severe CVI with chronic leg pain, pre-ulcerative skin changes, eczema,

severe oedema, usual involvement of deep venous system.

The CEAP classification was designed in order for there to be a means by which to

standardise patients with varicose veins and accurately compare limbs involved in

medical and surgical trials.

Clinical Classification (CO-6)

There are seven categories in this aspect of classifying each limb. These are

Class 0 No visible or palpable signs of venous disease

36

Class 1 Telangiectases, reticular veins, malleolar flare.

Class 2 Varicose veins

Class 3 Oedema without skin changes

Class 4 Skin changes due to venous disease (Pigmentation, venous eczema,

lipodermatosclerosis)

Class 5 Skin changes as per class 4 plus healed ulcer

Class 6 As per class 5 plus active ulceration

Aetiological Classification (Ec, Ep, Es)

As described earlier venous dysfunction can be Primary (Ep), Secondary (Es) or

Congenital (Ec).

Anatomical Classification (As, Ad, Ap)

The anatomical classification involves the division of sight of reflux into Superficial

(As), Deep ( Ad) and Perforator ( Ap).

Pathophysiological Classification (Pr,Po)

The pathological cause of venous disease may be as a result of obstruction to outflow,

reflux disease or both. A multitude of tests exist to distinguish between these two

pathological process (Porter et al. 1995).

37

1.5 PATHOGENESIS

The number of theories put forward to explain the development of varicose veins and

their consequences such as fascio-cutaneous changes, goes some way to show that

varicose veins are probably multifactorial in origin.

1.5.1 Primary Varicose veins

There are two opposing schools of thoughts with regard to pathogenesis of varicose

veins. The first is that the primary failure is that of the vein wall leading to valvular

failure. The second is that primary vein valve failure leads to secondary wall changes

and failure.

With the failure of the vein wall the valve cusps become disturbed and incompetent.

Cotton (1961) and King (1950) have shown that the dilation of the vein wall starts

distal to valves and hence unlikely to be as a result of backpressure from failing

valves. There is also evidence showing that the elasticity of vein walls are reduced in

varicose vein walls compared to normal limbs. Clark et al. used simultaneous

measurement of calf volume changes (using occlusive plethysmography) and dorsal

foot pressures to calculate and elastic modulus (K):

APK= -----------

AVWo

There also appears to be reduced elasticity within the vein walls of patients at high

risk of developing varicose veins (history of factors strongly associated with varicose

veins such as family history, standing occupation etc.) than normal legs (Clark et al

38

1989, Clarke et al 1992). Clarke et al. go on to suggest that this loss in elasticity

precedes the development of varicose veins and has a role in its development.

Rose and Ahmed (1986) noted an increase in amount of abnormal collagen fibres in

the structure of varicose vein walls. They have suggested that what happens at a

cellular level in the development of varicose veins, is an imbalance between collagen,

muscle cell and elastic fibre, resulting in a loss of contractility. Venturi et al. (1996)

using markers for collagen and elastin found that the dilations of varicose veins were

directly related to the decrease in elastin content of the vein wall in these areas. They

also found that non-dilated areas of the same veins had normal structure within their

walls. They however did not find a significant difference in the collagen content of

varicose veins as compared to normal vein walls. They concluded that the dilation of

the veins were related to a reduced synthesis or accelerated catabolism of elastin.

Further support for the hypothesis that biochemical and functional abnormalities

develop with in the vein wall came from Lowell et al. (1992) and Barber et al (1997).

Lowell et al submerged venous rings in organ chambers and observed their

contractility in response to various stimulants (potassium chloride, endothelin

(endothelium derived contraction factor) and noradrenaline). They found reduced

contractility of rings of varicose vein removed from patients with varicose veins when

compared against normal vein segments (normal excess segments used in bypass

surgery). Barber et al supported this by showing that varicose vein walls had reduced

contraction to endothelin-1 as opposed to normal vein wall. They also found a

reduction in the number of endothelin-B receptors (receptor for an endothelial derived

contracting factor) on varicose vein endothelium, corresponding to the reduced

contractile response. They suggest that the increase in levels of endothelin-1 could

account for the down regulation of the endothelin-B receptors.

39

Primary valvular defects are thought to be due to abnormalities in the structure of the

venous valves. Ludbrook (1986) suggested the failure of one valve owing to high

pressure from above may cause the valve to become overloaded and damaged with

continued damage of the valves below. He had already shown that proximal

incompetence of valves preceded the changes seen in varicose veins (Ludbrook 1963).

However he was unable to ascertain whether it was the inherent defect in the vein

wall that led to the valves becoming incompetent or a primary defect within the

valves.

Corcos et a lls (2000) histological work into defective valves showed that the

development of primary venous insufficiency was due to structural changed in the

valves which included dilation of the annulus and hypertrophy of the cusps.

Boisseau (1997) in his paper explains that valvular sinuses allow vortices to be

created with in them. The blood moves slowly here and under normal condition of

movement these empty rapidly. Conditions of hyper-viscosity and stasis result in

deposition of red cell aggregates and leukocytes. These are hypoxic areas which cause

endothelium activation and damage and the adherence fibrin-leukocyte nidus and

thickening of the sub-endothelial layers which become thrombogenic. Subsequently

the coagulation system is activated resulting in thrombin formation and ultimately

incompetent valves which cause skin venous hypertension. This role is important in

deep vein thrombosis but its role in Chronic Venous Insufficiency (CVI, prolonged

venous hypertension) is uncertain.

1.5.2 Descending Theory

Trendelenburg having introduced high saphenous tie as the surgical treatment of

varicose veins, suggested that the venous valves served to protect the vein wall below

40

it from the hydrostatic pressures of the column of blood proximal to it. He believed

that once the highest valve in the GSV gave way, the increased pressure burden led to

varicosities, and hence suggested ligation of the SFJ.

Ludbrook (1963) measured static and dynamic venous pressure at different levels

within the GSV in patients with severe varicose veins, mild varicose veins and normal

subjects. He found that valvular incompetence preceded the changes associated with

varicose veins. He concluded from this that the incompetence of the SFJ preceded

development of distal varicosities.

1.5.3 Ascending Theory

The descending theory of valvular incompetence in the pathogenesis of varicose veins

began to be questioned as a result of high recurrences following high saphenous tie as

suggested by Trendelenburg. Furthermore, cadaveric anatomical studies in non-

varicose vein subjects have shown that in 20-40% there is an absence of valve in and

above the common femoral vein and yet no varicose veins had developed. Further

work has shown there to be no correlation between the absence of this valve and GSV

incompetence (Basmajian 1952, Eger & Casper 1943, Powell & Lynn 1951).

Cotton (1961) in his anatomical study of normal cadaveric GSV veins and veins

stripped at surgery, found that varicosities did not occur below the terminal valve

(Most proximal valve nearest to SFJ), but most commonly found below the sub

terminal valve. He also noted the presence of varicosities further down the leg in

some 9 out of 40 of operated patients in the absence of a saphenous varix. He found

difficulty in explaining the lack of varices below the terminal valve in the early stages

of varicose veins but does suggest that the development of varicose veins may not be

41

solely due to the effect of increased pressure on the wall or that if the sapheno-

femoral valve is the last to become incompetent it appears to have been affected least.

Alexander’s (1972) stated that analytical study which reviewed the evidence for the

descending theory left him wanting, as the evidence which he submitted was

inconsistent or opposed the basis on which the descending theory was based.

A large series of patients (500 limbs) referred for cosmetic leg veins were scanned by

Thibault et al. (1990). They were divided into four groups on clinical assessment:

-Spider veins only

-Varicose veins only

-A combination of above

-Clinically normal

They found the incidence of below knee GSV reflux to be the highest and the

incidence of SFJ incompetence to be the lowest in all four groups, which stands

against the descending theory.

In order for the descending theory to be acceptable the ligation of incompetent SFJ

must result in abolition of reflux within the GSV or prevention of further varices from

developing. However Mcmullin Etal (1991) showed that ligation of the SFJ without

stripping of the GSV failed to control reflux in the GSV in just over 50% of their

patients (24/52). Lofgren et al. (1957) published their operative findings in 510

recurrent varicose veins. Of the 488 recurrence associated with the GSV, 197 of them

had had adequate ligation of the SFJ previously and yet in all of these patients reflux

persisted in the remaining GSV. As the GSV had been treated by sclerotherapy

following the original ligation, the GSV was found to have recanalized up to the

upper third of the thigh or higher. They found that despite SFJ ligation the

recanalisation progressed from distal to proximal. In patients with inadequate SFJ

42

ligation at the first operation the recanalisation was observed in both proximal and

distal directions.

Further more, a number of studies have shown a refluxing GSV in the absence of SFJ

incompetence (Abu-Own etal 1994, Labropoulos et al. 1994, 1997). Abu-Own et al.

having noted the relatively common occurrence of this finding performed Duplex

Ultrasound (DU) on 167 consecutive patients referred to them. They found that in a

third of patients with GSV reflux the SFJ was competent. In most cases they could not

attribute this to Incompetent Perforator Vein (IPV) as only 5 limbs showed IPV. They

have surmised that the function of the valves may be to protect the capillary and

venuole systems from large fluctuations in pressure and that valvular failure may start

distally and progress proximally.

Jutley et al. (2001) reviewed their Duplex Ultrasound (DU) results on 223 limbs

referred to their vascular laboratory with primary uncomplicated varicose veins. They

found 30% of these patients to have an intact SFJ despite signs of varicosities. The

majority of these were caused by IPV with in the thigh and the calf. These findings

have also been shown by Singh et al. (1997, 52% with varicosities and competent

SFJ) and Somjen (1995, 34% with segmental reflux in GSV with competent SFJ).

Labropoulus et al (1994) correlated the anatomical extent of reflux with clinical signs

of patients with superficial venous insufficiency. He also found that in 123 patients

with reflux confined to the GSV, 40% had an intact SFJ. The group also found that

patients with segmental below knee reflux were symptomatic of disease with

significantly higher rates of aching swelling and skin changes. The group went on in

1997 to perform DU on three groups of patients which they felt represented the

progressive nature of the disease. These groups were those with no symptoms, with

prominent veins but no varicosity, and those with varicose veins. They found reflux in

43

the below knee GSV to be the most common finding (68%) in all three groups, and

only a third of the limbs with above Knee GSV reflux had SFJ incompetence.

They also showed multi-segmental reflux within the limbs of the lower limb which is

not explained by the descending valve failure theory and the fact that distal reflux was

more common in all groups again pointed towards an ascending progression of

disease. They also suggest that the calf pump function, duration of symptoms, extent

of disease, pattern and amount of reflux to be influencing factors in disease

progression since the prevalence of distal reflux was similar in all three groups. They

go on to site functional, morphological and biochemical studies which show

segmental venous wall damage irrespective of position of the valves. Seidle et al.

(2004) also suggested that Labropoulos’s theory had some merit since in a group of

1712 patients attending a clinical for mostly cosmetic varicose veins, 43% (735) had a

competent saphenous system.

Descending valvular failure, as suggested by Trendelenburg, does not account for

many cases of varicose veins. Also the recurrence rate following a high tie negates the

descending valvular theory. There appears to be other mechanisms at work which

may account for surgical failure and recurrence following treatment based descending

theory of pathogenesis.

1.5.4 Fascio-cutaneous Changes

Fascio-cutaneous changes are seen in CVI with severe calf pump dysfunction. The

changes seen within the legs range from dermatitis, venous ‘stars’ and dilation, hyper­

pigmentation, oedema, lipodermatosclerosis, skin atrophy and finally ulceration.

These changes are more commonly seen within the gaiter area of the legs. Intra-

dermal venules become dilated under increased pressure and become fine dilated

44

veins prone to localised thrombosis. They are most commonly found around the

medial malleolus where they are referred to as ankle flare (Browse 1983).

Pigmentation around the gaiter region is as a result of haemosiderin laid down by red

blood cells which have been extruded through the inter-endothelial pores.

Lipodermatosclerosis describes the progressive fibrosis of the skin and subcutaneous

tissues induced by the high venous pressures (Browse 1983). In its chronic state the

skin around the gaiter area becomes contracted with oedema above it and is refereed

to as the ‘Inverted champagne bottle shape. All the signs described occur as a result of

impaired tissue nutrition and oxygenation, which ultimately may lead to ulceration,

often following innocent trauma to the gaiter area.

1.6 EPIDEMIOLOGY

The true epidemiology of venous disorders cannot be accurately assessed. This is due

to the wide variation of the disease and a lack of uniformity of definitions,

classification, and investigation along with lack of standardised diagnostic criteria.

Callam (1994) in his review of the epidemiology of varicose veins attempts to pay

particular attention to these variables and points out the differing variables of the

studies which he reviews.

1.6.1 Varicose Veins

Galium estimates the prevalence of visible tortuous varicose veins in an unselected

population of westerners over the age of 15 to be 10-15% in the male, and 20-25% in

the female. In the Framingham study, 1720 men and 2106 women free of varicose

45

veins were followed up for a 16 year period. The two year incidence was on average

39/1000 in men and 52/1000 in females. The incidence was higher in women than

men in all age groups except 80-89 (Brand et al 1988, Debacker 1977). Age had no

significance effect on the incidence in each sex, unlike the community survey carried

out by Abramson et al. (1981). He found the incidence of varicose veins in a

community in western Jerusalem to be 10% for men and 29% in women and they both

rose with increasing age.

In Basle Study III, the prevalence of all grades of varicosity in a sub-population of

healthy Swiss workers was 56% in men and 55% in women. Twenty percent of the

men and eleven percent of the women had trunk varices (Widmer 1978).

In a study by Maffei et al. (1986) the prevalence of varicose veins in a population of

1755 Brazilians, was 47.6%. He also showed a female preponderance. Beaglehole

(1976) found the prevalence of varicose veins to be 36.3 % in the male and 47.4 % in

the female Maoris in New Zealand, and 21.6% and 40.4 % in the Pekehas race.

The Edinburgh Vein study is a cross sectional survey with a target population of 18-

64 years old. The participants were an age stratified random sample selected from the

computerised age-sex register of 12 general practices. Of the 1566 people examined,

age adjusted prevalence of trunk varices in this Edinburgh population was found to be

39.7% in Men and 32.2% in women in the age group of 18 to 64. In contrast to the

Widmer, they found trunk varices to be more common in men than women (33.3 %

versus 26.2 %). They also found that 80% of the 1566 of the random sample of people

they examined, had hyphen web and reticular varices (Evans 1999).

Overall it would appear that varicose veins are more prevalent in females than males

in most studies. The incidence with increasing age increased in one study and the

46

Framingham study found the incidence of varicose veins to be 39/1000 in men and

52/100 in women.

1.6.2 Fascio-cutaneous Changes

Fascio-cutaneous changes are seen most commonly around the gaiter region and are

the long term sequel of CVI. These changes include oedema, hyper-pigmentation,

dermatitis and weeping eczema, lipodermatosclerosis and ultimately ulceration.

Most of the published studies do not quote the prevalence of fascio-cutaneous

changes. Callam (1992) in his review of prevalence of leg ulceration concludes that

approximately 1% of the population are likely to have had leg ulceration but only 0.1-

0.2% are open ulcers at a single point in time. Coon et al. (1973) found the incidence

of these leg changes in the Tecumseh community to be 3% in men and 3.7% in

women, rising to as high as 20% in the over 70 year olds. In the Brazilian study by

Maffei, the prevalence of active or healed ulcer was 3.2% in men and 4% in women.

In the Basle III study, 15% of subjects had CVI with no prevalence for men over

women. However the age adjusted prevalence of CVI was 9.4% in men and 6.6% in

women in the Edinburgh vein study. In this study gender differences were not found

to be statistically significant when the grades of severity were analysed individually.

1.6.3 Primary and Chronic Venous Insufficiency

In all the studies carried out on the epidemiology of varicose veins, none differentiates

between primary and secondary varicose veins. Therefore no accurate data exists with

respect to quantify the relative contributions of the two pathologies.

47

1.7 INVESTIGATIONS OF VEINS

Accurate investigation and diagnosis are the basis of medical treatment. Confirming

the correct clinical suspicion is essential in planning treatment of venous disorders.

Venous examination alone is unreliable in accurately diagnosing venous reflux and

anatomy (Hoar et al. 1984, Singh et al. 1997). The correct anatomical mapping of the

vascular system is vital to these treatments and a number of different investigations

fulfil this need. The available modes of investigation provide functional as well as

anatomical information which help to confirm the clinical suspicion and plan

treatment. However none of the available diagnostic tools provide complete

information. It is important to know for each test which part of the venous anatomy

and function it measures and its accuracy.

The ideal investigation must have a high accuracy, sensitivity, specificity and positive

and negative predictive values. It should be non-invasive, reproducible and practical,

enabling it to give the maximum amount of information with regards to anatomy and

function of the venous system. This information would allow a clinician to plan his

treatment effectively. Since no such tests exist at present, one often has to rely on

more than one investigation for the accurate picture.

1.7.1 Investigation of Venous Anatomy

Not all the investigations mentioned here have stood the test of time or are in

everyday use but they are included for completeness.

48

1.7.1.1 Phlebography

1.7.1.1,1 Ascending Phlebography

Investigators in the past have thought ascending phlebography to be the best standard

against which other new method of investigation of lower limb venous reflux should

be measured (Baker et al. 1993, Lea Thomas & Bowles 1986).

This process involves the use of x-ray contrast medium to delineate the area of

interest. It is an invasive form of investigation which has become safer by the

introduction of low osmolality contrast medium (Browse et al. 1999).

In the lower limb, a vein within the foot is cannulated and a tourniquet applied

proximally depending on the area of interest. In order to observe the deep venous

system the tourniquet is often used to occlude the superficial venous system at the

ankle and also above the knee, without disrupting the arterial flow. If the superficial

system is not occluded by a tourniquet, a confusing picture may ensue making any

interpretation difficult. Under screening, contrast medium is then injected in to the

foot vein. Films from various angles are taken from the foot to lower inferior vena

cava. Valsalva manoeuvres distend the veins and assist in assessing valve function.

Manual calf compression, simulate the calf pump and assessment of outflow can be

made as well as outlining IPV. Tilting beds and valsalva manoeuvres are also used to

delay venous emptying allowing better visualisation and assessment of deep vein

incompetent valves. By placing a radiopaque ruler on the table, an assessment of the

position of the perforator can be made. However with the advent of duplex

ultrasonography deficiencies in this test have been shown, in particular with respect to

identification of segmental reflux.

49

1.7.1.1.2 Varicography

The direct injection of contrast media into a varicosity can outline the superficial

system involved as well as communication of the varicosity with the deep system.

With the examining table in the foot down position, the contrast is injected. The dense

contrast medium then enters the leg and any incompetent perforators lower down. The

table is then flattened and radiographs taken of the superficial system before the table

is placed in head down position. This allows the contrast medium to travel to the groin

and images are taken of the SFJ. Again by the use of a radiopaque ruler one can

estimate the position of these communications. However, due to the fact that the

contrast is travelling from the superficial system into the deep, no assessment of the

valvular function is usually possible. Therefore an assessment is made as to whether

the communications seen are abnormal in architecture (tortuous, dilated veins, usually

> 3mm, which do not taper distally. Browse et al. 1999, Lea Thomas & Keeling

1986).

This invasive investigation is dependent on the pathway taken by contrast media and

may possibly miss abnormal communications, such as IPV.

1,7.1.1.3 Saphenography

Saphenography is used to outline the GSV and SSV usually before use as grafts in

cardiac bypass procedure. The procedure is similar to ascending phlebography, but

the GSV is cannulated if possible and no tourniquets are applied. By manual

compression of the popliteal vein along with tilting of the table the whole of the GSV

can be visualised. This test has now been replaced by non invasive duplex ultrasound

50

mapping, which is non-invasive, does not involve ionizing radiation and can clearly

show defects with in the walls of the vessels.

1.7,1.1.4 Descending Phlebography

This procedure is used to assess retrograde flow within the lower limbs. The femoral

vein is cannulated and contrast injected in the supine position while the patient

performs valsalva manoeuvres. The contrast will be seen descending down

incompetent valves, and the lowest level of reflux can be used to grade the reflux (0-

4). An assessment of the sapheno femoral incompetence and the GSV can also be

made since any reflux of medium into this vein is abnormal. However as has been

discussed in ascending theory of varicose veins (Pathogenesis), the SFJ and proximal

valves in legs affected by varicose veins may be competent with reflux and

malfunctioning valves more distally. Clearly this procedure has its deficiencies and

has been replaced by DU.

1.7.1.1.5 Complications of Phlebography

Phlebography is an invasive technique and carries complications related to the

contrast medium used:

The use of non-ionic low osmolar contrast medium has reduced the systemic and

idiosyncratic reactions observed with earlier contrast media. According to Browse et

al. up to 5% do suffer with mild systemic upsets such as nausea and vomiting. Severe

reactions such as bronchospasm, and severe systemic anaphylaxis are rare and require

intensive resuscitation. Local complications of the effect of the contrast media include

51

local pain, thrombophlebitis, chemical cellulites in cases of extravasation of the

media.

Non contrast related complications concern the technique used. This includes air

embolus pulmonary embolus and arterio-venous fistula. Also the radiation exposure

of the patient during the procedure needs to be considered.

The complications and disadvantages noted above are all overcome by colour duplex

imaging, which is non invasive with no side affects and gives both an anatomical map

and a functional assessment of the venous system.

1.7.1.2 Ultrasound (US)

Ultrasound allows non invasive assessment of patients with venous and arterial

disease. Austrian physicist Christian Doppler (1805-1853) described the Doppler

effect of sound waves. Essentially he showed that the frequency of sound emitted by a

moving object increases on approaching a subject and decreases on moving away.

This principle is applied to observation of moving blood within a vessel and the

changes in frequency converted to audible or visual outputs of choice (sound or

graphical). The frequency shift is expressed as:

2Fo X V X COS0

AF = -----------------

Where:F = Frequency shiftC/Fo = Wavelength of ultrasoundV Cos0 = Closing speed between the erythrocytes and the Doppler probe.(Bernstein 1993)

The US apparatus fundamentally consists of a piezoelectric crystal which acts as the

source of the sound wave, and a second crystal which acts as receptor of sound waves

52

reflected off the surface of blood vessels. These crystals convert pressure waves into

electric signals, and electric signals into mechanical vibrations. In this way they act as

both transmitter and receptor of ultrasonic sound. The frequency of the sound waves

emitted by the crystal within the probe is determined by the number of oscillations per

second of the source. Diagnostic ultrasound for medical purposes uses frequencies in

the 1-20 MHz range, which can be varied depending on the indication for the test.

The velocity of ultrasound in tissue determines the travel time between the transducer

and the moving blood vessels. Continuous wave ultrasound isonates everything with

in the path of the beam and does not determine the site of moving cells. However

when the sound is transmitted in bursts (pulsed, or gated) the site of from which sound

is reflected can be determined since the speed of sound in the tissue is known and the

time interval can be calculated:

PRF = C/2d

Where:PRF = Pulse repetition frequency C = velocity of sound in tissue d = distant to reflector

Greyscale or B-mode US is another application of the use of US. This does not look at

moving particles with in the tissue but provides a virtual image of the region under

examination by analysis of the backscatter or echoes from the interfaces in the tissues

of differing echogenecity (different amplitudes of reflected sound). These reflected

waves are of differing intensity and are transformed in to images; black representing

absent signals, white strong signals and shades of grey for the intermediate signals. In

this way an virtual two dimensional image can be created. Real-time applications of

B-mode (real time US or two dimensional echo) allows assessment of both anatomy

53

and motion by rapid generation of static images (15-60 per second) which produces

the impression of motion.

1.7.1.2.1 Real Time Ultrasound (two dimensional echo)

This system produces a virtual image of the region under examination. This type of

probe (2 MHz) enables analysis of the structure of the tissues of differing

echogenicity. Augmented by the use of colour, it can produce virtual images of

interested areas.

1.7.1.2.2 Duplex Ultrasound

In this system a pulse wave Doppler system is combined with a B-mode system to

produce real time images and motion in combination (fig. 4, 5). This allows study of

the vessels and haemodynamic properties using Doppler and visualisation of the

vessels and anatomy by the B-mode. This examination is improved by the use of

colour to represent the blood moving away or towards the probe (Doppler shifts for

each pixel represented as red and blue depending on whether the shift is due to the

blood moving away or towards the probe). Also the intensity of the colour represents

the velocity of the moving blood. This form of imaging is known as colour duplex or

Triplex.

Colour duplex does have its limitations. The simultaneous two dimensional images

produced are of a poorer quality than echography mode alone. The optimal angle of

the beams differ for that of echography and Doppler and rapid movement of the probe

can cause colour interference. A further development. Power colour duplex which

54

assesses the perfusion and not direction of flow (usually depicted as orange colour)

and is also particularly useful in outlining lesions with the vessel wall.

1.7.1,2.3 Choice of Frequency

The probes used in us examinations contain different piezoelectric crystals which emit

differing frequencies of ultrasound. The frequency used in each examination is

determined by the depth and diameter of the vessel to be studied along with the

experience of the examiner. Low frequency probes (2 MHz) are used for deeper

vessels e.g. Large abdominal vessels, but are also useful in obese patients. Higher

frequency probes (5-7.5 MHz) are used to study veins with a diameter of 2 mm. The

large frequency probes (up to 12MHz) enable very superficial and smaller vessels to

be studied. Larger frequencies are used to study reticular veins within the skin

(20MHz).

55

MATERIAL REDACTED AT REQUEST OF UNIVERSITY

1.7.1.3 Investigation of Choice

Despite its shortcomings, Venography had been the investigation of choice and the

gold standard to which other modalities are compared (Baker et al. 1993, Lea Thomas

& Bowles 1985, Hanrahan et al. 1991, Herman RJ et al. 1980, Meyer et al. 2000,

Neglen & Raju 1992).

With the advent of improving technology and development of US, phlebography has

been displaced as the investigation of choice due to its invasive nature and its

shortcomings. However in order for US investigation to be useful it has to be accurate

and reproducible and compare well with established ‘Gold standards’, however poor

this method of assessment may be. A number of studies have compared the different

56

modalities as well as comparing their findings with operative findings which have

been used as the gold standard in some studies.

Valentin et a l (1993) in their prospective study compared the venographic (ascending

and descending phlebography) findings with DU finding in 23 limbs with CVI. These

findings were assessed against the patient’s clinical findings. They found DU to be

more accurate in explaining the clinical findings than venography. Descending

venography only showed venous disease in 39% (increased to 94% with the addition

of Ascending venography) of patients with obvious varices and venous ulceration,

whereas DU had a sensitivity of 95%. Other studies have confirmed such poor finding

with descending venography (Ackroyd et a/.(1986) 31% in proven post thrombotic

damage and 19% of patients with lipodermatosclerosis, Herman et al. (1980) 36% and

38% respectively, Neglen & Raju (1992) 17% and 21% with corresponding DU

findings being 56% and 79%). An explanation for these findings may be the presence

of a competent valve in the proximal part of the femoral vein making evaluation of

the distal part of the vein difficult.

Baker et al. (1993) compared DU with descending phlebography in 79 limbs with

venous abnormality on ascending Phlebography (23 with post thrombotic changes) as

well as foot volume plethysmography. They found good agreement between the DU

and ascending venography with respect to deep vein reflux. The half refilling time

correlated well with the DU findings but not with descending phlebography. As

descending phlebography can only detect refiux distal to the first competent valve, it

did not detect segmental refiux below a competent valve in 12 patients which were

detected duplex scanning. Since 11 out of these twelve patients had post-thrombotic

damage on ascending venography or abnormal foot volumetry, these were assumed to

be pathological refluxes missed by descending phlebography. Duplex was also found

57

to be more sensitive in detecting reflux in the deep and superficial system below the

knee.

Phillips et al. (1995) showed DU to be as accurate as ascending venography and

Varicography in assessment of sapheno-femoral and sapheno-popliteal junctions, but

did cast a doubt on the ability of duplex to assess IPV (Phillips & cheng 1996) as will

be discussed below.

In 1989 Van Bemmelen et al. described the quantitative segmental evaluation of

venous reflux with duplex ultrasound scanning. They used rapidly deflating

pneumatic cuffs to simulate venous haemodynamics and measured venous reflux

times and velocities in normal subjects. They found the deflation of the distal cuff

(calf) was the only method that allowed reproducible quantitative measure of reflux to

be assessed in all segments of lower limb. Neglen & Raju et al. used this method to

compare DU finding with phlebography and compared these test to the clinical

severity stage of the patient (Reporting standards in venous disease 1988). They found

duplex findings to directly reflect the clinical severity stage of the limbs. Descending

phlebography failed to identify reflux in 8 limbs in which DU had indicated severe

reflux. Haemodynamic testing in all 8 limbs were consistent with venous disease as

was their clinical findings. This may be explained by the presence of a proximal

competent valve or obstruction within the venous system of these legs which prevents

reflux being shown distally.

Also in nine limbs the opposite occurred, i.e. no reflux on DU but severe reflux on

phlebography. Haemodynamic tests on these patients were normal with only slight

clinical signs of venous disease. This may be explained by the trickling effect of the

heavier contrast medium, or alternatively that phlebography is more sensitive to

58

minimal reflux, however these do not correlate well with the objective functional

assessments in the same way as DU.

Quantification of venous reflux by means of DU has also been shown to correlate well

with fascio-cutaneous changes. Vasdekis et al. (1989) found that the venous reflux

(measured in millilitres per second) was associated with skin changes if reflux was

greater than lOml/s irrespective of site of reflux.

Overall DU appears to be an accurate non invasive technique which compares well

with phlebography and in some studies surpasses venography in the assessment of

patients with venous disease and is now becoming the gold standard for venous

investigations (Mqcqx et al. 1998, Renton etal. 1991 ordered, Singh et al. 1997, Welch

et al. 1996.)

1.7.1.4 Assessment of Incompetent Perforator Veins

With respect to incompetent perforator veins (IPV), ascending phlebography is

thought to be able to localise 81% of IPV (Lea Thomas et al 1972), which can be

increased to 90% by the addition of varicography (Lea Thomas & Bowles 1985).

Clinical examination and continuous wave ultrasound correlate poorly to presence of

IPV as assessed by duplex ultrasound (Schultheiss et al. 1997).

Phillips & Cheng in their paper cast doubt on the ability of DU to detect IPV when

compared against ascending phlebography, as they found that they could only identify

40-60% of IPV. However they had no means of confirming the IPV found on DU and

venography (their gold standard) since exploration of the calf was not performed in

any of these subjects.

A comparison of Colour duplex ultrasound, ascending phlebography and clinical

examination was the basis of a paper by Antoch et al. (2002). They used these

59

modalities to look specifically at IPV within the calf which were then confirmed at

operation by retrograde blood flow in the perforator on calf compression. They found

the sensitivity of DU to be superior to that of ascending phlebography with a

sensitivity of 80%. This figure was improved if combined with clinical examination

but the addition of ascending phlebography yielded no advantage.

Hanrahan et a l (1991) found 35 IPV at operation ( Rob operation) in 19 patients. The

criteria for inclusion was based purely on the diameter (>4 mm) of these vessels at

operation. The same number of IPV were found by ascending venography, which also

used the diameter of the IPV as the basis of inclusion of IPV. Only 26 (74%) of these

IPV were found on DU. Duplex did show a larger number of perforators than

venography, some of which were of a larger diameter than the limit used for surgery

and venography. However these perforators did not exhibit reflux and were hence

assigned as competent. The group concluded that DU may be more accurate in

assessing functional assessment of perforator veins than venography and hence a

higher number of IPV were found on venography which may not have been

incompetent despite their diameter.

The confirmation of DU finding with respect to IPV is perhaps best done at surgery

although no definitions exist with respect to IPV found at surgery. Steigler et al

(1994) found the accuracy of DU in localising IPV to be 95.8% when compared to

operative findings. This was confirmed by Dixon et al. who compared operative

findings with DU findings and found DU to be 100% sensitive and 93% specific with

respect to position of the IPV. Pierik et al. (1995) in their prospective study of 20

consecutive patients found the sensitivity and specificity of DU in predicting the site

of perforating veins on the medial side of the calf to be 79.2% and 100% respectively

for IPV and 82.5% and 100% for competent perforating veins. Meyer et al. (2000)

60

carried out a similar study in 89 legs looked at Cockett’s perforators. They found an

excellent correlation between IPV perforators found by DU (n=76) and ascending

phlebography (n=76) as compared with operative findings of the perforators at

surgery (SEPS, n=83).

Overall it would appear that DU is an accurate and non invasive method of imaging

IPV and correlation with ascending phlebography and surgical findings are good.

PeiToraU)!' \^ in .

Figure 5 Colour DU showing flow within a perforator vein crossing the fascia

61

1.7.2 Investigation of Venous Function

These tests identify correct and incorrect function of the veins. Of special importance

with respect to varicose veins is the function of the venous valves. These techniques

include:

Tourniquet Tests

Continuous Wave Doppler Ultrasound

Descending Venography

Foot Volumetry

Ambulatory Venous Pressure Measurement

Plethysmography

Doppler Colour Flow Imaging

1.7.2.1 Tourniquet Test (Trendelenburg Test)

These are a series of clinical tests aimed at delineating sites of venous incompetence.

The venous system of the leg is emptied by elevation of the leg above the level of the

heart with the patient in supine position. A tourniquet is applied across variable

positions on the lower limb, tight enough to occlude the superficial venous system.

The patient is then asked to stand again and if the veins above the level of the

tourniquet fill, whilst those below it stay collapsed the incompetence must lie above

the level of the tourniquet. However if the veins below the tourniquet fill rapidly there

must be an incompetent communicating vein below it. The tourniquet can be applied

at differing levels in order to more accuracy locate the point of incompetence.

There are several problems with this assessment that makes it fallible and operator

dependent. The position of valves within the venous system are estimated and the

62

tourniquet applied accordingly. Also this examination is not able to detect reflux

below a competent valve since it is dependent of gravity for refilling of the veins.

1.7.2.2 Continuous Wave Doppler Ultrasound

These are the simplest Doppler ultrasound machines used and are usually in hand held

portable sizes. They use two piezoelectric elements which act as transmitter and

receiver. They emit continuous waves which reflect off particles and result in a

change in the frequency of the waves (refer to ultrasound previously). These reflected

sounds are then received and the alteration in the frequencies (Doppler shift) are

converted to audible or visible outputs which allow assessment of movement of

blood. Due to the continuous and simultaneous emission and reflection of the sound

no specific information can be given with regards to depth and position of the veins.

i. 7.2.2.1 Gated or Pulsed Doppler

Pulsed Doppler allows detection of blood flow at a specific defined depth (refer to

ultrasound above). This system has a single piezoelectric crystal which alternatively

acts as source and receiver for the sound waves. By selecting the time interval

between these two processes it is possible to localise signals emitted from specific

depths.

Multi-channels systems now exist which allow simultaneous measurement of

velocities in various neighbouring vessels and using an algorithm calculate a flow

volume quantity.

63

1.7.2.3 Foot Volumetry

This method uses an open water filled plethysmograph. The patient stands, ankle deep

in the temperature controlled water, and exercises (e.g. heel raises). As the blood is

pumped out of the foot, the volume of water drops which can be measured accurately

by the use a calibrated pressure manometer. On resting, the refilling of the veins

results in an increase in the volume. The refilling time is an indication of the severity

of the reflux. Superficial reflux can be distinguished from deep venous reflux by

occlusion of the superficial system by application of a tourniquet.

1.7.2.4 Ambulatory Venous Pressure Measurements (AVP)

As discussed earlier (physiology, venous pump), AVP monitoring is the most accurate

method of assessing calf pump function and assessment of venous insufficiency

(Nicolaides et al 1981, Bjordal 1970). However due to its invasive nature it is not in

common use. Mean ambulatory venous pressure during the relaxation phase of muscle

pump cycle is found to correlate well with the severity of venous disease as well as

being a prognostic indicator of venous ulceration (Nicolaides et al. 1986).

The process itself involves the cannulation of a vein on the dorsum of the patient’s

foot (Browse et al 1999). The needle is connected to a calibrated strain gauge. Once

stable pressure readings are reached, the patient begins a suitable number of

predetermined leg exercises, followed by relaxation whilst holding onto a support

frame. Recordings are taken throughout and displayed in the form of a graph

depicting foot vein pressure against time. The process can then be repeated with the

application of a thigh tourniquet which is moved up and down the leg to determine the

64

contribution of the superficial system and the lowest level of abnormal

communication.

1.7.2.5 Plethysmography

Plethysmography measure changes in the volume of structures, in this case the lower

limb, brought about by the movement of venous blood during calf muscle pump

action. The variety of different types of plethysmography follow this principle the

only difference being the method by which they measure this change in volume. In

this way a quantitative assessment of venous outflow, venous reflux and venous

volume and outflow obstruction can be made.

The earliest instruments used were water-filled plethysmographs which consisted of a

water-filled, watertight container in which the body part is immersed. Changes in calf

dimensions, for example, will displace an equal volume of water which can be

measured in a variety of ways (e.g. the displaced water is collected into a separate

chamber where it compresses air that activates an attached spirometer or a sensitive

pressure transducer, which in turn writes a record on a kymograph). Calibration of

such systems are easily done by adding a known volume of water and due to the

variation of volume with temperature the container is maintained at a constant

temperature.

In principle the process involves raising the lower limb above the atrium to an angle

of approximately 25° in order to empty the veins. A transducer is placed at the calf

and pneumatic cuff inflated at the level of the thigh, so as to occlude the superficial

veins (40-50 mmHg). This results in an increase in calf volume which stabilises

within a few minutes (Venous volume). The cuff is then deflated and the rate of drop

in the calf volume measured by the use of the plethysmograph. Maximum outflow and

65

2s emptying are the commonest indices used to assess outflow obstruction. The rate of

venous emptying is proportional to patency of the deep veins although no distinction

can be made with regards to the position of these occluded veins.

The rate of refilling on standing (Venous refilling time) and variations during exercise

(heel raises, ejection volume, ejection fraction) with and without superficial vein

occlusion by a pneumatic tourniquet, can be performed and give rise to a number of

important indices and can also be used to assess venous reflux and the contribution of

the superficial system.

Other types of Plethysmography are:

1.7.2.5.1 Strain-gauge Plethysmography

The strain gauge plethysmography is essentially a mercury filled rubber tube which is

wrapped around the limb. The changed in the volume in the leg causes changes in the

length of this rubber tube is then reflected by changes in electric resistance of the

strain gauge.

1.7.2.5.2 Air Plethysmography

Air Plethysmography uses a plastic sleeve surrounding the calf, which can be inflated

to low pressures (6-8 mmHg). Changes in calf volume are then detected as a function

of changes in the pressure within the cuff once it has been calibrated.

1.7.2.5.3 Impedance Plethysmography

Impedance plethysmography measures the change in tissue impedance (electrical

resistance) associated with calf volume change. A high frequency low strength current

is passed through two electrodes on a limb. Changes in voltage are recorded via two

other electrodes placed inside the first two. The tissue resistance is related to the

66

volume of blood within the limb and hence these changes during exercise can easily

be measured.

1.7.2.5.4 Photoplethysmography (PPG)

PPG is a non-invasive technique used to detect alteration in blood in the dermal

circulation. In 1938, Hertzman described a method of using reflected light from the

skin circulation and correlating it to skin blood content (Hafner et al. 1999, Vermaart

et al. 1994). Since then PPG has been developed to measure changes in skin

circulation during exercise. PPG contains an infra-red light source and a photoelectric

cell which measures reflected light and converts it into graphical representation which

correlate well with venous refilling times (fig. 7).

This test relates to alteration in the skin blood volumes in response to limb

compression or exercise. These methods have been used in the lower limb where

venous emptying and recovery times have been found to correlate with venous

insufficiency (Abramowitz 1979, Nicolaides and Miles 1987, Rosfors 1990, lafrati et

al. 1994). Norris et al. (1983) used in vivo calibration of PPG and found good

correlations between AVP measured invasively and PPG estimations (fig. 7). They

suggested that this technique if validated by other centres would be a useful non

invasive method to assess CVI. However, with the advent of ultrasound this line of

thought was not pursued in to common clinical use.

Contraction of muscles leads to the compression of veins and return of blood toward

the heart. During the ensuing rest, the blood returns to the lower limb mainly through

the arterial circulation. If the superficial or deep veins are incompetent, blood will

reflux down into the limb and hence the refilling time is shortened. By the use of

tourniquets placed at the ankle and thigh, it is possible to distinguish superficial

venous reflux from deep venous reflux in the sitting position (Nicholaides & Miles

67

1987). This venous refilling time (RT or 90% of refilling time (90%RT)) has been

shown to be reproducible and correlate well with foot vein pressure recovery time

(Abramowitz 1979, Nicholaides & Miles 1987, Norris et al. 1988), although there is

no correlation with mean AVP. It is also important to note that PPG does not give any

measure of venous blood volume but is used to measure venous refilling time

following exercise.

The position of the PPG on the limb is important since refilling times can vary by as

much as 20% depending on the position of the probe (Rosfors 1990). Usually a fixed

point above the medial malleolus is chosen (fig. 6)

Figure 6 PPG probe in position on the medial aspect of the lower calf.

Nicolaides et al. in their study showed that based on PPG refilling times (90% of

Refilling Time (RT) used in this study) patients can be divided into three groups:

Normal valvular function RT = >18s

Superficial venous refiux only RT <18s (increases to more than 18s by obstruction of

the superficial system by means of a tourniquet)

Deep venous refiux RT < 18s (remains <18s with superficial veins occluded with a

tourniquet).

68

However a linear relationship does not exist between PPG refilling time and mean

ambulatory venous pressure (a good indicator of venous insufficiency), and hence

PPG cannot grade the insufficiency but can only detect it.

Photoplethysmography has been used to assess the results of venous surgery and

improvement in the refilling times following surgery have been shown (Pearce et al.

1983).

100

AVP(mmHg)

0

PPG(tracing)

Figure 7 Figure showing the observed changes with simultaneous PPG and ambulatory venous pressure (AVP) monitoring (After Norris et a/. 1983).

69

1.8 VARICOSE VEIN SURGERY

1.8.1 Great Saphenous Vein Surgery

Ligation of the GSV near its termination in to the femoral vein has been the main stay

of surgical treatment of superficial varicose veins. As cited by Browse (1999),

Trendelenburg (1891) was the first to ligate the great saphenous vein in the treatment

of GSV incompetence. Keller (1905) and Mayo (1906) went on to describe stripping

of the GSV and Homans (1916, 1917) published two papers on the treatment and

classification of varicose veins. He was the first to suggest that the GSV and its

tributaries should undergo flush ligation at their junction with the femoral vein.

There is now no longer any doubt that stripping of the great saphenous vein is

significantly superior to ligation alone. It produces a better immediate result and also

a lower long term recurrence rate (Jakobsen 1979, Logfren et al. 1958, Munn et al.

1981). However the stripping of the GSV to the ankle was associated with an

unacceptable high rate of saphenous nerve damage (up to 60%) due to the proximity

of the nerve to the GSV in the lower calf (Cox et al. 1974, Munn et al 1981, Negus

1986). Rivlin went on to suggest that if the stripping is halted at a level just below the

knee, there is less chance of damaging the saphenous nerve and majority of important

perforators are still avulsed. Dissection of 60 cadaveric legs has outlined the anatomy

in the region and suggests that stripping the GSV to below knee level would minimize

the risk of saphenous nerve damage (Holme et al. 1988). Negus using this method

reduced the post-operative neurological complication to 4.2% in his series of 71

patients. Sarin et al. (1992 & 1994) undertook a randomised trial in order to compare

stripping to upper calf against ligation of the GSV alone. They showed there to be no

significant difference in the incidence of saphenous nerve damage in the stripped

70

group (4%), versus the ligation only group (7%). They also showed that post

operatively (within 3 months) the ligation group had a higher incidence of residual

GSV reflux and IPV within the calf. The longer term follow up (median 21 months)

of these subjects with duplex ultrasound and assessment showed a far higher clinical

recurrence in the ligation group as compared to the stripped group. Jones et al. (1996)

went on to confirm these findings in their randomised trial and showed a two third

reduction in the risk of re-operation at 5 years following stripping as opposed to

ligation alone (Dwerryhouse et al 1999).

There are many variations in the surgical technique of High Saphenous Tie and

Stripping and multiple avulsions (HST&S). Below is a brief description of one

technique. An oblique incision is made about I cm or so below the groin crease.

Dissection is deepened within the subcutaneous tissue to outline the GSV. The trunk

of the vein is traced caudally to its junction with the femoral vein after piercing the

cribriform fascia. The junction is clearly dissected out along with all tributaries in the

region outlined previously (anatomy). These are then doubly ligated and divided with

non absorbable sutures. The GSV itself is then ligated and divided flush with the

femoral vein. A small venotomy allows the introduction of a flexible vein stripper

which is fed down within the vein to just below the level of the knee. An incision is

made over the lower end of the stripper and the stripper and vein delivered into the

wound. The vein is divided with the distal end being tied off. The stripper head is

applied to the distal end of the stripper and a ligature tied around the vein containing

the stripper just proximal to the head. The stripper can then be removed by steady

traction, towards the groin.

71

1.8.2 Perforator Vein Surgery and Subfascial Endoscopic

Perforator Surgery (SEPS)

Trendelenburg in 1891, suggested the developed of incompetence of the highest valve

in the great saphenous vein - the concept of descending valvular incompetence. The

failure of these valves means blood can reflux back down the veins, both stretching

the veins (varicosity), and causing inflammation (eczema and ulceration).

In the 1930s it was found that perforator veins lower down the leg, could also fail, and

allow blood to leak out of the deep veins, causing excess blood in the superficial

veins. Linton (1938) began to realise the importance of interruption of the IPV in the

treatment of varicose ulcers. He began open ligation of perforator veins in the belief

that they were responsible for venous ulceration and hence their ligation would heal

chronic venous ulcers. In 1953 Linton began to use a single medial incision, rather

than the three longitudinal incisions he initially used. Through this he was able to

access most IPV. Although successful in healing most ulcers (Cockett 1955, Fields &

Van Boxel 1971, Haeger 1966) this technique was plagued by delayed wound healing,

flap necrosis and wound infections in up to 58% of the cases (Stuart et al. 1997, Puts

& Gruwez 1993). Puts et al. confirmed the complications with skin necrosis. However

they managed to reduce the rate of skin necrosis by 6.7 times in non ulcerated patients

and 4.2 times in ulcerated patients by the use of a combination of low molecular

weight heparin and piracetam. Cockett (1955) advised extrafascial ligation of the IPV

(Subcutaneous) as he felt that the integrity of the deep fascia around the distal soleus

muscle was important in calf pump function. Dodd (1964) described a postero-medial

subfascial approach in order to avoid dissection of unhealthy tissue. The Rob

Procedure described by Healy (1979) used a long “stocking seem incision” to perform

posterior subfascial ligation and Depalma (1974) used multiple parallel incisions in

72

the Danger’s line along the medial aspect of the calf. Unfortunately these procedures

were found to have very high morbidity (Cockett 1955, Fields & Van Boxel 1971,

Haeger 1966, Puts & Gruwez 1993, Stuart et al. 1997) and have since been

abandoned as routine procedure for perforator ligation. Pierik et al. (1997) in their

randomised trial compared SEPS to modified Linton procedure and had to halt the

trial at 15m follow-up. An unplanned interim analysis carried out due to perceived

complication rate in the open technique revealed an unacceptable high rate of wound

complication in the modified Linton group (53%). They however went on to follow-

up these patients and found that in both groups the venous ulcer healing rate was

good. The recurrence rate in the modified Linton group was 22% and in the SEPS

group 12%. They concluded the long term follow up results of SEPS to be as good as

the modified Linton procedure (Sybrandy 2001).

Subfascial shearing, a technique described by Albanese (1965, 1969), was probably

the forerunner to SEPS. An incision is made on the medial side of the upper thigh and

the subfascial space found. Shearers (blunt instruments invented for the procedure),

were then introduced into this space and pushed down towards the medial malleolus.

By manipulating the instrument in this space all the communicating veins were thus

divided, which often resulted in considerable bleeding from the incision.

Subfascial Endoscopic Perforating Surgery was described by Hauer in 1985 (as sited

by Browse 1999) and introduced to the UK in the early 1990s. Other European

surgeons described their experience and improvements on the technique (Couto &

Bapista 1991, Jugenheimer & Junginger 1992, Pierk 1995, Wittens 1995).

Conrad et al. (1994) in Australia, simultaneously with Golviczki et al. (1996)

described carbon dioxide insufflation in the subfascial compartment in order to

improve subfascial visibility and to expand the working space. After exsanguination

73

of the limb using an Esmarch bandage, a pneumatic tourniquet is inflated to a pressure

of 300 mm Hg. At approximately 8 cm distal to the tibial tuberosity and 3cm from the

tibial edge, a 15mm incision is made and the first 10mm port inserted into the

subfascial space. Carbon dioxide insufflation is then commenced to a compartment

pressure of 30 mm Hg. A laparoscope is then inserted in the first port and a second

10mm port is inserted under direct vision. After the IPV are identified two 10mm

clips are placed across the vein and which is then divided by the use of endoscopic

scissors (fig. 8,9,10).

The use of SEPS in primary non ulcerated varicose veins in the UK is undertaken

selectively (Whiteley 1998) and to date no published randomised trials have assessed

their use in treatment of primary and recurrent non ulcerated varicose veins. Published

experiences with SEPS show acceptable results (Conrad 1994, Gloviczki et al 1996,

1997, 1998, Hauer et al 1988, Pierik et al. 1995, 1997, Rhodes 1998, Stuart et al.

1997,). In one retrospective study (Jugenheimer and Juginger 1992) post-operative

wound healing delay was seen in 2.9%, 2 (1.9%) patients complained of dysaesthesia

in the distribution of the sural nerve and 9.7% in the region supplied by the saphenous

nerve (they also had stripping of the GSV). Other complications included

subcutaneous haematoma in 5.8%. New or persisting IPV were found in 2 patients

after a 27 month follow-up.

At our centre, as will be described in the methods, we use a modified scope and no

carbon dioxide insufflation. The entire medial aspect of the calf can be visualised and

accessed by the use of a single specialised 16mm SEPS scope. The IPV are clipped

but not divided since division of such veins may lead to an increased incidence of

haematoma which may be mistaken for deep venous thrombosis Kianifard {et al.

2002).

74

Figure 8 IPV as first seen during the operation

Figure 9 IPV dissected out

Figure 10 SEPS clips across an IPV which is divided in this case.

75

1.8.3 Perforator Vein Surgery in Primary Non Ulcerated Varicose

Veins

The place of SEPS in the management of primary non ulcerated varicose veins has

not been established (Browse etal 1999). The management of patients with IPV in the

presence of symptomatic non ulcerated legs with and without CSV reflux is unclear.

Despite an extensive literature search no meaningful studies were found to answer this

question.

In almost all studies on the subject the pathological IPV were most often seen on the

medial side of the calf with the lateral aspects almost invariably spared. It is also clear

that the number of IPV increases with increasing grades of chronic venous disease

(Delis et al. 1998, Jiang et al. 1999, Labropoulos et al 1995,1999, Nelzen 2000).

Some studies have also examined the size of the perforator in order to assess a

correlation with significant reflux. Labropoulos et al (1999) found that the size of

both incompetent and competent perforators increased with severity of the disease

with the largest being found in the middle and lower calf. In this study the best cut off

diameter for prediction of incompetence with in the perforator was >3.9mm in

diameter. However this only gave a sensitivity of 73% which was in line with other

studies. Phillips and Cheng (1996) performed US scans on legs of 50 healthy and 90

symptomatic patients and compared the perforator veins which they found. In the

control group they found perforator veins in 36% of the subjects, 83% of which were

< 3mm, non of which exhibited reflux. Of the remaining 17% all were between 3 and

4mm and again no reflux was seen within these perforators. In the symptomatic group

78% of the patients had perforator veins, with 18% being < 3mm and 25% of which

exhibited reflux. Of the remaining 82%, all were >3mm and 54% of which exhibited

reflux. They recommended that due to missed perforators (lack of sufficient

76

retrograde flow of blood) on DU all perforators >4mm should be regarded as

incompetent regardless of demonstration of reflux. Yamamoto et al. (2002) compared

pre-operative perforator vein diameters as assessed by DU with intra-operative

diagnosis of IPV as assessed by bleed-back test. They found that IPV had a larger

diameter than competent perforator veins and that perforator veins with a diameter of

>3mm were 80.4% predictive of incompetence and recommended surgery for all

perforators >3mm. Similar results were found by Sandri et al. (1999) who showed

that 90% of IPV >3.5mm were incompetent after assessing 500 perforators in 78

patients.

Labropoulos et al. (1999) compared the duplex finding of healthy volunteers to those

of patients with chronic venous disease. In the 30 normal limbs which they examined

they found 106 perforator veins all of which were competent. In those with venous

disease 581 perforator veins were found in 103 limbs, 28% of which were

incompetent. They also found 74% of IPV were associated with superficial vein

reflux alone and the combination of superficial and perforator vein surgery has been

shown to have a haemodynamic benefit to these patients (Bradbury et al. 1993,

Padberg et al. 1996, Rhodes et al. 1998). Padberg et al. and Sales et al. (1996)

showed that segmental deep venous reflux was reversed in patients following such

procedure. However following stripping of the CSV alone Walsh et al. (1994) found

segmental deep venous reflux to also be abolished.

The isolated pathological haemodynamic contribution of IPV to chronic venous

disease has been a questionable one. Some authors have cast doubt on the significance

of this contribution (Bjord 1988, Bumand et al. 1977, Stacey et al. 1988), whereas

others have found IPV to be important in the pathogenesis of chronic venous disease

77

(Cockett & Elgan Jones 1953, Zukowski et al. 1991, Pierik et al. 1995, Gloviczki et

al. 1997b).

Zukowski et «/. (1991) measured ambulatory venous pressures in patients with patent

deep veins. They studied 180 patients with superficial venous disease only. They

showed a significant contribution by the IPV to the abnormal haemodynamics (as

measured by the time required for post exercise pressures to return to 90% of normal),

of primary varicose veins especially in the presence of segmental deep venous reflux.

Thirty five percent of these perforators were found to be of major haemodynamic

significance and 35% of moderate haemodynamic significance.

In order to study the isolated haemodynamic contribution of deep, superficial and

perforating veins McMullin et al. performed ascending phlebography, duplex scans

and A VP measurements in 90 patients. Seventeen of these patients were found to have

no deep or superficial abnormality on duplex scanning and phlebography showed all

of these limbs to have an average of 2 IPV. This group of patients were symptomatic

and were found to have a Venous Sufficiency Indexes (VSI, a measure of refilling

time and drop in pressure on exercising) which was significantly lower than those

with no venous abnormality with in their limbs. They concluded that the

haemodynamic abnormalities and symptoms were due to the IPV. They also found

that the VSI of those patients with deep venous insufficiency to be significantly lower

than those with IPV only. From this they concluded that IPV did not develop as a

result of Deep venous insufficiency (DVI) and may occur as a primary abnormality.

Goldman et al. (1994) in their review of varicose veins state that IPV can exist

independently and cause an increase in deep venous pressure.

The single randomised trial looking at haemodynamic contribution of IPV was

performed by Fitridge et al. (1999). They randomised 38 uncomplicated limbs to

78

superficial surgery with and without flush ligation of the IPV. The patients were

assessed using air plethysmography pre-operatively and 3 months post-operatively.

They found no differences between the two groups at 3 months and concluded that

further follow up is required to assess the impact of perforator surgery in the long

term.

A much quoted study by Campbell and West (1995) found that 80% of IPV were

closed at 6 weeks following HST&S. This was a retrospective audit study to assess

operative treatment for varicose veins and included patients with all manner of

superficial reflux disease. At their follow up DU assessment (between 2 and 6 weeks

post operatively) they found that 80% of the previously IPV had become competent or

showed no flow, despite undergoing no direct intervention. However there was no

follow up data beyond six weeks to assess the patency of these IPV in the longer term.

There is evidence of IPV being directly responsible for varicose veins. Jutley et al.

(2001) reviewed their DU results on 223 limbs referred for symptomatic

uncomplicated primary varicose veins. They found 30% of the patients to have a

competent SFJ. In 29% of these, varicosities could be explained by IPV in the thigh

(47%) and calf (53%). Seidel et al. (2004) found IPV to be responsible for 17% of

primary varicose veins in 735 patients they scanned with an intact saphenous trunk.

Their selected group of patients attended their private clinical with mostly cosmetic

complaints. In a study of 500 consecutive patients awaiting surgery 56.4% of them

were found to have IPV on DU. (Sandri et al. 1999).

Certainly the association of IPV with recurrent varicose veins has been established.

Duplex based studies on varicose veins, carried out at our centre have shown an

increase incidence of IPV in recurrent varicose veins than in primary varicose veins

79

(63% vs. 44%, Rutherford et al 2001). Jiang et al. (1999) in their series of 172

patients with recurrence also found 2/3 to have an IPV.

Labropoulus et al. (1996) reviewed their duplex results of 134 limbs with recurrent

varicose veins. They found IPV in the thigh and calf to be directly responsible for

recurrence in up to 50% of their series. One third of all patients who had had previous

stripping of the GSV had IPV in the calf. Interestingly the same proportion of patients

were found to have IPV following ligation of the SFJ. This negates the notion put

forward by Campbell & West that 80% of IPV become competent following HST&S,

and stripping does not appear to protect against development of IPV.

Similar high rates of recurrence have been quoted by Thibault & Lewis (1992) as the

cause for recurrent varicose veins (61.5% recurrent limbs with IPV). Tong & Royal

(1995) in their duplex study on 244 recurrent limbs found 25.8% of them to have IPV

involved in the recurrence and England (1996) in a similar study found IPV present in

69.2% of his series of 267 recurrent limbs. Other studies quote a much lower rates of

recurrence as a result of IPV (Corbett et al. 1984, Dwerryhouse et al. 1999, Gamer et

al. 2003, Redwood & Lamber 1994).

Over all the majority of the studies carried out do not answer the question of treatment

of IPV in primary non ulcerated varicose veins. Certainly there appears to be

improvement in the haemodynamics of the limb when perforator surgery is combined

with superficial reflux ablation, although this is questioned by Fitridge et al (1999).

Other studies have shown a significant haemodynamic contribution by the IPV to

venous hypertension. The majority of these studies look at a mixed group of patients

which include those with SSV, deep vein perforator vein reflux as well as presence of

ulceration and the contribution of each system to the overall picture is impossible to

assess. The constant finding of increased number of IPV in primary VV as compared

80

to normal legs, and the increase in number of IPV in legs with recurrent varicose

veins as compared to legs with primary varicose veins, along with the correlation of

number of IPV with grade of venous deficiency does implicate these perforators in the

pathogenesis of varicose veins.

1.9 RECURRENT VARICOSE VEINS

Recurrence after varicose vein surgery for primary or recurrent varicose veins, is

unfortunately common. The reported incidence of recurrence varies widely depending

on means of assessment and diagnosis, type of procedure undertaken and time of

assessment after the primary procedure, case mix and clinical classification. However

the incidence is thought to be in the region of 7 to 80% at 3-10 years (Royle 1986,

Jones et al. 1996, Darke 1992, Jiang et al. 1999, Campbell et al. 2003, Rivlin 1975).

The aetiology of such recurrences is probably multifactorial and the numerous studies

detailing recurrences use differing definitions and methods of investigating (Perrin et

al. 2000). The common reasons for these recurrences are:

1.9.1 Inadequate or Inappropriate Surgery

1.9.1.1 Failure of Sapheno-Femoral Ligation Or Missed Branches at the Junction

Rivlin (1966, 1975) found that 72% of his series operated on for recurrent varicose

vein had inadequate surgery at their primary procedure. This was also noted by other

investigators and is thought to be one of the commonest reasons for recurrence

(Bradbury et al. 1993, Englund R 1996, Glass 1989, Lofgren & Lofrgen 1971, Haeger

1961, Negus 1993, Stonebridge et al. 1995, Gamer et al. 2003). The recurrences were

shown in one paper to be more commonly seen in patients operated on by junior

81

trainees (Lees et al. 1997), hence emphasising the need for correct training and

supervision in order to improve the recurrence rates. Turton et al. (1997) found this

to be remediable by proper supervision of juniors by consultant surgeons and

sufficient attention to ligation of the junction and the tributaries.

Defining the anatomy of sites of recurrence is imperative in planning surgery. Duplex

ultrasonography outweighs all other modes of investigation for assessing recurrent

varicose veins providing a non invasive technique which accurately provides both

anatomical and functional information (Benabou et al. 1998, Englund 1996, Jiang etal

1999, Perrin et al. 2000, Tong & Royle 1995). There have been many publications on

this topic. Redwood & Lambert (1994) found 58% of their 99 patients with recurrent

varicose veins to have incompetence at the SFJ but they do not distinguish between

neo-vascularisation and an intact system. Jiang et al. in their paper scanned a series of

264 limbs all of which had previously undergone sapheno-femoral ligation or

stripping. Overall 65.2% of this group had a recurrence at the SFJ. These included:

-Pristine SFJ indistinguishable from primary varicose veins with the GSV

intact ( 17.4%)

-Narrow SFJ - refiuxing into an intact GSV (15.2%),

- refiuxing into local varicosities (11.7%),

- refiuxing into an intact GSV and groin tributaries (6.4%)

-A cluster of small veins communicating with an intact GSV or varicosities

(11.4%)

-No reflux at the SFJ, but from epigastric or perineal veins (5.7%).

82

Out of 143 patients who had their GSV stripped, 43.3% (62/143) had a GSV or a

similar vein present in that position. This figure was increase to 73.6% in those who

were not stripped. Labropoulos et al. (1996), in their retrospective study found 35% of

their series had SFJ incompetence. Englund in his series of 267 recurrent limbs found

44.6% of them to have an intact SFJ and GSV.

1.9.1.2 Aberrant Anatomy

At surgery anatomical variations at the SFJ can lead to incorrect surgery performed as

a result of mistaking the SFJ or the GSV. Browse et al (1999) say that the large

medial and lateral superficial thigh veins can be mistaken for the GSV and can

presumably be stripped instead of the GSV. In their experience duplication of the

GSV occurred in 5% of their patients which again may be a source of erroneous

surgery. Also they suggest that the numerous anatomical variations of SFJ exist (e.g.

direct entry of one or more tributaries into the femoral vein) which may cause

mistakes at operation if the SFJ in not properly exposed.

Jutley et al. (2001) in their retrospective study of uncomplicated symptomatic primary

varicose veins found an anatomical variation in 24% (53 limbs) of their patients

which would not have been detected clinically or by hand held Doppler. Fifty nine

percent of these comprised of splitting of the GSV into two or more within the thigh

with at least one of these branches eliciting reflux. In 19% the origin of the GSV was

found to be bifid.

Corrales et al. (2002) suggest that the incidence of duplication of the GSV to be far

higher than this. They reviewed 109 saphenograms undertaken in preparation for

peripheral bypass surgery. In almost fifty percent of these they found evidence of

duplication of the GSV, most being in the form of a closed loop in the thigh. Thomas

83

(1979) in his cadavaric study found true duplication of the GSV (i.e. splitting within

the superficial fascia proximally and rejoining into one channel) to be uncommon

(8%). This area of error can by enlarge be overcome by pre-operative DU of all

patients.

1.9.1.3 Incompetent Thigh or Calf Perforators

Work performed at our unit (Rutherford et al. 2001) has shown 44% of patients with

primary varicose veins have incompetent perforator veins, (0.55 and 0.14 per leg

associated with great saphenous and small saphenous veins respectively), where as

63% of patients with recurrent varicose veins have incompetent perforating veins,

(0.84 and 0.37 per leg associated with great saphenous and small saphenous veins

respectively). The incidence of IPV in recurrent veins are similar to findings from

other studies out lined previously (Englund 1996, Jiang et al. 1999, Labropoulus et al.

1996, Thibault & Lewis 1992, Tong & Royal 1995). Thus there is a significant

association between both the presence of and the number of IPV, and recurrence of

varicose veins.

Although 80% of incompetent perforating veins associated with great saphenous

reflux are thought to become competent in the short term surgery (follow up of 6

weeks), 20% do not (Campbell & West 1995) and the long term position of these

perforator veins is unknown. This coupled with the high number of recurrences

following surgery and the number of incompetent perforators associated with varicose

veins, suggests that our understanding of pathogenesis of varicose veins is incomplete

and may implicate a more important role for incompetent perforating veins. Hence

SEPS used in conjunction with traditional surgery should reduce the rate of recurrence

in primary and recurrent varicose veins in patients with proven perforator vein

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incompetence. However despite a thorough search of the literature no meaningful

studies were found to answer this question.

1.9.2 Regeneration I Neo-vascularization

Glass (1987a) did much to put the idea of neo-vascularisation on the map of recurrent

varicose veins. He cites work by Langenbeck, and Perthes in the late 19th century as

the first to note regeneration of new veins following ligation of the SFJ. Later

Homan’s went on to state that recurrent veins were either as a result of opening of

collateral vessels in the region or new vessels with in the scar tissue (neo-

vascularisation). Thereafter the theory of inadequate surgery and missed collaterals

became more popular and took over as the explanation for such recurrences (Lofgren

& Lofrgen 1971, Rivlin (1966, 1975), Negus 1993, Lees et al. 1997). Glass performed

ligation of the SFJ under local anaesthetics aimed at healing venous ulcers. These

patients then underwent HST & S and multiple avulsions once the ulcer had healed. In

10 of these patients, he performed insitu phlebography examination and radiographic

and histological examination of the excised vessels. He showed a fine anastamotic

network which had developed within the scar tissue between the proximal and distal

ends of the ligated veins. Histological studies revealed this to be a step by step

progression of development. At 2 weeks, an organised blood clot occupied the gap

between the two ends of the veins with blood vessels extending into the area from

surrounding tissues. At six weeks the thrombus was adherent to the vessel wall with

evidence of recanalisation with numerous small abnormal vessels extending in

parallel arrangement into the connective tissue. At 12 weeks muscular walls were

observed in the wall of these veins, and at 40 weeks the thrombus had resolved

completely with large thin walled vessels joining the two ends of the veins. By 64

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weeks the walls of the vessels were thicker and contained abundant muscle and elastic

tissue resembling that of mature recurrent veins. These findings were equivalent to his

findings in rat models which had undergone surgical interruption of their iliac or

femoral veins (Glass 1987b). He concluded that a large pressure difference in a vein

proximal and distal to the site of transection appeared to be necessary for the

restoration of its continuity. In 1989 Glass published his data and concluded that

recurrence can be reduced by closure of the cribriform fascia and or covering of the

SFJ with synthetic mesh.

Since then many studies have shown neovascularisation to be the principle cause of

recurrence following diligent surgery ( Darke 1992, Van Rij etal 2003, Jones et al

1996), . Jones et al. (1996) found neovascularisation (serpentine tributaries arising

from the ligated SFJ) to be the principle cause of recurrence in their study. Fifty two

percent of their patients followed up by duplex ultrasound as part of randomised trial

(stripping versus ligation of the GSV) were found to have neovascularisation at the

SFJ (24/53 in stripped, 35/60 ligated) 2 years post-operatively. All patients with

tributaries >3 mm were found to have clinical recurrence as did 55% of those with

tributaries <3mm. Nyamekye et al. (1998) re-explored 28 legs with recurrence at the

SFJ. They took block dissections of the region which were histologically examined

for neovascularisation. Twenty seven of the 28 groins showed evidence of

neovascularisation and it was found to be the commonest cause of recurrence. Of

particular note was the complete lack of mural nerves (stained with SI00) in these

immature veins. De Maeseneer et al. (1997) prospectively followed up a consecutive

group of new patients following surgery. They performed duplex scans at 2 months

and 12 months post-operatively. All of these patients had pre-operative duplex scans

and 122 patients underwent HST&S. At the 2 month follow-up scan 2% of the total

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had a small communication (<4mm) at the sapheno-femoral junction. At the 12 month

scan out of the 122 patients who had undergone stripping 12 had mild neo­

vascularisation (<4mm) and 2 had moderate neovascularisation at the SFJ (>4mm). It

would seem that with the advent of correct surgery, neovascularisation appears to be

the commonest cause of recurrence. This finding was confirmed by Van Rij et al.

(2004). They performed HST&S on 42 patients (49 SFJ) with recurrent varicose

veins. All but three of these patients (94%) showed neo-vascularisation at the SFJ.

Histological specimens of these junctions taken during procedure, showed all to have

abnormal architecture inconsistent with that of a normal SFJ, i.e. neo-vascularisation.

They further suggest that neo-vascularisation may be as a result of angiogenic stimuli

from surgery, which is not a general feature of venous surgery since neo­

vascularisation is not observed at sites of GSV harvesting for bypass surgery. This

implies that the underlying venous abnormality may persist in these recurrent patients.

They suggest that the endovascular procedures for varicose veins may in this way

reduce the rates of recurrence since they do not induce a vigorous angiogenic

response. This has been shown by our comparative study looking at

neovascularisation following radio-frequency ablation and HST&S (Kianifard et al.

2005 in press).

1.9.3 De novo Reflux

As outlined by the Framingham study the two year incidence of varicose veins was

39/1000 in males and 52/1000 in females in a longitudinal study. This implies that

patients may develop varicose veins following surgery, in the remaining previously

competent veins of the leg due to thus far undetermined factors.

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1.10 QUALITY OF LIFE ASSESSMENT

The assessment of treatment outcome from the perspective of the patient has gained

more importance in the modem era of medicine. This enables measurement of the

effects of treatment on the quality of life of the patients. In order to use instruments to

evaluate such factors, the tests must be reliable, valid, responsive and practical.

Attempts to produce such instruments have been in the form of questionnaires which

have undergone large scale use and modification to become important tools in

assessment of treatments and quality of life. Broadly these questionnaires can be

divided into two groups. The first is the generic form of the questionnaires aimed at

evaluation of the quality of life and health related maters. These questionnaires, such

as the short form 36 (SF 36) are broad tests which are non specific and aim to

evaluate the overall health status. The second type of questionnaire is a specific

instrument which focuses on a particular disease (e.g. Aberdeen questionnaire (AQ)

for varicose veins). Many investigators in this field advise the concurrent use of these

questionnaires (Garratt et al 1993a, Patrie & Dayo 1989, Ware et al. 2000).

In order for a questionnaire and the scoring system to be useful, it has to be reliable

and valid. Reliability is the extent to which measures give consistent or accurate

results. This entails an estimation of how much of the variation in score is due to the

truth as apposed to chance random errors. The tests carried out need to examine the

consistency of the questionnaire by evaluating and comparing the different measures

designed to measure the same variable (internal consistency).

The stability of the questionnaire i.e. the correlation of the scores on re-testing the

subjects can also be tested to assess reliability. An important factor in test re-test

procedures is that the time gap between tests must be taken into account with respect

to the condition, since physical changes noted by the questionnaire may be real ones.

An alternative method of assessment would be to compare findings with an alternate

method of measuring the same criteria and comparing the results.

The split-half correlation is a more commonly used method to assess the reliability

and internal consistency. This compares 2 halves of a test designed to assess the same

characteristic i.e. scores from questions in the same questionnaire which measure the

same characteristics. Both halves of the results should produce similar results as

expressed by coefficient a, the average of the possible split-half reliabilities adjusted

for the original number of items. Alpha values of > 0.7 are thought to correspond to

good internal consistency (Cronbach 1951, Jenkins et al. 1993).

Validity, the extent to which the results relate directly to the characteristics being

evaluated (i.e. testing the underlying theory), can be divided into:

Content validation - Once the internal structure of the questionnaire is

established, theoretical relationships between the various domains and external

criteria are outlined based on theoretical knowledge of the criteria being measured, or

by alternate established tests. One example would be to test the difference in two

groups known to differ in some way (e.g. patients with complicated medical histories

should score lower than those with no medical history).

Convergent validity - is supported when different methods of measuring the

same criteria produce similar result (e.g. physical function and mobility).

Discriminatory validity - tests whether one aspect of the questionnaire can be

differentiated from another, (e.g. physical function and measure of loneliness)

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Criterion validity - shows that the test scores are systematically related to

some outcome criteria and requires a known external factor against which the scores

can be assessed.

1.10.1 Short Form 36 (SF36)

“Psychometrics” is the use of standardised scales or tests to measure the attributes of

an object. This theory has been used to interpret patient ratings into scales and

numbers to measure health. One of the most extensive applications of psychometric

analysis took place during the Health Insurance Experiment (HIE), which attempted

to devise a scale to measure a wide spectrum of functional status in a broad age group.

These techniques involved the construction of scales based upon questions asked in an

attempt to analyse the health status of subjects. The HIE found such tests to be valid

and reliable, but their application, in the form of long self administered surveys were

cumbersome due to the number of questions asked. Also their application in disease

was not as yet established. Subsequently several short form scales based on the

original questionnaires were devised and used successfully. The Medical Outcome

Study (MGS) was a further development from HIE, where 40 physical and mental

health scores were tested in the form of self administered questionnaire to assess the

impact of components of American health service on the outcome of care. The SF36

was developed from eight of the most important health concepts included in the MGS

which best described the overall health status of the individual (Ware et al. 2002).

These eight attributes are measured using multi-item scales containing 2 to 10 items

each.

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These are:

Physical function

Role-physical

Bodily pain

General health

Vitality

Social functioning

Role-emotional

Mental health

Reported health transition

The attributes in the questionnaire are each scored and are summed up to give a total

out of 100 with higher scores representing better states of health (Ware et al. 2002).

This scoring system has been used in a number of studies and has been found to

correlate well with the health of the individuals (Brazier et al 1992, Garrett et al.

1993a, Jenkinson et al. 1993). Brazier et al. (1992) conducted a survey in 1980 British

patients using the SF36 questionnaire (anglicised version) and found a Cronbach’s a

coefficient of > 0.85 and a reliability coefficient of 0.75 for all dimensions of the

questionnaire except for social function. Very similar coefficients were found by

Jenkins in his survey of 13042 of the population in the U.K.

Ruta et al. (1994) showed the SF 36 to be reliable as tested on two groups of patients.

Group 1 included 1787 patients which were divided into 4 groups, back pain,

menorrhagia, varicose veins and suspected peptic ulcer. These were sub-divided into

patients referred to hospital and those treated by the General Practitioner. Group 2

consisted of 573 patients attending the gastroenterology clinic. They tested the

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internal consistency of the device by using Cronbach alpha which was > 0.8 for all

sections of the SF36 in both groups. The test re-test consistency was expressed as

correlation coefficients which were 0.66 - 0.93 in group 1 and 0.79 - 0.94 in group 2.

A review of the studies (n=14) undertaken in estimating the reliability of each scale of

the SF36 questionnaire found a reliability coefficient of 0.8 or more in each scale

(Ware et al. 2000).

Validity is the extent to which the score pertains to what it is supposed to mean, i.e. if

it represents the intended interpretation. Content validity requires a pre-existing

standard measure or sound theoretical basis along which a comparison of results

found can be made. Construct validation examines both the test and the underlying

theory by creating a domain of variables with in the questionnaire and establishing an

internal structure of the observed variables and verifying the theoretical relationships

between the scale scores and observed criteria. An example of this would be patients

with known mild conditions should score higher (i.e. better) than patients with

moderate to severe conditions. The foundations of construct validation are

convergence and discriminatory validity. Convergent validity is fulfilled when

different methods of measuring the same object provide similar results.

Discriminatory validity determines whether one underlying construct can be

differentiated from another, (e.g. one would not expect a measure of loneliness to

correlate with physical function).

Criterion validity shows that test scores can systematically be shown to represent one

or more outcome criteria. In order for this technique to be used the evaluator must

know what the anticipated result should be by means of comparison with external

validated evidence. These correlations may be negative (e.g. age and physical health)

or positively (e.g. physical and mental health scores against general health).

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Garratt et a l (1993a) was one of the first to validate the SF36 form in the UK. He

performed a postal survey on 1787 patients which were broadly divided into four

groups (with back pain, varicose veins, menorrhagia and suspected peptic ulcer

disease). The source of these patients were identified from referrals from General

Practitioners or those being treated by the practitioners without a referral to a

specialist. The response rate was over 75%, reliability was found to be high

(Cronbach s a exceeding 0.8) and correlation between items and remainder of their

own scale was also higher than those with other scales, providing further evidence of

internal consistency. In this study two methods of validation were used. The first was

the psychometric test which showed a ‘eigen value’ (statistical measure to explain the

variations between patients are not by chance), above 1.1 for all sections in the

questionnaire. Construct validity was confirmed by assuming patient referred by the

General Practitioners were likely to score lower than those which were not referred,

and the greatest difference in the scores from the general population were expected to

be the back pain group and the lowest the varicose veins group. These were by

enlarge confirmed and correlated well. Although the varicose veins group showed the

smallest difference from the normal population, the study showed that such patients

can be distinguished from the general population. Jenkins et a l 1993 also validated

the SF36 in his large survey of population picked at random fi-om general practices.

He found patients who had reported a long illness or had attended their General

Practitioners, consistently and significantly scored lower than the rest. He also found

good correlation between the items and the variable to which they contribute. Brazier

et a l in their study compared the SF36 to the Nottingham Health Profile and were

able to find the weak points associated with the Nottingham Health Profile. In this

study 1980 randomly selected patients from General practices were surveyed. They

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found the SF36 to be reliable and valid as their distribution of the scores corresponded

with what might have been expected, (e.g. higher age and physical function, lower

social class and health, consultation with GP in last 2 weeks and perceived health).

By its extensive use in clinical settings SF36 has emerged as a reliable and valid tool

for measuring outcome of health.

1.10.2 Aberdeen Questionnaire

Having assessed the use of SF36 in patients with varicose veins, Garrett et al. went on

to develop a specific questionnaire for varicose veins based on questions deemed

relevant by 2 consultant vascular surgeons (Garrat et al. 1993b). The surgeons went

on to score possible responses to each question allocating zero for normal and a score

to all other categories in proportion to their perceived contribution to severity. The

two scores were then summed, averaged and rescaled to produce total scores ranging

from 0 to 100 (normal to the worst, i.e. the opposite to that of SF36). This

questionnaire along with the SF36 was distributed to 373 patients with varicose veins

(287 referred by General Practitioner, and 86 who had just attended the practitioner),

and 900 random sample of the population. The questionnaire was validated against

the SF36 scores for each patient. Two out of the fifteen questions they started with

were discarded since they were found not to correlate with the 4 specific and

important clinical factors confirmed by the vascular surgeons. This achieved a

Cronbach’s alpha value of 0.72. All scales of the SF36 were found to correlate well

with the varicose vein score apart from mental health and general health perception

(correlation of 0.31 and 0.25 respectively). Garratt et al. (1996) go on to further test

the use of this tool with respect to the reliability, validity and responsiveness to

changes in health by following up these groups with a repeat survey at twelve months.

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Further validation for the specific instrument was shown by the correlation of the

individual items with in the instrument and the SF36 score. Both instruments were

validated by good correlation with both the practitioners rating of the disease and the

known complications associated with the condition. Only a few of these results were

however statistically significant but the majority were in the direction hypothesised by

the researchers. Patients surveyed at 12 months were divided into those who had been

admitted to hospital in that period and those who had not. Their score in both

questionnaires were compared to the health transition question in the SF36

(‘compared to one year ago, how would you rate your health now?’), and the strong

relationship between these factors further validates both questionnaires. The largest

improvement over the 12 months was found in the group admitted to hospital for

surgery. The health profile at one year in this group was better than the mean found in

the general population. The profile for the group not admitted to hospital improved

very little. The sensitivity of these instruments for changes in health was also

investigated by means of Standardised Response Mean (SRM, the mean change in

score for a scale divided by the standard deviation of the change). As would be

expected in patients with varicose veins, the specific questionnaire was far more

responsive than the SF36. The largest SRMs were found in patients admitted to

hospital.

This specific questionnaire went on to be called the Aberdeen questionnaire (AQ) and

in conjunction with SF36 further work in its assessment of varicose veins before and

after surgery has been carried out. In a prospective study, 137 patients filled out the

AQ, SF36 and patients symptoms and concern tick box form before and 6 weeks after

surgery for varicose veins (Smith et a l 1999). The AQ was found to be reliable

(Cronbach’s alpha > 0.7). Highly significant correlations were found with the patient

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symptoms and concerns form which further validates the AQ in this setting. Overall

there appears to be sufficient evidence in support of AQ as a specific tool in the

assessment of patients with varicose veins.

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2 CHAPTER 2

2.1 METHODS AND MATERIALS

2.1.1 Proposal and Ethical Approval

The lack of scientific evidence in support of, and against the use of subfascial

perforator vein surgery (SEPS) in primary varicose vein, has led us to the construction

of this randomised control trial to investigate the use of SEPS in this area. The fate of

these Incompetent Perforator Vein (IPV) following surgery for primary varicose veins

is unknown. The prime objective of this study was to assess the effects of varicose

vein surgery on these IPV as assessed by DU (primary outcome).

In order to assess the effects of SEPS on the fate of IPV we devised a randomised

clinical trial with one arm of the study undergoing SEPS as part of their surgery. Our

hypothesis was that the addition of SEPS to HST&S, would reduce the number of IPV

seen to be refiuxing at one year. Also as secondary outcome measures

photoplethysmography, quality of life and visual analogue scores, analgesic use,

operative times, and walking speeds were assessed over a 12 month period following

surgery.

A proposal for the trial was drawn up along with standard pro forma (appendix 1) in

relation to the different aspect of the trial. Patient information sheets (appendix 1) and

consent forms (appendix 1) were also constructed and the trial was approved by the

Local Ethical Committee (South West Surrey Local Research Ethics Committee).

97

2.1.2 Sample Size

From Campbell (1995), 20% of patients will have incompetent perforators after high

tie and strip versus approximately 5% (P2) to allow for missed perforator ligation at

SEPS. However clinical experience shows that the number of refiuxing veins is likely

to increase and an estimation of 40% (PI) at one year seems reasonable. Assuming

that there will be a difference between these groups that will be apparent on duplex

ultrasonography (DU):

The expected proportions are 0.40 (PI) and 0.05 (P2).

P1-P2Hence the standard difference = voa-w)Where = (PI- P2) / 2

Therefore the standard difference = 0.84

A nomogram (Altman 1999) was used to calculate the sample size with the study

being power set at 0.95. The sample size for the study was 72 patients to be

randomised into two groups.

2.1.3 Patient Groups

List of suitable patients were compiled from a thorough and systematic search of

duplex ultrasound reports and waiting list databases for varicose vein surgery. A

further source of patients with venous disease was the one stop varicose vein clinic at

which all newly referred patients with varicose veins were assessed by the vascular

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nurse specialist. If symptoms and signs of varicose veins existed, DU assessment was

performed at the same clinical appointment.

Prior to inclusion on to the waiting list, all patients had been reviewed by the same

consultant vascular surgeon and had a pre-operative duplex ultrasound scan of their

legs. The duplex scans were individually reviewed and all patients with Small

Saphenous Vein (SSV) reflux, deep venous incompetence, recurrent Varicose Veins

(VV), venous ulceration or lack of incompetent calf perforator veins were excluded.

The exclusion and inclusion criteria used were as follows:

Inclusion Criteria (all of the following need to be present)

-Duplex proven incompetent perforating veins on medial or posterior aspect of

lower leg.

-Isolated great saphenous reflux in patients with primary varicose veins.

-Patient able to give fully informed consent.

(In bilateral cases, one leg was randomised to one group with the other leg

automatically entered in to the other group).

Exclusion Criteria (presence of any of the following would exclude the patient)

Patients unable to give fully informed consent.

Patients with Duplex proven deep venous reflux or occlusion.

Venous ulceration.

SSV reflux

Essentially all patients with Sapheno-Femoral Junction (SFJ) incompetence. Great

Saphenous Vein (GSV) reflux and IPV in the calf were considered for the trial. All

such patients received a postal patient information sheet (appendix 1) outlining the

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trial and its risks. Each patient was also sent a stamp addressed envelope to return

stating whether they would like to take part or arrange an appointment for further

information (appendix 1). Those who responded positively were then contacted and

individual appointments made to discuss the project. All questions were answered at

these meetings and a consent form signed. The patient’s waiting list card was then

marked as a trial patient. A pro-forma (appendix 1) was completed for each patient

and base line tests were performed. These tests were performed in a standard fashion

and a pro forma completed for each aspect. The tests were as follows:

-Repeat duplex ultrasound (if >6m since last scan or performed by other

technologists)

-Photoplethysmography PPG

-Assessment of gait

-Quality of life questionnaires (SF 36 and Aberdeen questionnaire (AQ))

-Visual analogue score

As well as the above, information was collected with respect to:

-CEAP classification for each patient

-Duration of symptoms

-Risk factors including BMI

These patients were monitored as they moved up the waiting list. On the day of their

admission for surgery, each patient was randomised to High Saphenous Tie and Strip

and multiple avulsions (HST&S) alone or HST&S plus SEPS. A random number

table was used to assign each leg to the appropriate group (Altman 1999). Both

groups also had multiple avulsions as appropriate. A consent form was then signed

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and a standardised surgical procedure carried out. It was denied inappropriate for the

patients to be blinded as they had to consent to the procedure. Also it although the

assessors were blinded to whether or not the the patients had undergone SEPS, the

ragiographer was not since the SEPS clips are easily visible on DU.

2.1.4 Operative Intervention

Interventions were randomised into:

Either:

A - High saphenous tie, strip to below knee and multiple avulsions of visible veins.

Or:

B - High saphenous tie, strip to below knee and multiple avulsions of visible veins

and SEPS using the coordinates of the IPV as found on pre-operative DU.

On the day of the operation each patient was consented for the procedure and

underwent a standard general anaesthetic as preferred by the attending anaesthetist.

The patients were positioned supine with their legs abducted and resting on a venous

board. The legs were prepped and draped in the usual manor.

Surgery was performed using standardised methods described below. Post-operative

bandaging consisted of a layer of cotton wool and a layer of firmly applied panelast,

which remained undisturbed until the one week follow-up.

2.1.4.1 High Tie and Strip

A transverse skin crease incision was made medial to the femoral pulse. The

dissection is deepened and the GSV identified and pursued until the SFJ. The

common femoral vein is then identified and all its tributaries around the SFJ ligated in

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continuity with 3/0 prolene. The tributaries at the sapheno-femoral junction are then

dissected out and severed and tied in a similar manor.

The SFJ is then divided between two clips and the proximal SFJ is suture ligated with

3/0 prolene.

The cribriform fascia is then closed with 3/0 prolene and a flexible stripper introduced

into the proximal end of the GSV. The stripper is fed down to the level just below the

knee and the proximal end is ligated to the stripper with a long length of vicryl. The

GSV is then stripped via a small distal incision below the knee thereby insuring the

inversion of the vein during the stripping process. If the vein were to snap during

stripping, the vicryl suture is used to re-introduce the stripper and the vein stripped,

this time with the appropriate head attached to the stripper.

The groin incision is then closed with 3/0 vicryl and the skin incision with sub­

cuticular 3/0 prolene.

2.1.4.2 SEPS

If SEPS was requires a pneumatic tourniquet (Boazul or Ludquvist, fig 11) was rolled

up to the thigh and inflated to a pressure of 120 mmHg, thereby acting as an arterial

and venous tourniquet.

The coordination of the perforators were marked on the calf and a vertical 2 cm

incision made in a suitable position to access the perforators (usually 2 cm posterior to

the tibial edge). The SEPS scope (Olympus/Keymed), is then inserted into the

subfascial plane developed by the operator’s finger (fig 12). Two self closing 5mm

Allport clips (Ethicon Endosurgery), are applied in continuity to each IPV (refer to

fig. 8, 9 and 10) and the vein is not divided. On completion the skin was closed with

sub-cuticular 3/0 prolene.

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Figure 11 SEPS procedure

Figure 12 SEPS procedure

103

2.1.4.3 Avulsions:

Incisions near the varicosities were made with a beaver blade and phlebectomy hooks

were used to avulse the dilated veins. All incisions were closed with steristrips.

Anticoagulation: 5000 iu subcutaneous heparin (unfractionated) at end of

operation.

Post-operative bandaging: Cotton Panalast for one week.

Variables measured during the operation:

1. Time of operation - HST time, SEPS time and Total time.

2. Blood loss - weighing of swabs.

3. Number of avulsions performed.

Patient recovery

The factors measured to assess patient recovery were:

-Analgesia requirement.

-Visual analogue score for pain and mobility.

-Return to work/normal and personal diary to assess patient “cost” of the procedure.

All patients were given a diary (appendix 1) to complete on each post operative day

for 14 days. On a daily basis, they were asked to document the number and type of

pain relief taken along with the number of episodes of assistance they required to

carry out their normal daily work, which would otherwise not be needed. They also

completed a visual analogue score for pain and mobility on each day. At the 6 week

follow-up appointment each patient was asked the number of days they had taken off

work or before they could resume normal activity.

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2.1.5 Outcome

All patients were followed up with appointments made for 1 week, 6 weeks, 6 months

and 1 year post operatively. At each follow up visit a proforma was completed for

each patient following repetition of the tests undertaken pre-operatively.

Criteria measured:

-Presence of any venous reflux measured by duplex ultrasonography

-Improvement in function measured by refill time by means of

Photoplethysmography.

-Time to walk a fixed distance

-Patients opinion on cosmetic results (Visual analogue score)

-Patients opinion on pain (Visual analogue score)

-Patient opinion on mobility (Visual analogue score)

-Quality of life questionnaires (SF36 and Aberdeen questionnaires)

End point:

Follow up at one year from date of operation.

2.1.6 Assessment

Once the patients had agreed to partake in the trial, a standard form was completed for

each patient (appendix 1). Included on this form were patient characteristics and

contact details, history of their VV and their general health, assessment of their risk

factors and symptoms, CEAP classification, gait assessment, DU findings and

Photoplethysmography assessment (appendix 1). Patients also completed visual

analogue score forms as well as quality of life questionnaires (Aberdeen and SF36

Questionnaire).

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2.1.6.1 Visual Analogue Score (VAS)

The visual analogue score took the form of a 10 cm line along which the patients were

invited to make a mark corresponding to the aspect of the affected leg being tested on

the scale. The three VAS were with respect to pain, mobility and cosmetics.

PAINNo Pain At All

The Most Severe Pain I’ve Ever Felt

MOBILITYFull Mobility Without Restriction

I am Unable to Move At All

COSMETIC VIEW OF LEGI am perfectly happy with the Cosmetic Appearance of my Leg

My Leg Could Not Look Worse Than It Does Now

Visual Analogue Scores

Pain % Mobility % Cosmetic View %

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The VAS was completed by each patient at each visit to the hospital (recruitment

meeting, 1 week, 6 weeks, 6 months and 12 months). Also the Pain and Mobility

scores were assigned by each patient for the 14 days following surgery (patient diary

appendix 1).

2.1.6.2 Gait

A segment of corridor in the outpatients department was measured out (30 meters)

and each patient was invited to walk this distance at a leisurely pace. They were timed

performing this task at each visit. An objective assessment of their gate was initially

made however this was found to be irreproducible and subjective between the 3

investigators collecting the data.

2.1.6.3 QOL

Each subject completed a self-completed anglicised SF36 form (Baker et al. 1995,

Brazier et al. 1992), and an Aberdeen questionnaire at each visit. The Aberdeen

questionnaire was used in this study since at time of conception, it was the only

questionnaire validated fo use in the UK with respect to Varicose veins.

Subjects with bilateral legs in each trial were asked to complete a separate Aberdeen

questionnaire for each leg. The participants were advised on how to complete the

form and asked to complete it fully. Any queries from the patients were answered

generally without leading the patient towards a specific answer but enabling an

informed answer.

Each dimension of the SF36 questionnaire was scored separately and out of 100. On

all scales, the higher scores represent a better health. The questions on the Aberdeen

107

questionnaire were weighted and scored by a consultant vascular surgeon who

assessed the contribution of the content to the severity of the disease. In this respect

high scores represent worst symptoms.

2.1.6.4 Duplex Ultrasound

All duplex ultrasounds (Siemens Sonoline Antare, Version 3, Siemens Medical

solutions, Berkshire, UK) performed throughout this study were performed by the

same senior vascular technologist following a standard protocol. A pro forma was

completed for each patient on each visit (appendix 1). All patients who had not been

scanned by our vascular technologist, or who had had a DU study longer than six

months previous to recruitment, were re re-scanned.

With the patient erect the SFJ is scanned in cross section using colour flow duplex.

The probe is applied to the skin and the angle and Doppler gate adjusted to gain

optimum pictures from the system. Standardised Valsalva manoeuvre (Baker et a l

1993) along with sequential manual thigh and calf compression (Sarin et a l 1994) are

performed to assess reflux in the deep and superficial systems along the axial veins of

the leg. Reflux is defined as abnormal flow of blood which lasts longer than 0.5sec in

all veins (Sarin et a l 1994, Van Bemmelen et a l 1989).

The patient is asked to perform a val salva manoeuvre or a calf squeeze test is

perform to exhibit reflux at the SFJ. If a doubt exists regarding the outcome spectral

Doppler settings are used. Using the above manoeuvres the length of the GSV is

scanned and all other dominant and refluxing tributaries which arise from the groin

and the GSV. Deep venous competence is then looked for by scanning the deep veins

in turn.

108

The SSV is found in proximal calf in transverse views and the probe rotated

longitudinally and checked for reflux. The SSV may be of a Giacomini variant and is

scanned through out its course. With the patient in the sitting position on the edge of

an elevated examination bed, the calves are then examined for IPV. In the transverse

section the deep fascia is followed up and down the leg, looking for veins which cross

this fascia. Each is then examined for reflux (blood flowing from the deep system in

to the superficial system which lasts >0.5s). The IP Vs are marked and distance

measured from above the medial and lateral malleolus and the anterior subcutaneous

boarder of Tibia. All anatomical variations are noted throughout the examination.

The specific segments scanned for reflux are outlined in appendix 1.

2.1.6.5 Photoplethysmography (PPG)

All PPG were performed in a standard fashion in a sitting position (Abramowitz et al.

1979, Norgren 1988, Pearce et al. 1983, Rosfors 1990) with the legs in a non weight

bearing position. The patient was asked to sit on the front edge of the seat and lean

back in to the back support of the seat. The knees are positioned at 45 degrees to the

horizontal, so that the feet are comfortably rested on the floor.

The PPG sensor (The Dopplex, Assist Range, Huntleigh Diagnostics) was attached a

distance of 5 cm above the medial malleolus of the affected limb by means of a

transparent adhesive film. Once the test is started, a base line steady trace is first

achieved during which the patient is asked to remain as relaxed as possible. When a

steady trace is reached the 10 second period of exercise begins with a bell emitted

from the machine which is repeated at intervals of one second. Simultaneously with

each bell, the patient performed toe raises. At the end of this period the patient is

109

asked to completely relax all muscles and sit still within the chair with the foot resting

on the ground. The tracing is continued until the baseline is reached once again.

This data was recorded on the memory of the machine and was connected to a simple

printer for hard copies of the graphs representing the changes observe. Each graph had

a time scale axis using which a value of RT90 (90% of refilling time) for each test

was calculated and recorded (Nicholaides & Miles 1987, fig. 7)

2.1.6.6 Data Collection

All data for each patient was tabulated and compiled into an Excel spreadsheet. Once

completed, ten random subjects were chosen and the data input double checked to

ensure there were no mistakes during the data input process. The differing aspects of

the data were then divided into smaller spreadsheet and the results of the NSEPSG

(non SEPS group) and SEPSG (SEPS Group) compared.

The patients were all recruited and had their pre-operative assessment and consenting

performed by the investigator. The bulk of the follow-up data was collected by myself

with the help of two additional colleagues who were trained to carry out the

assessments and data collection (vascular nurse specialist and senior vascular

technologist).

2.1.6.7 Statistical Analysis

All the data collected in the pro-forma were entered into a Microsoft Excel database

(Microsoft Corporation, USA). The data were exported into SPSS (Statistical Package

for the Social Sciences, Version 2003, SPSS Incorporated, Chicago) and analysed.

110

The significance of the differences between the two groups with respect to parametric

quantitative data (e.g. Age, BMI, Surgical time, pregnancy, days off work) was

analysed using unpaired t-test. Chi-square test was used to assess non parametric

qualitative data (categorical data e.g. family history, standing, hospital stay, presence

of IPV) and Mann-Whitney U test was used for ordinal and ranked non parametric

data ( VAS, QOL, PPG). One way analysis of variance was also used to test these

data, and displayed in separate tables.

Wilcoxon Signed Ranks Test was used to assess significance of changes observed in

each group over the 1 year follow-up period. One sample t-test was used to compare

the pre-operative SF36 scores with the mean population score (Baker et al. 1995,

Brazier et al. 1992). For all analysis P values calculated were considered to be

significant if below 0.05 in a two sided test.

During the course of the study two subjects in the NSEPSG were excluded. One

withdrew from the study and the other underwent SEPS even though she was

randomised to the NSEPSG. As these two patients (both from the NSEPSG) were the

only drop outs in the study, it was decided to exclude them rather than treat them as

intention to treat, as they would have little significance due to the small numbers.

I l l

2.1.6.8 Summary of Outcome Measures

Pre-operatively:

Duplex Ultrasonography

Photography of leg in standard position and in standard lighting.

Photoplethysmography (PPG)

SF 36 and Aberdeen quality of life questionnaires

Visual analogue score - Pain, mobility, cosmetic view of leg

Observation of gait and time to walk 30metres at own pace

Operatively

Length of operation - Split into SEPS and total procedure.

Total time in theatre

Blood loss - weighing of swabs

Number of avulsions performed

Hospital Stay

Patient diary for 14 days, includes:

Visual analogue score - Pain and mobility

Analgesia use

Length of hospital stay - Time and date medically able to leave

Time and date actually left

Reason for any difference

112

1 week post-op

Duplex ultrasound

Photography of leg in standard position and in standard lighting.

Photoplethysmography (PPG)

SF 36 and Aberdeen quality of life questionnaires

Visual analogue score - Pain, mobility, cosmetic view of leg

Observation of gait and time to walk 50 metres at own pace

6 week post-op

Time to return to work.

Diary of home assistance required after discharge.

Duplex ultrasound

Photography of leg in standard position and in standard lighting.

Photoplethysmography (PPG)

SF 36 and Aberdeen quality of life questionnaires

Visual analogue score - Pain, mobility, cosmetic view of leg

Observation of gait and time to walk 50 metres at own pace

6 months

Duplex ultrasound

Photography of leg in standard position and in standard lighting.

Photoplethysmography (PPG)

SF 36 and Aberdeen quality of life questionnaires

Visual analogue score - Pain, mobility, cosmetic view of leg

Observation of gait and time to walk 50 metres at own pace

113

1 year

Duplex ultrasound

Photography of leg in standard position and in standard lighting.

Photoplethysmography (PPG)

SF 36 and Aberdeen quality of life questionnaires

Visual analogue score - Pain, mobility, cosmetic view of leg

Observation of gait and time to walk 50 metres at own pace

114

3 CHAPTERS

3.1 RESULTS

N=38 DU at 1 year

223 PATIENTS CONTACTED

SEPSGN=38

N= 32 DU at 1 year

NSEPSGN=34

23 DID NOT RESPOND

41 DECLINED TO TAKE PART

159 AGREED TO TAKE PART

2 Excluded (I wrong procedure I declined surgery)

N=89 72 RECRUITED

DEPENDING ON ORDER ON

WAITING LIST

N=7042 HAD OPERATION 7 NO IPV 6 RECURRENT W 6 NOSFI4 SSV INCOMPETENCE 3 ULCERATION 2 LATER DECLINED

Table 1 Consort table showing flow o f participants.

115

3.1.1 Patients

A total of 223 patients who fitted our inclusion criteria were contacted. Three patients

were recruited directly from our one stop varicose vein clinic and took part in the trial.

In all 220 patients were contacted by mail, of which 90% replied. Approximately 10%

(23) did not respond. These 23 patients were written to a second time with no effect.

Forty one patients responded negatively and were not considered further.

Of the 156 patients who responded positively:

-42 had already had the procedure

-7 had no perforators on repeat scans

-6 were recurrent varicose veins

-6 had no sapheno-femoral incompetence on repeat scans

-4 had developed small saphenous vein incompetence on repeat scans

-3 had developed ulceration

-2 decided not to proceed to operation

-86 deemed suitable for trial of which 69 proceeded to be included. These and the

other 3 patients recruited from the one stop varicose vein clinic made a total number

of 72 patients. Random number tables were used to assign these patients to undergo

High Saphenous Tie and Strip and multiple avulsions (HST&S) with subfascial

endoscopic perforator surgery (SEPSG) or without SEPS (NSEPSG) as their operative

intervention. The patients were recruited from July 2000 and the I year follow up was

completed in April 2004.

All 100 % of patients completed their follow-up. Two patients in the NSEPSG were

excluded:

-One patient withdrew just before the operation

116

-One patient underwent the wrong procedure. It was felt that due to being the only

patient in the study to have been excluded for this reason, it would make little

statistical difference if the patient was treated as intention to treat.

The characteristics of the patients in each group are summarised in table 2. The

SEPSG contained 38 patients with a mean age of 51.1 years old and a male to female

ratio of 1.7. The corresponding figures in the NSEPSG were 32, 49.9 years and 0.8.

The difference for the varied distribution of the males and females in each group is

unaccounted for as the procedure of allocation was random.

Table 2 Demographics o f the two groups (SEPSG - Subfascial Endoscopic Perforator Surgery Group, N S E P S G -N on Subfaseial Endoseopie Perforator Surgery Group, SD one standard deviation, t-test performed for the P values indieated below, non were signifieant)

SEPSG NSEPSG P VALUEAge (SD) 53.4(15.0) 50.4(15.1) 0.87Male 23 13Female 15 19

Mean no. of pregnancies 2.6 2.3 0.529BMI female (SD) 27.9(4.1) 27.9 (6.4) 0.994BMI male (SD) 28.5 (15.0) 29.0(15.1) 0.747Duration of symptoms in yeas (SD) 17.6 (12.3) 18.2 (18.2) 0.86

3.1.2 Data Collection

The over all response rates and data collection rate was good with the exception of the

VAS collected at one week, which were mostly uncompleted. This may be due to the

fact that the patients were already completing their diaries during this period and may

117

have felt this to be duplication. All the collected data were compiled into spreadsheets

for assessment. Table 3 shows a summary of the completed data available on the

databases.

Table 3 Response rate and completion rate of data eollection

Data collected Response rate in SEPSG Response rate in NSEPSGBMI 31/38 (82%) 27/32 (84%)CEAP Classification 38/38 (100%) 32/32 (100%)Days off 27/38 (71%) 22/32 (69%)Diary 38/38 (100%) 32/32 (100%)Duration of symptoms 38/38 (100%) 32/32 (100%)Family history 38/38 (100%) 32/32 (100%)Photoplethysmography 38/38 (100%) 32/32 (100%)Standing 38/38 (100%) 32/32 (100%)VAS at Iweek 18/38 (47%) 19/32 (59%)VAS at 6 weeks 38/38 (100%) 32/32 (100%)VAS at 6 months 38/38 (100%) 32/32 (100%)VAS at 1 year 37/38 (97%) 30/32 (94%)Gait 38/38 (100%) 32/32 (100%)Aberdeen questionnaire (mean of the follow-up) 35.4/38 (93.2%) 28.6/32 (96.5%)SF 36(mean of the follow-up) 34.6/38 (91.0) 29.6/32 (92.5%)Surgery data 31/38 (82%) 27/32 (85%)

3.1.3 CEAP Classification

The CEAP classification was documented for each patient on their pre-operative

assessment by means of ticking the appropriate box on the proforma (Appendix 1).

Figure 13 is a graphical representation of the incidence of the different classifications

in the two groups. All patients had primary varicose veins (Ep), superficial and

perforator incompetence (Aap) and their pathology was as a result of reflux (Pr).

118

SEPSG ■ NSEPSG

No. of patients

CO C1 C2 C3C EA P C lassification

C4 C5

Figure 13 Chart depicting the distribution of clinical classification (CEAP) in SEPSG and NSEPSG.

3.1.4 Duration of Varicose Veins

Information was also collected with respect to the duration of presence of varicose

veins. Each patient was asked to estimate the duration they had been aware of their

varicosities. All patients had symptomatic varicose veins which were present for a

minimum of 1 year. The duration of symptoms were divided into decades and

depicted graphically in Fig. 14.

119

No. of patients SEPSG ■ NSEPSG

1-10 yrs 11-20 yrs 21-30 yrs 31-40 y rs 41-50 yrs

No. o f yrs V V p resent

Figure 14 Bar chart showing the distribution of number of years with varicose veins.

3.1.5 Family History

Enquiries with respect to family history of varicose veins were also made. The most

common finding was that of first degree relatives who also had varicose veins

(fig. 15). There was no significant difference the two groups (Chi Square test P=

0.646) with respect to family history.

120

SEPSG ■ NSEPSGNo. of patients

No Fhx First D egree

Family history

second d egree

Figure 15 Distribution of positive family history in the two groups of patients.

3.1.6 Standing

Each subject was asked to estimate the number of hours they would spend standing

during the course of their average day. These were divided into 1-2 hours, 3-4 hours

or 5-6 hours spent standing in the course of a normal day. The distribution of these

estimations by the patients had been depicted graphically (fig.l6).The two groups

gave comparable responses which were not significantly different (Chi Square test P=

0.197).

121

No. of patients

30

SEPSG ■ NSEPSG

1-2 Hours 3-4 Hours

No. hours stand ing

5-6 Hours

Figure 16 Estimated number of hours standing during the day by each patient in the 2 groups.

3.1.7 Surgery

Table 4 summarises the available operative data collected for each patient. This

includes time taken for HST&S, number of avulsions, total time of the operation and

the time taken for the SEPS procedure in the two groups (the was a large amount of

data missing in this part of the protocol due to the researchers not being able to be

present at all operations and the filling in of the protocol sheet was then left to the

staff present. The times for SEPS procedure were not included since in the majority of

the cases this data was missing). The difference in the total operating time in the two

groups is significantly different and is assumed to be due to SEPS. There were no

statistically significant differences in the two groups with respect to the other data

outlined in table 4 .

122

Table 4 Summarising the operative data gathered. * statistically significant, M=missing data)

No

HST TIME

(min.)

No. Avulsions Total Time

(min.)

Blood loss

(ml.)

SEPSG NSEPSG SEPSG NSEPSG SEPSG NSEPSG SEPSG NSEPSG

1 33 M 22 8 41 65 540 196

2 M 15 M 16 M 33 M 296

3 24 40 80 32 105 70 200 150

4 15 M 8 7 45 M 370 139

5 M M 24 26 80 50 85 608

6 M 16 M 21 65 30 349 378

7 M M M M M M M 288

8 M M M 14 M M 288 218

9 M 30 14 15 M 55 218 162

10 18 M 19 24 48 33 167 M

11 M M M 21 M 30 M 79

12 M 30 50 11 105 50 414 340

13 M 16 57 16 120 44 185 14

14 M 21 14 31 55 41 56 150

15 30 60 4 18 45 70 16 50

16 M M 42 15 60 M 130 71

17 M 20 6 26 55 45 74 90

18 M 21 35 17 60 36 M 303

19 40 M 53 36 90 65 236 660

123

No

HST TIME

(min.)

No. Avulsions Total Time

(min.)

Blood loss

(ml.)

SEPSG NSEPSG SEPSG 1 NSEPSG SEPSG NSEPSG SEPSG NSEPSG

20 60 25 24 1 19 70 55 231 180

21 M 20 33 34 65 38 351 100

22 M 25 20 8 60 40 187 64

23 M 20 37 24 105 40 148 115

24 15 42 11 9 40 48 140 231

25 M M 20 16 75 M M M

26 M M 27 39 M 73 M 440

27 20 M 23 38 40 90 100 483

28 M M 29 31 90 65 129 200

29 M 20 M 29 79 45 120 215

30 10 M 8 11 28 35 M 100

31 M M 52 36 65 70 309 242

32 M 20 33 20 60 55 M 338

33 37 21 48 215

34 M M M M

35 M 27 65 177

36 M 30 60 469

37 M 16 65 126

38 M 14 M 106

Mean 27.5 25.9 27.5 21.5 66.3 50.8* 211.6 230.0

(SD)(14.6) (11.7) (17.1) (9.6) (22.3) (15.6) (128) (160)

124

There were no significant differences between the groups with respect to HST time,

No. of avulsion and blood loss during the procedure (t-test, P = 0.764, 0.097, P =

0.629). However on average the total time of the operation in the SEPS group was

increased by approximately sixteen minutes (P=0.004, mean difference 15.5 95% Cl

5.1-25.9).

The majority of patients were treated as a day case. Table 5 summarises the hospital

stay for the patients in the study groups. All bilateral cases were kept in overnight.

Some patients were kept in overnight due to social circumstances and 2 patients had

difficulty controlling their pain once mobile (both bilateral). There were no significant

differences between the two groups with respect to their hospital stay (Chi square

test). However as noted there were a number of missing data in the SEPSG which

were not recorded on the performa and we were unable to obtain.

Table 5 Summarising the hospital stay for the SEPS and NSEPS groups.

Day case 1 night 2 nights Missing

SEPSG 22 (58%) 8 (21%) 3(8%0 5 (13%)

NSEPSG 23 (72%) 5 (16%) 4 (13%) 0

3.1.8 Patient Diary

All patients in both groups returned a completed diary (appendix 1) at the six week

follow-up appointment. A variety of data was documented by each patient in the two

weeks immediately following their surgery. These include visual analogue scores for

125

pain and mobility, amount of daily analgesia required for each patient and occasions

when assistance was requires as a result of the operation.

Patient Diary (day 1-14 post-op.) SEPSG NSEPSG*pVALUE

VAS for Pain (/100)

Day 1 (range) 39.2 (0-80) 39.2 (0-87) 1.00

Day 14 (range) 12.9 (0-90) 9.0 (0-45) 0.71Change over 14 days (range) 25.1(-16-73) 28.3 (-39-65) 0.48

VAS Mobility (/100)

Dayl (range) 48.0 (0-95) 44.5 (0-85) 0.74Day 14 (range) 14.7 (0-74) 8.5 (0-31) 0.53Change over 14 days (range) 33.8 (-15-86) 36.5 (-14-73) 0.56

Pain relief Consumption

Day 1 (range) 3.4 (0-12) 4.6 (1-9) 0.053Day 14 (range) 0.92 (0-8) 0.75 (0-6) 0.94Change over 14 days (range) 2.4 (-2-12) 4.1 (-1-9) 0.02**

Occasions of Assistance requiredDay 1 (range) 0.8 (0-4) 0.8 (0-3) 0.99Day 14 (range) 0.9 (0-5) 0.9 (0-3) 0.28

*Mann-whitney U, ** significance

3.1.8.1 VAS for Pain

There were no appreciable differences between the two groups with respect to day 1,

day 14 scores or the change of the score over the 14 days (table 6). Also the pain

score at 14 days is far lower than the pre-operative pain scores in both groups (mean

pre-operative pain score 25.1/100 in the SEPSG and 28.3/100 in the NSEPSG). This

126

reduces further to 6.3 and 4.3 respectively at 1 year (refer to Follow-up assessment

below).

Figure 17 represents the changes in VAS for pain over the 14 post-operative days in

the two groups. Initially the scores were, relatively high (39.2 out of 100 in both

groups, SEPSG range 0-80, NSEPSG range 0-87) as would be expected. This quickly

drops off to 12.9 in the SEPSG and 9 out of 100 in the NSEPSG by 2 weeks.

■ Mean diary pain score SEPSG Mean diary pain score NSEPSG

VAS for pain (/100)

45.0

40.0

35.0

30.0

25.0

20.015.0

10.0 5.0

0.0

39.2

12.9

1 2 3 4 5 6 7 8 9 10 11 12 13 14Diary day (1-14)

Figure 17 Graphical representation of mean daily VAS for pain during 14 post-operative days as reeorded in the patient diary.

127

3.1.8.2 VAS for Mobility

This score was also completed by each patient for 14 consecutive days following

surgery. The mean daily values for each group are graphically represented in fig. 18.

Once again this value tails off rapidly and is 14.7/100 for the SEPS group and 8.5/100

in the non SEPS group at 2 weeks. These values are similar to the pre-operative scores

for mobility (11.3/100 and 9.0/100 respectively).

VAS for mobility (/100)

■SEPSG -"-NSEPSG

60.048.0

50.0

40.044.5

30.0

lA Z20.0

10.0

1 2 3 4 5 6 7 8 9 10 11 12 13 14Diary day (1-14)

Figure 18 Mean VAS for mobility as recorded in the patient diary.

3.1.8.3 Pain Relief

All patients were discharged on simple analgesia (such as non-steroidal anti­

inflammatory or codeine based tablets). As would be expected (fig. 19) the use of

analgesia dropped off sharply within a few days of the operation and the pattern of

consumption was similar in the two groups with no significant differences between

128

them (table 6). However the reduction in the number of analgesia taken on day 14

compared to day 1 was significantly higher in the NSEPS group (table 6).

Mean No. of Pain reliefe tablets taken

SEPSG NSEPSG

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.02 3 5 64 7 8 9 10 11 12 13 14

Diary day (1-14)

Figure 19 Mean number of daily analgesic tablets taken by each patient as recorded in the patient diary.

3.1.8.4 Assistance

Each patient noted the number of occasions during the first fourteen post-operative

days, when they had required assistance, as a result of their operation which they

would otherwise not have required (fig. 20). These varied from household chores such

as gardening and shopping to personal care such as dressing and doing up shoelaces.

The assistance required was similar in both groups (table 6).

129

No. of times assisstance needed

■SEPSG NSEPSG1.00.90.80.70.60.50.40.30.20.10.0

1 2 3 4 5 6 7 8 9 10 11 12 13 14Diary day (1-14)

Figure 20 Assistance required as patient diary.

130

3.1.9 Follow-up Assessment

The follow-up period extended to 12 months post-operatively. Each patient had a pro­

forma completed at each visit during their follow-up appointments at 1 week, 6

weeks, 6 months and 1 year.

3.1.9.1 Days Off

Number of days off work was noted in the pro-forma at the 6 week follow-up visit. If

the subjects were not employed they were asked to note the number of days before

they could resume normal activities. Figure 21 represents the distribution of the

number of days taken off. In the SEPSG the mean number of days taken off was

20.1 (range 7-49, SD 20.0) and in the NSEPSG 20.8 days (range 6-42, SD 9.4). There

was no significant difference in the two groups with respect to time off work (t-test P

=0.498).

131

No. of patients

8

Days off SEPSG (mean 20.1) ■ Days off NSEPSG (mean 20.8)

1 1 1 1 1 1 ^ 1 1 1 1 1 1 1 11 11 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49

No. of days off post-op.

Figure 21 Graph demonstrating the number of days taken off work/normal aetivity in each group.

3.1.9.2 Visual Analogue Scores (VAS)

Base line VAS were taken from each patient at the initial interview. This consisted of

scores on pain or discomfort, cosmetic appearance and restriction of mobility. The

VAS were repeated at each follow-up visit (1 week, 6 weeks, 6 months and 1 year).

3.1.9.2.1 Pain

There were no significant differences in the pain scores in the two groups during the

follow-up period (Table 7,8).The mean pain score for the two groups pre-operatively

were 25.9 (range 0-95) and 23.0 (range 0-67) out of 100 in the SEPS and NSEPS

group respectively. The highest score during the follow-up period was at one week

and the pain score subsided following this period (fig 22, table 7).There was good

132

correlation between the available 1 week VAS for pain from the patients diaries and 1

week follow-up appointment (SEPS 23.6/100 29.1/100, Pearson eorrelation = 0.626,

p=0.03, NSEPSG 24.9/100 and 30.9/100, respeetively Pearson eorrelation 0.66,

P=0.01) even though the response rate of the 1 week follow-up VAS was low (table

3).

Table 7 Mean visual analogue scores for pain in the SEPSG and NSEPSG during the follow-up period, *Mann-Whitney U.

Follow-up VAS (/100) SEPSG (range) NSEPSG (range) *P VALUEPAIN

pre-op 25.9 (0-95) 23.0 (0-69) 0.96I wk 29.1 (0-75) 30.9 (0-64) 0.646 wks 7.4 (0-75) 8.4 (0-75) 0.946 m 7.7 (0-50) 5.0 (0-31) 0.83I year 6.3 (0-50) 4.3 (0-20) 0.79change over 12 months 19.0 (-40-72) 19.5 (-15-67) 0.87

133

Table 8 Variance analysis for VAS for pain

Sum of Squares df Mean Square F Sig.

VAS pain preop

BetweenGroupsWithinGroupsTotal

35.667

8762.942

8798.609

1

67

68

35.667

130.790

.273 .603

VAS pain 1 wk

BetweenGroupsWithinGroupsTotal

196.908

12086.535

12283.443

1

68

69

196.908

177.743

1.108 .296

VAS pain 6 wks

BetweenGroupsWithinGroupsTotal

15.645

11287.798

11303.443

1

68

69

15.645

165.997

.094 .760

VAS pain 6m

BetweenGroupsWithinGroupsTotal

138.950

9550.901

9689.851

1

65

66

138.950

146.937

.946 .334

VAS pain ly r

BetweenGroupsWithinGroupsTotal

529.809

12031.496

12561.304

1

67

68

529.809

179.575

2.950 .090

M ean VA S (pain ) at

fo llow -up

M ean V AS (pain) at follow-up S E P S G

M ean V AS atfollo-up N SE P SG

35.0

30 .0

25 .0

20.0

15.0

10.0

5.0

0.0Pre-op IWk 6W ks 6M

A ssessm ent period

Figure 22 Mean VAS for pain at follow up visits.

134

At one year, the end point of the trial, the final VAS for pain compared favourably

with the pre-operative values (table 25) and were significantly lowered in both groups

(P <0.001 for both groups ).

3.1,9,2.2 Mobility

The mobility score, observed by VAS, was assessed at the follow-up clinic (table 9,

10). During the follow-up period, the highest scores occurred at the 1 week follow-up

visit (fig.23). These were substantially higher than pre-operative scores and at the 1

year follow-up appointment these scores dropped significantly in both groups (table

25y

Follow-up VAS (/100) SEPSG (range) NSEPSG (range) *P VALUE

Mobility

pre-op 11.1(0-86) 9.0 (0-50) 1.00

1 wk 25.7 (3-67) 30.2 (1-85) 0.66

6 wks 5.2 (0-50) 4.1 (0-50) 0 J66 m 6.4 (0-55) 2.8 (0-25) 0.321 year 6.5 (0-86) 1.8 (0-18) 0.28

change over 12 months 4.6 (40-71) 7.5 (18-48) 0.43

Table 9 Mean visual analogue scores for mobility during follow-up in the SEPSG and NSEPSG, Mann-Whitney U.

135

Table 10 Variance analusis for VAS for mobility

Sum of Squares df Mean Square F Sig.

VAS Mobil, preop

BetweenGroupsWithinGroupsTotal

77.571

18456.342

18533.913

1

67

68

77.571

275.468

.282 .597

VAS Mobil 1wk

BetweenGroupsWithinGroupsTotal

162.955

16178.015

16340.970

1

31

32

162.955

521.871

.312 .580

VAS Mobil 6wk

BetweenGroupsWithinGroupsTotal

21.404

5361.581

5382.986

1

67

68

21.404

80.024

.267 .607

VAS Mobil. 6m

BetweenGroupsWithinGroupsTotal

229.284

8042.919

8272.203

1

67

68

229.284

120.044

1.910 .172

VAS Mobil. 1yr

BetweenGroupsWithinGroupsTotal

361.473

6699.800

7061.273

1

64

65

361.473

104.684

3.453 .068

Mean VAS (mobility) at follow-up

M ean VAS (mobility) a t follow-up S E P S G

M ean VAS (mobility) a t follow-up N SEPSG

35

30

25

20

15

10

5

0Pre-op IW k 6 W ks 6M

Assessment period

1 Yr

Figure 23 Mean VAS for mobility at follow-up visits.

136

3.1.9.2.3 Cosmetic Appearance

The VAS for cosmetic appearance of patients’ legs scored much higher than pain and

mobility. These scores appear to decline steadily during the follow-up period and

stabilise at 6 weeks (fig. 24). There was no significant difference between the two

groups with respect to these scores (table 11, 12) and the improvements at 1 year were

significant in both groups (P < 0.001, table 25).

Table 11 Mean visual analogue scores for cosmetic appearance during the follow-up period in the SEPSG and NSEPSG, * Mann-Whitney U

Follow-up VAS (/100) SEPSG (range) NSEPSG (range) *P VALUE

Cosmesis

Pre-op 55.8 (0-100) 54.4 (0-100) 0.83

Iwk 27.5 (0-63) 38.6 (3-95) 0.22

6 wk 10.1 (0-50) 11.0 (0-52) 0.78

6 m 11.9(0-87) 9.5 (0-79) 0.73

1 year 13.6 (0-60) 9.7 (0-50) 0.44change over 12 months 45.1 (-56-100) 46.2 (-31-10) 0.92

Table 12 Variance analysis for VAS eosmesis

Sum of Squares df Mean Square F Sig.VAS Cosm. Pre-op

Between Groups

Within Groups Total

34.558

80934.60180969.159

1

6768

34.558

1207.979

.029 .866

VAS Cosm. 1wk

Between Groups

Within Groups Total

954.013

26199.86227153.875

1

3031

954.013

873.329

1.092 .304

VAS Cosm. 6wk

Between Groups

Within Groups Total

16.384

16258.86216275.246

1

6768

16.384

242.670

.068 .796

VAS Cosm. 6m

Between Groups

Within Groups Total

97.444

23390.34223487.786

1

6869

97.444

343.976

.283 .596

VAS Cosm. 1yr

Between Groups

Within Groups Total

254.596

16173.22216427.818

1

6465

254.596

252.707

1.007 .319

137

Mean VAS (cosm et.) at

fo llow -up

60

50

40

30

20

10

0

Mean VAS (cosmet.) a t follow-up SE PSG Mean VAS (cosmet.) a t follow-up N SEPSG

Pre-op IWk 6 Wks 6MA ssessm ent period

1 Yr

Figure 24 Mean visual analogue score for cosmetic appearance of legs during the follow-up period.

3.1.9.3 Walking Assessment

The gait and time to walk a measured distance of 30 meters were assessed in all

patients during the follow-up period. Figure 25 summarises the mean walking time for

the two groups. The walking times have remained essentially static apart from a slight

increase at the 1 week follow-up appointment which is to be expected after an

operation.

138

M ean T im e (s) to w a lk 30

m eters

3 5

3 0

2 5

20

1 5

10

5

SEPSG NSEPSG

0Per-op 1 Wk 6 Wks 6 M

A ssessm ent period

1 Yr

Figure 25 Graph representing mean walking times over marked out distance of 30m in the two groups.

3.1.9.4 Quality of Life

The quality of life was assessed by the use of the anglicised SF-36 and Aberdeen

questionnaire (AQ). The questionnaires were completed at the pre-operative

assessment and at each follow-up visit in order to assess the impact of surgery on the

patients well being.

3.1.9.5 SF-36

The patients in both groups had pre-operative scores in all dimensions of the SF-36

which were similar to the general population scores (table 13). One sample t-tests

were performed on all pre-operative scores and all except physical function in the

SEPS group had P values well above 0.05 (range 0.15 - 0.73). The P value for

139

physical function in the SEPS group was 0.034, indicating a significant difference

with the general population values (Brazier et al. 1992, Baker et al. 1995, fig 26 and

27).

There was no statistical difference between the SF36 scores in the two groups during

the course of the follow-up period (table 13, 14). It was not possible to analyse the

Iweek scores for physical function, role physical and role emotional due to missing

data. This data was not fully completed by the patient as a result of missing sheet

following photocopying of the questionnaire. This did not come to the attention of the

researcher until completion of the trial. The Mann Whitney U test P values obtained

for all the other scores were higher than 0.05 when comparing the two groups (table

13). However variant analysis (table 14) did show a significant difference between the

the two groups with respect to pre-operative physical function. There were also no

significant differences in the improvement of the scores over the 12 month follow-up

(P>0.05).

The changes over one year are shown in table 25. In neither group were these

improvements significant except the score improvement for bodily pain in the SEPS

group (P=0.002, table 25).

140

Table 13 Summary o f the mean SF36 scores out o f 100, in the two groups during the follow-up period, (M= Missing Data, * General population data as per Baker et a l 1995, Brazier et al. 1992, $Significant difference from the general population, all other data no significant difference seen between the 2 groups, Mann Whitney U test P>0.05).

SF 36 (/lOO)

* General population Pre- (/lOO) operative IWK 6WK 6M

Change lYR over 1 yr.

General health 71.2SEPSG 69.0 77.5 75.6 71.3 69.8 0.8NSEPSG 70.0 74.8 76.0 72.8 71.2 1.2Physical function 862SEPSG 75.8» M 792 79.8 80.7 4.9NSEPSG 8%5 M 85 5 892 87.4 -0.1Role Physical 822SEPSG 79.4 M 59.0 76.4 81.1 1.7NSEPSG 8&8 M 612 862 90.0 1.2Role emotional 81.6SEPSG 8&5 M 81.5 90.9 91.9 5.4NSEPSG 86.4 M 80.0 902 91.1 4.7Social function 87.0SEPSG 85.4 49.0 79.5 882 87.9 2.5NSEPSG 892 492 822 922 87.1 -2.1Bodily pain 79.0SEPSG 70.5 392 71.9 84.1 822 122NSEPSG 77.0 37.5 69.4 862 852 8.3Vitality 60.8SEPSG 61.1 532 64.7 67.6 68.0 6.9NSEPSG 64.5 50.6 67.0 67.8 66.9 2.4Mental health 72.5SEPSG 76.2 782 80.4 824 75.5 -0.7NSEPSG 75.7 72.0 822 80.7 77.7 2.0

141

Table 14 Representing the variance analysis carried out with respect to SF36 scors,* statistical significance

Sum of Squares df Mean Square F Sig.

SF36 1 PRE General Health

Between Groups

Within Groups Total

15.565

21957.50021957.500

1

6061

15.565

365.699

.043 .837

SF36 1 1WK General Health

Between Groups

Within Groups Total

114.249

12968.60913082.857

1

6162

114.249

212.600

.537 .466

SF36 1 6WK General Health

Between Groups

Within Groups Total

2.582

18320.46718323.048

1

6061

2.582

305.341

.008 .927

SF36 1 6M General Health

Between Groups

Within Groups Total

31.833

23320.65023352.484

1

5960

31.833

395.265

.081 .778

SF36 1 1YR General Health

Between Groups

Within Groups Total

27.512

33007.799 33035.311

1

5758

27.512

579.084

.048 .828

SF36 3 PRE Phys. Function

Between Groups

Within Groups Total

2166.130

31007.55533173.684

1

6263

2166.130

500.122

4.331 .042*

SF36 3 6WK Phys. Function

Between Groups

Within Groups Total

630.064

26153.93626784.000

1

6162

630.064

428.753

1.470 .230

SF36 3 6M Phys. Function

Between Groups

Within Groups Total

1575.837

39615.30241191.138

1

6364

1575.837

628.814

2.506 .118

SF36 3 1YR Phys. Function

Between Groups

Within Groups Total

703.607

28006.40228710.009

1

6162

703.607

459.121

1.533 .220

SF36 4 PRE Role Phys.

Between Groups

Within Groups Total

1377.419

58820.99460198.413

1

6162

1377.419

964.279

1.428 .237

SF36 4 6WK Role Phys

Between Groups

Within Groups Total

76.269

105923.731106000.000

1

6364

76.269

1681.329

.045 832

142

Sum of Squares df Mean Square F Sig.

SF36 4 6M Role Phys

Between Groups

Within Groups Total

1785.973

109888.165111674.138

1

6364

1785.973

1744.257

1.024 .315

SF36 4 YR Role Phys

Between Groups

Within Groups Total

1255.772

60787.87962043.651

1

6162

1255.772

996.523

1.260 .266

SF36 5 PRE Role Emot.

Between Groups

Within Groups Total

.022

49152.52149152.542

1

5758

.022

862.325

.000 .996

SF36 5 6WK Role Emot

Between Groups

Within Groups Total

35.915

73432.09973468.013

1

6465

35.915

1147.377

.031 .860

SF36 5 6M Role Emot

Between Groups

Within Groups Total

.169

44820.62044820.789

1

6061

.169

747.010

.000 .988

SF36 5 1YR Role Emot

Between Groups

Within Groups Total

10.261

39919.19239929.453

1

6162

10.261

654.413

.016 .901

SF36 6 PRE Social func.

Between Groups

Within Groups Total

234.432

21943.45222177.885

1

6364

234.432

348.309

.673 .415

SF36 6 1WK Social func.

Between Groups

Within Groups Total

.922

55097.02655097.948

1

6566

.922

847.647

.001 .974

SF36 6 6WK Social func.

Between Groups

Within Groups Total

125.433

41539.67941665.112

1

6566

125.433

639.072

.196 .659

SF36 6 6M Social func.

Between Groups

Within Groups Total

219.848

30246.49830466.346

1

6364

219.848

480.103

.458 .501

SF36 6 1YR Social func.

Between Groups

Within Groups Total

9.984

22802.51622812.500

1

6162

9.984

373.812

.027 .871

SF36 7 PRE Bodily Pain

Between Groups

Within Groups Total

672.537

38209.71038882.246

1

6364

672.537

606.503

1.109 .296

SF36 7 1WK Bodily Pain

Between Groups

Within Groups Total

75.887

30556.22330632.109

1

6263

75.887

492.842

.154 .696

143

Sum of Squares df Mean Square F Sig.

SF36 7 6WK Bodily Pain

Between Groups

Within Groups Total

97.152

28304.91028402.062

1

6364

97.152

449.284

.216 .644

SF36 7 6M Bodily Pain

Between Groups

Within Groups Total

114.603

21587.71421702.317

1

6162

114.603

353.897

.324 .571

SF36 7 1YR Bodily Pain

Between Groups

Within Groups Total

99.491

26415.49326514.984

1

6162

99.491

433.041

.230 .633

SF36 9A PRE Vitality

Between Groups

Within Groups Total

138.544

17406.07117544.615

1

6364

138.544

276.287

.501 .481

SF36 9A 1WK Vitality

Between Groups

Within Groups Total

114.624

22784.24022898.864

1

6465

114.624

356.004

.322 .572

SF36 9A 6WK Vitality

Between Groups

Within Groups Total

84.396

19577.14319661.538

1

6364

84.396

310.748

.272 .604

SF36 9A 6M Vitality

Between Groups

Within Groups Total

404.774

33199.16533603.939

1

6465

404.774

518.737

.780 .380

SF36 9A 1YR Vitality

Between Groups

Within Groups Total

19.841

21417.65921437.500

1

6061

19.841

356.961

.056 .814

SF36 9B PRE Mental Health

Between Groups

Within Groups Total

3.100

14352.83814355.938

1

6364

3.100

227.823

.014 .908

SF36 9B 1WK Mental Health

Between Groups

Within Groups Total

631.930

13391.60014023.530

1

6465

631.930

209.244

3.020 .087

SF36 9B 6WK Mental Health

Between Groups

Within Groups Total

95.275

9000.9719096.246

1

6364

95.275

142.873

.667 .417

SF36 9B 6M Mental Health

Between Groups

Within Groups Total

46.393

8712.6078759.000

1

6263

46.393

140.526

.330 .568

SF36 9B 1YR Mental Health

Between Groups

Within Groups Total

37.029

13792.68613829.714

1

6162

37.029

226.110

.164 .687

144

SEPSG pre-op -hk—NSEPSG pre-op. -^N S E P S G 1yr

100.090.080.0

T- 70.060.0

50.040.030.020.0 10.0

0.0

Li.w

Figure 26 Figure showing the mean scores o f the SF-36 dimensions pre-operatively and at one year for the SEPSG and NSEPSG as well as the mean values representing the general population.

General population SEPSG 1 yr -4K- NSEPSG 1 yr

100.090.080.0

T- 70.060.050.040.030.020.0 10.00.0

oo

ou(A<o«?LL(0

Figure 27 Figure showing the mean scores of the SF-36 dimensions pre-operatively and at one year for the SEPSG and NSEPSG as well as the mean values representing the general population.

145

3.1.9.6 Aberdeen Questionnaire

Table 15 and 16 summarises the Aberdeen questionnaire score in the two groups and

analysis of variance respectively. The mean scores during the follow-up period have

been graphically represented in figure 28.The only significant difference between the

two groups was observed at week one with the SEPSG mean score of 23.4 versus 18.2

in the NSEPSG (P<0.05). This implies more perceived symptoms in the SEPS group.

ABERDEEN (/ICO) SEPSG NSEPSG *P VALUE

PRE-OP 19.1 15.5 0.108

IW EE K 23.4 18.2 **0.041

6 WEEKS 16.1 11.2 0.204

6 MONTHS 8.4 6.2 0.35

1 YEAR 9.0 5.8 0.128

CHANGE OVER lYR 10.8 9.1 0.37

Table 15 Mean Aberdeen questionnaire score for the two group, *Mann whitney U, ** significant

The scoring of the questionnaire at 1 weeks was adjusted to the conventional score as

the diagrammatic section of the questionnaire was not completed by the patients. This

was due to the standard post-operative care of the patients which involved bandaging

of the operated legs for 1 week. Because of this the patients were not able to complete

the diagrammatical part of the questionnaire. The scores for this were hence adjusted

to exclude the scores for the diagram for all patients. There were significant

improvements in the Aberdeen questionnaire scores over the 12 month period in each

group (P <0.001 in both groups, table 25).

146

Sum of Squares df Mean Square F Sig.

Aberdeen pre Between Groups Within Groups Total

215.8074656.4924872.299

16566

215.80771.638

3.012 .087

Aberdeen Iwk Between Groups Within Groups Total

482.4075858.5796340.986

16869

482.40786.156

5.599 .021*

Aberdeen 6wk Between Groups Within Groups Total

439.15617103.929

17543.086

168

69

439.156251.528

1.746 .191

Aberdeen 6m Between Groups Within Groups Total

78.8083070.6923149.500

16869

78.80845.157

1.745 .191

Aberdeen 1yr Between Groups Within Groups Total

165.0053630.2293795.234

16263

165.00558.552

2.818 .098

Aberdeen change overlyr

Between Groups

Within Groups Total

49.267

5323.3235372.590

1

5960

49.267

90.226

.546 .463

Table 16 Analysis o f variance for Aberdeen questionnaire,* statistical significance

147

SEPSG -" -N S E P S G

oo

25.0

20.0

15.0

10.0

5.0

0.0PRE-OP 1 WEEK 6 WEEKS 6 MONTHS 1 YEAR

Follow-up

Figure 28 Figure representing the Aberdeen score for the two groups during the follow-up period.

3.1.9.7 Photoplethysmography (PPG)

The mean PPG derived RT90 (90% of refilling time on PPG) times for the two groups

are summarised in table 17. There were no significant differences between the PPG

times in the two groups except at 1 year. However on variant analysis this

significance was not found (table 18). Although both the mean RT90 times were well

within the normal limits, the NSEPSG had a significantly higher RT90 time than the

SEPSG (P=0.04).

Considering each group individually, the mean RT90 values had increased

significantly by 12 months after operation for both groups (P < 0.001 table 25) and

the mean values in both groups were within normal limits (RT90 >18seconds).

148

PPG (secs.) SEPSG (range) NSEPSG (range) *P VALUE

Pre-op. 13.0 (4-45) 14.5 (1-45) 0.96

1 week 31.8 (10-47) 35.2 (1-46) 0.18

6 weeks 27.0 (8-46) 28.8 (11-46) 0.52

6 months 24.9 (10-47) 27.8 (9-45) 0.29

1 year 25.2 (9-47) 30.7( 7-46) **0.04Change over 1 year 13.3 (-17-38) 16.3 (-20-45) 0.42

Table 17 showing the mean RT90 times in the 2 groups during the study, *Mann-Whitney U, ** significant

Table 18 Analysis o f variance for PPG results

Sum of Squares df Mean Square F Sig.

Preop Between Groups Within Groups Total

35.6678762.9428798.609

16768

35.667130.790

.273 .603

One wk ppg Between Groups Within Groups Total

196.90812086.53512283.443

16869

196.908177.743

1.108 .296

Six wk ppg Between Groups Within Groups Total

15.64511287.79811303.443

16869

15.645165.997

.094 .760

Six m ppg Between Groups Within Groups Total

138.9509550.9019689.851

16566

138.950146.937

.946 .334

One yr ppg Between Groups Within Groups Total

529.80912031.49612561.304

16768

529.809179.575

2.950 .090

Change over 1yr Between Groups Within Groups Total

149.66016377.22216526.882

16667

149.660248.140

.603 .440

Figure 29 and 30 are graphical representation of the changes in the individual RT90

values from pre-operative time to 12 months post-operative, in the SEPS and

NSEPSGs.

149

P R E -O P . RT90 IN S E P S G 1Y R R T 90 IN S E P S G

Figure 29 Graphical representation of PPG derived T90 times in secs, for SEPSG (pre-op. and at one year).

45

P R E -O P . RT90 IN N S E P S G 1 YR RT90 IN N S E P S G

Figure 30 Graphical representation of PPG derived T90 times in seconds in NSEPSG (pre-op. and at one year).

150

In all 10 patients had PPG RT90 times which were lower at 1 year than at their pre­

operative assessment (table 19, and Fig 29 and 30). Seven of these were in the SEPSG

and 3 in the NSEPS group. Of these 10 patients, eight were found to have

pathological reflux within the remnant below knee Great Saphenous Veins (GSV),

one being as a result of connection with refluxing accessory GSV which was not seen

on the pre-operative or the 1 week post-operative scan.

Two of these ten subjects (1 SEPSG, 1 NSEPSG) had PPG derived RT90 values at

one year which were only marginally lower then the pre-operative value and were

well within the normal limit of >18 seconds. One other patient had RT90 value at one

year which was within normal limits, although significantly reduced from pre­

operative levels. The remaining 6 (5 SEPSG, 1 NSEPSG) all had pathological values

of RT90 at one year (<18 seconds), and 5 (4 in SEPSG, 1 in NSEPSG) out of six had

reflux within the remnant below knee GSV on duplex ultrasound (DU).

Patientno.

Group Pre-op RT 90 (sec.)

Iwk RT 90 (sec.)

6wkRT90(sec.)

6mRT 90 (sec.)

lyrRT 90 (sec.)

lower 1/2 GSV reflux

IPV at 1 yr

1 SEPS 45 45 45 44 42* No Yes2 SEPS 11 20 13 15 9 No No3 SEPS 27 10 15 28 10 Yes yes4 SEPS 32 32 27 22 18 Yes No5 SEPS 17 45 43 13 15 Yes No6 SEPS 16 44 27 16 13 Yes No7 SEPS 29 21 29 44 16** Yes Yes8 NSEPS 44 45 32 M 24* Yes Yes9 NSEPS 45 45 44 20 44* Yes No10 NSEPS 9 11 11 9 8 Yes Yes

Table 19 Summarising findings in patients with shorter RT 90 at one year compared to pre-operative times. (M=missing, * with in normal limits, **accessory GSV).

151

3.1.9.8 Duplex Ultrasound

All DU studies were carried out by the same senior vascular sonographer throughout

this study. We were fortunate enough to have completed DU scan follow-up in 100%

(n=72) of our patients as per our protocol. All open perforators were noted and

differentiated into new (not present on the pre-operative scan) or same (present on

preoperative scan). Of note was that there were no intact SFJ in either group at 1 week

or 6 weeks which may have represented primary failure of the surgery. In the

NSEPSG there were 2 patients with a second refluxing LS system, one at the 1 week

follow up the other at 6 weeks follow up. In both patients haematoma tracts along the

striped primary LSV were visible on duplex ultrasound.

3.1.9.8.1 Subfascial Endoscopic Perforator Surgety Group (SEPS)

In the 38 patients in the SEPSG, a total of 62 Incompetent Perforator Veins (IPV)

were found on the pre-operative scan (Table 20). At one year, 12 patients (31.5%) had

a total of 19 open IPV (5/62 (8%) same, 14/62 (22.6%) new).

-At the one week scan 2/38 (5.2%) patients were found to have 2 same IPV open

(Table 22). One was found not to be open during the rest of the follow-up. The other

patient’s IPV was seen to be refluxing at 6 months with a second same perforator,

both of which remained open at one year.

-At 6 weeks, one patient (2.6%) had 2 new IPV refluxing which remained open at 6

months and one year.

-At the 6 month scan 8/38 (21%) of patients were found to have a total of 11 IPV

(5/11(45.5%) same, 6/11 (54.5) new). All eight had IPV which were also present at

the 1 year follow-up scan (table 20). Two of these eight patients had developed an

additional new IPV each at the 12 month scan. Of the remaining 4 patients at one year

152

with IPV one had 2 new and 3 others had 1 new perforator without having any other

IPV open during the follow-up period.

Patients with IPV at follow- up (SEPSG) N=38 Pre-op. 1 week 6 weeks 6 months 1 year1 1 ls,ln ls,2n2 1 Is3 1 In In4 2 2n5 4 Is 2s 2s6 1 In7 1 In8 1 In9 1 2n 2n 2n10 3 Is Is.ln11 1 Is Is12 2 In 2n13 1 In In

Total no. of IPVs (n=62 pre-op.) 20 2(% ) 2(2n) 11 (5s,6n) 19 (5s,14n)No. of patients with IPV 38 2 1 8 12

Table 20 summarising the ultrasound findings in SEPSG with respect to IPV. (n = new IPV not seen on the pre-op. DU, s = same perforators as seen on the pre-op. DU).

3.1.9.8.2 Non Subfascial Endoscopic Perforator Surgery Group (NSEPSG)

A total number of 51 IPV were found in 32 patients in the NSEPSG (table 21). IPV

were seen in 25/32 (78.1%) of these subjects at the one year follow-up (table 22), with

a total number of 46 IPV (37/51 (72.5%) same, 9 new)).

At the one week scan 15/32 (46.8%) patients were found to have 25 IPV (23/25 (92%)

same, 2/25 (8%) new). All 15 patients were found to have at least one same IPV

153

refluxing (eight patients had 1, six patients had 2 and one had three same IPV). Two

of these patients had also developed one additional new IPV each.

At six weeks 17/32 (53.1%) patients were found to have 26 IPV (23/26(88.4%) same,

3/26(11.6%) new) on DU. Four new patients had developed 1 same IPV each and one

additional patient had 1 new IPV. In 2 patients, both with 1 same IPV at 1 week, no

IPV were demonstrated at 6 weeks scan. Both these IPV were seen on the 6 month

scan but not at the 12 m scan. One patient with one same and 1 new IPV at the one

week scan had no IPV at the six week scan even though these IPV were found on the

6 month and 12 month scans. Two patients reduced the number of same IPV from 2 to

1 at the six week scan and one patient increased the number of IPV from 1 same to 2

same at 6 weeks. One patient with Isame IPV at 1 week developed an additional new

IPV at six weeks.

At six months 24/36 (58.3%) patients had a total of 37 IPV (30/37(81.1%) same,

7/37(18.9%) new). Ten of these subjects had the same IPV pattern as at the 6 weeks

scan. Four new patients had opened 1 same IPV each and 2 patients had developed a

second same IPV. One of the remaining patients has 1 same IPV at 1 week, developed

an additional new perforator at 6 weeks and a second additional new perforator at 6

months. This pattern remained the same on the 12 month scan. Another patient with 2

same and 1 new IPV at 1 week and 6 weeks had only one same IPV at 6 m and went

on to have 2 same IPV at the 1 year DU. Another subject had 2 same at Iweek, 1

same at 6 weeks and only 1 new at 6m. This patient went on to have all 3 IPV open at

12 months. In another case 2 same IPV seen at the 1 week and 6 weeks scans were

present at 6 months in addition to a new IPV. The one year scan in this patient showed

all 3 pre-operative IPV to be open. One patient was also seen with 1 same IPV at 1

154

week and 6 weeks scans but had developed an additional new perforator at 6m and

went on to develop another new perforator at 1 year.

At the one year scan 25/32 (78.1%) of patients in the NSEPSG had a total number of

46 IPV). Thirteen of these patients had the same duplex pattern as at the 6 month

scan. Three new patients developed 1 same IPV each and one patient with 1 same IPV

at 6 months developed an additional same perforator at 1 year. Two patients

developed an additional 1 same IPV to add to their existing IPV at six months to bring

their numbers to 2 and 3 same IPV. Another patient reduced the number of IPV from

2 at 6 months to 1 at 1 year. One patient developed 1 new perforator at one year as

well as having the existing 1 same and 1 new seen at 6 m. Another patient who had 1

same perforator on the three previous scans developed an additional 2 new perforators

at 1 year.

There were significant differences with respect to the number of incompetent

perforators seen on DU post-operatively in the two groups (table 22).

155

Patients with IPV at follow- up (NSEPSG) N=32 Pre-op 1 week 6 weeks 6 month 1 year1 1 Is Is, In ls,2n Is, 2n2 2 Is 2s 2s 2s3 1 Is4 3 2s, In 2s, In Is 2s5 2 2s Is In 2s, In6 2 Is 2s7 1 Is Is8 3 2s 2s 2s, In 3s9 1 Is Is10 4 Is Is11 3 Is Is Is Is, 2n12 1 Is Is Is Is13 2 Is 2s 2s14 1 Is Is15 2 Is 2s Is16 1 Is Is ls,ln Is, 2n17 2 2s Is Is 2s18 3 2s 2s 2s 3s19 2 Is20 2 Is Is Is21 1 Is Is Is22 1 In In In23 3 Is Is24 3 3s 3s 3s 3s25 1 Is26 1 ls,ln ls,ln ls,ln27 2 2s 2s 2s 2sTotal no. of IPV (n=58 pre-op.)

51(total of 58 IPV pre-operatively)

25

(23s, 2n)

26

(23s, 3n)

37

(30s, 7n)

46

(37s, 9n)No. of patients with IPV 32 15 17 24 25

Table 21 Summarising the ultrasound findings in NSEPS Group with respect to IPV. (n=new IPV i.e. not seen on the pre-op. DU, s = same perforators as seen on the pre-op. DU).

156

Number o f perforators at duplex ultrasound scanpre­op. 1 week 6 weeks 6 months 1 year

IPV IN SEPSG 62

Total same new Total same new Total Sam new Total same New

2 2 0 2 0 2 1 1 5 6 19 5 14No. of IPVremaining competent in SEPSG 60 (97%) 62 (100%) 57(92%) 57 (92%)IPV IN NSEPSG 58 :#* 23* 2 2K* 23* 3 37* 30* 7 46* 37* 9No. of IPVremainingcompetentinNSEPSG 35 (60%) 35 (60%) 28 (48%) 21 (36%)

no. with IPV no. with IPV no. with IPV no. with IPVNo. OFLEGSSEPSG 38 2/38 (5.2%) 1/38 (5.2%) 8/38(21.1%) 12/38(31.6%)No. OFLEGSNSEPSG 32 15/32 (50%)* 17/32 (53.1%)* 23G2(7L8%0* 25/32(78.1%)*

Table 22 Summary o f IPV found on DU in the 2 groups during the follow-up period. * Significant difference between the two groups (Chi square test, P<0.001)

157

SEPSG

N/38Pre-op

1year

**p

Value

NSEPSPre-

N/32 op1year

**p

ValueVAS(/lOO)

Pain

Mobility

Cosmetics

36

36

36

21911.1

5&7

6.3

6.5

13.6

0*

0.041*

0 *

32

30

30

218

9.3

55.9

4.3

1.8

9.6

0*

0 .001*

0*

SF36(/ICO)

Gen Health3Phys.FunctionRolePhysicalRoleEmotionalSocialFunction

Bodily pain

VitalityMentalHealth

26

33

32

29

33

33

32

33

69j

77.2

81.3

815

8A5

69

61.4

719

71.5

80.7

82

94.3

87.9

82.3

67.7

74.9

0.62

0.12

0.91

120

0.34

0 .002*

0J8

0.68

26

28

29

26

29

29

29

28

617

87.1

818

819

818

76.1

64.5

716

718

829

89.7

916

87.1

85.3

66.9

77.7

0.053

0.40

0.78

0.27

0.72

0.10

0.24

0 J7Aberdeen(/ICO)

32 19.6 15 29 15.1 6.1 0*

PPG

RT 90 (sec.) 36 12.1 25.4 0* 32 14.5 (0.7

Table 23 Table summarising the changes observed in Follow-up data in each group during the 1 year follow-up period., ** Wilcoxon Signed ranks tests were performed to assess changes in PPG, QOL and VAS over one year in each group . Those improvements which were statistically significant are marked (*).

158

4 CHAPTER 4

4.1 VENOUS PRESSURE MONITORING

In order to assess the impact of the pressure exerted by the Incompetent Perforator

Vein (IPV) we designed a study to measure the pressure changes observed adjacent to

incompetent and competent perforator veins. In this way we hoped to investigate:

Whether the IPV were associated with higher pressures in the adjacent superficial

system.

At which phase of calf contraction and relaxation does maximum pressures occur and.

If there is an increase in pressure as a result of IPV is it distributed globally or locally

within the superficial system.

Relationship and contribution of IPV to Photoplethysmography (PPG) findings.

Unfortunately despite the kind assistance of Department of Medical Physics at the

university Medical School of St.George’s, the instrumentation did not appear to be

sufficiently sensitive and reliable with respect to the intended procedure and

measurements taken. The results obtained were not reproducible in the same subjects

and no meaningful data which could be interpretated reasonably were obtained in six

out of the required ten subjects. This project was hence abandoned but for

completeness a brief outline of the methodology of the project is given here.

159

4.1.1 Methods and Materials

Our aim was to recruit 10 patients with Sapheno-Femoral Junction (SFJ)

incompetence, 5 with incompetent perforator veins and 5 with competent perforator

veins. These patients were recruited from vascular outpatients and waiting lists.

All patients had pre-operative PPG and ultrasound scan and their venous anatomy and

perforator status documented. The PPGs were undertaken in a standard fashion as

outlined previously (methods and materials). The scans were all performed by the

same senior vascular technologist as the randomised trial and the same protocol was

followed (refer to methods and materials). Subjects with deep venous and small

saphenous vein incompetence were excluded from this study. All patients were to

undergo High Saphenous Tie and Strip and multiple avulsions (HST&S) or venous

ablation by radio-frequency as well as Subfascial Endoscopic Perforator surgery

(SEPS) depending on their perforator status.

On the day of the operation each patient was interviewed and given a patient

information sheet to study. If the patients were agreeable a consent form was signed.

The procedure was undertaken before administration of general anaesthetic in the

operating theatre. The affected leg was rescanned and the Great Saphenous Vein

(GSV) cannulated (20G Abocath) at two positions after administration of 1ml of local

anaesthetic (1% xylocaine). One cannula was placed with in the GSV just above the

medial malleolus, and the other under direct duplex guidance, directly adjacent to the

interested perforator vein. Once in place each catheter was fixed to the skin and the

distance between the catheters noted. The cannula were then connected to a two

channel transducer and the anaesthetic machine. The system was then flushed with

heprinised normal saline and zeroed to the level of the sternal notch with the patient

160

in the supine position. At this point the patient was administered with 200IU of

heparin intravenously to prevent the cannula from thombosing.

The anaesthetic machine was set-up as follows to obtain an analogue output from two

channels:

Setup

Install/service

password

Installation

Analogue

Channel 1 - low resolution PI

Channel 2- low resolution P2

The output from the anaesthetic machine was connected to the parallel port on the

ADC-100. The ADC-100 (picolog for windows, 2003, Pico Technologies LTD) is an

analogue to digital converter with two analogue input channels and programmable

input voltage range. Specially designed connections were provided by the company to

connect the ADC-100 output channels to a parallel port on a laptop computer (Sony

Viao PCG-Z600TEK, Sony Inc., Japan). With the help of Picoscope program and

picoLog software provided and installed on the laptop data in the form of pressure

changes could be viewed as an oscilloscope display on a laptop and all data recorded

in the form of logs for review at a later date. These data included time intervals and

voltage changes which were calibrated initially to represent changes in pressure in

mm Hg.

161

With the use of a three way tap, the transducer plastic piping was initially connected

to a sphygmomanometer and the ADC-100 was calibrated for pressures of up to 100

mmHg. The settings for the converter were as follows:

Sample intervals 10ms

No. of samples 60,000

Voltage range -0.5 2.0 (under options)

The patient was then reconnected to the transducers and asked to lie supine on the

operating table. The output is observed on the laptop screen and once a stable baseline

pressure was attained the subject was asked to perform foot exercises. The

instructions with respect to these exercises were very specific and were accompanied

by verbal prompts. The patient was asked to perform full dorsiflexion at the ankle and

then to return to the resting position. This procedure was performed three times in

succession whilst recording are taken saved on the laptop. It was important to

document and make clear which of the two readings was from the perforator and the

GSV. The patient was then repositioned in a sitting position on the edge of the

operative bed with the legs dependent. The procedure was then repeated and further

recordings taken in this position.

This study was assessed and approved by the Local ethics committee.

4.1.2 Results

This procedure was undertaken in six subjects who had consented to take part in the

study. Recurring problems involved the ineffective damping of the system which did

not prevent background interference from affecting a steady baseline at the beginning

of the procedure. Also once a steady state was reached and reading taken, the patterns

produced by the oscilloscope on the computer screen were not reproducible on

162

repeating the exercises. There w ere also no com m on patterns observed w hen the

reading o f different subjects w ere compared. Figure 31 and 32 are the graphical

outputs recorded on one o f the patients w hich depicts the expected findings during

exercise.

15 n

Time (Seconds)

PI perforator Press. P2 LSV press.

Figure 31 Graphical representation of changes in pressure observed in the foot veins.

D) 2 0

10

1 52Û. 0

I ■ I ^iiP1-P2

10 20 30Time (Seconds)

40

Figure 32 Graphical representation of the difference in the observed pressures.

D ue to tim e constraints it w as not possible to adjust the instrumentation in order to

improve the accuracy and reproducibility o f the system and the project w as

abandoned.

163

5 CHAPTERS

5.1 DISCUSSION

At the end point of this study (1 year following operation), there was a substantial

difference between the numbers of Incompetent Perforator Veins (IPV) in the two

groups on DU (Primary outcome). The NSEPSG (HST&S without SEPS) had a far

higher number of patients and number of IPV at one year (25/32 patients with 46 IPV

vs. I2/38patients with 19 IPV in the SEPSG). Also the majority of these perforators were

the same ones seen on the pre-operative DU (37/46 (80%) vs. 5/19 (26%) in SEPSG).

This dismisses the idea that 80% of IPV are closed at 6 weeks following High

Saphenous Tie and Strip and multiple avulsions (HST&S) (Campbell & West 1995).

In our NSEPSG, 40% of IPV (fig. 33) seen on the pre-operative DU were refluxing at

6 weeks and their numbers increased during the rest of the follow-up period. Table 22

outlines the number of pre-operative perforators which were not refiuxing following

surgery in the two groups. In the SEPSG this number remains consistently above 92%

through out the follow up period with no increase from the 6 month scan to the 12

month scan. In the NSEPSG group however this percentage decreases progressively

to 36% at I year.

164

SEPS (n=62 pre-op)*— NSEPS (n= 58 pre-op)

23 (40%)

No. of sam e 20 IPV 15

10 -

Same at 1 wkSame at 6wks Same at 6m Same at 1 yrFollow-up

Figure 33 Graph showing the no. of same IPV in the 2 groups

However, there was no signifieant differenee between the two groups with respect to

the number of new perforators seen at one year DU (fig. 34). The number of new IPV

seen on DU increased with time following surgery and represents the progressive

nature of the disease..

■ ^ S E P S N SE PS

16

14

12

10No. o f new _

IP V ®64

2

0New at 1 wk New at 6wks New at 6m New at 1 yr

Follow -up

Figure 34 No. of New IPV seen during the follow-up period.

165

A note is made here in respect of errors which may have occurred with respect to

sonography of these subjects. Ideally the radiographer must have been blinded with

respect to the patients being scanned. Unfortunately in practice this was not possible

since even if the scar on the medial aspect of the calf was somehow covered up, the

SEPS clips are easily detectable on DU. With respect to inter and intra-observer

errors, no steps were taken to assess this however due to the randomised nature of the

trial and the predetermined protocols, conceptually all errors as a result of this should

occur equally in both groups. In an internal audit (not published), the radiographer

was able to detect 95% of all IPV as compared to operative findings. However the

lack of assessment of these errors does bring about a source of error which is not

accounted for.

The pain scores appear to be sensitive instruments as demonstrated by the pain scores

from the patient’s diary and the follow-up VAS for pain. The highest scores were

noted at the first post-operative day in the diaries with the mean of both groups being

39.2 (SEPSG range 0-80, NSEPSG 0-87, fig. 17). With in 14 days of the operation, the

pain scores had reduced to 12.9 in the SEPSG and 9.0 in the NSEPSG.

The highest score during the follow-up period was at one week (29.1 in SEPSG, 30.9

in the NSEPSG). The pain score subsided after that (fig 22, table 7) to 6.3 and 4.3

respectively at one year. These values are much lower than the pre-operative score

and represent a statistically significant improvement in the patient perception of pain

as a result of varicose veins.

There was good correlation between the available I week VAS for pain from the

patients diaries and I week follow-up appointment (SEPS 23.6/100 29.1/100,

Pearsons correlation = 0.626, p=0.03, NSEPSG 24.9/100 and 30.9/100, respectively

Pearsons correlation 0.66, P=0.01) even though the response rate of the 1 week

166

follow-up VAS was low (table 3). This adds more weight to the stability of the VAS

for pain.

The assessment of mobility of the patients followed much the same pattern as that for

pain, with the highest scores at Iwk post-operatively. The mobility scores for both

groups had improved at 1 year compared to the preoperative score (table 25).

The patient diaries also assessed the amount of pain relief tablets consumed and

assistance required during the 14 days following operation. The reduction in the

number of tablets taken in the NSEPS group was significant when compared to the

SEPS group. This is because the NSEPS group on average took a higher number of

tablets on the first operative day than the SEPS group, since both groups have an

average consumption of less than one tablet at 14 days.

The mean pre-operative VAS for the cosmetic appearances of the trial legs as

assessed by the subjects themselves were far higher than the scores for pain and

mobility in both groups. This gives a good insight into the perceived problem with

respect to patients with varicose veins. The cosmetic improvements at one year in

both groups were significant and there were no differences between the groups.

The patients in both groups had pre-operative scores in all dimensions of the SF-36

which were similar to the general population scores the only exception being that of

physical function score in the SEPSG (table 13). This goes some way to show the

generally good state of health of patients undergoing varicose vein surgery. It would

appear that our SEPS sample may have been slightly weighted towards people who

had a lower perception of their physical function. This is a chance occurrence since

the process of allocation was randomised.

Again as would be expected the SF-36 scores were lower (i.e. less well) at 1 week

compared to scores during the rest of the follow-up. The changes over one year are

167

shown in table 25. In neither group were these improvements significant, apart from

the score improvement for bodily pain in the SEPS group (P=0.002). Smith et a l, in

their study similarly found improvements in SF-36 scores at 6 weeks following

varicose vein surgery, which were only significant in mental health. The SF-36 is a

generic questionnaire, which may not be sensitive enough to appreciate the health

changes as a resulting from varicose vein surgery.

There were significant improvements in the Aberdeen questionnaire scores in each

group over the 12 month period (P <0.001Table 25). The only significant difference

between the two groups was observed at week one with the SEPSG mean score of

23.4 versus 18.2 in the NSEPSG (P<0.05). As would be expected the Aberdeen

Questionnaire is more sensitive to changes in symptoms brought about by varicose

vein surgery.

There were significant improvements in the RT90 times (90% of refilling time at

Photoplethysmography) in both groups at one year. There were no differences

between the groups with respect to the Photoplethysmography (PPG) times except at

one year with the NSEPSG having a higher RT90 time. However, the PPG times at

one year in the SEPSG, although lower than the NSEPSG, were well with in the

normal limits. Hence the significance of this difference appears not to be of clinical

importance. There was however a downward trend in the PPG times in the SEPSG

during the follow-up period and it would be interesting to observe the changes in

these values at 3 years and 5 years.

In 10 patients, from both groups, the RT 90 time was seen to have reduced at 1 year.

In 4 of these patients either the 1 year PPG were within normal limits or they had

reflux on DU whieh could account for the reduced RT90 times. The presence of

reflux in the remnant below knee Great Saphenous Vein (GSV) in 5 out of the

168

remaining 6 patients with markedly reduced and pathological PPG RT90 at 1 year,

was found not to be significant when compared to the 2 groups as a whole (5/6 vs.

39/63, Chi Square test P=0.076). Once again it must be noted that no attempt was

made to clarify inter and intra-observer errors which may have occurred in measuring

the PPG times.

In conclusion, the two groups were comparable samples with respect to

demographics, risk factors and classification of varicose veins. SEPS is effective in

the treatment of IPV and 80% of IPV can recur if they are not addressed at surgery.

The addition of SEPS to the HST&S does increase the total operating time by

approximately 16 minutes, and is not assoeiated with increased morbidity (pain,

mobility restriction, cosmetic effects). Further work is required to assess the strong

relationship between varicose veins and IPV. If a causative mechanism is elucidated

then perforator surgery should be part of routine treatment of varicose veins

169

FUTURE WORK AND QUESTIONS

Our study has shown that Incompetent Perforator Veins (IPV) recur following High

Saphenous Tie and Strip and multiple avulsions (HST&S) alone. IPV have already

been shown to be more commonly associated with recurrent varicose veins than

primary varicose veins (Rutherford et al 2001). Also IPV occur more commonly in

primary varicose veins than normal legs (Labropoulos et al. 1999). Whether this

represents a causation is largely unknown. We plan to add to the increase body of

evidence implicating IPV in recurrence and primary varicose veins, by rescanning the

patient groups at 3 years and 5 years. The patterns of reflux in the two groups at these

points, should shed further light on this subject. We will also assess whether clinical

recurrence has occurred and what each individual patient feels about the outcome of

their surgery.

The mechanism by which IPV affect the development of primary varicose veins is

still largely unknown. Although IPV are more commonly associated with varicose

veins, whether this is a primary event or re-entry secondary to underlying venous

hypertension is not known. Our attempt at trying to explain the mechanism of

pathological action of IPV were unfortunately unsuccessful on this occasion.

However this work is ongoing and will hopefully reach fruition.

We have shown that IPV remain open following HST&S of the GSV. We believe the

evidence of association of IPV with varicose veins is strong enough to merit pursue of

their surgical treatment. Also If reflux of venous blood is the mechanism through

which pathogenesis of varicose veins occurs, then all reflux disease must be overcome

(Kistner 1993). In order to achieve this goal, IPV must also be considered and treated.

Search for IPV should hence be considered routinely in the assessment of varicose

veins (during DU scanning) and the operation geared towards dealing with IPV as

170

well as the other more common areas of pathological reflux (e.g. SFJ). Subfascial

Endoscopic Perforator Surgery (SEPS) addresses the issue of surgical treatment of

IPVs convincingly, especially with the development of less invasive surgical

techniques becoming more and more important in the medical field since the latter

part of the 20* century. This process has been driven by the need to reduce the insult

of operations on the body and also patient demand for less invasive procedures and

more cosmetically acceptable scars. Varicose veins and IPV are no different in this

respect and developments in the fields are continuing (e.g. Radio-fi-equency ablation

(Fassiadis 2002, a&b). Laser therapy, foam sclerotherapy etc.). Further developments

are however on going in order to improve on the down falls of SEPS. This includes

the clips having come off the perforators and the 2 cm incision needed on the medial

aspect of the calf, which can be unsightly. As has been shown by this study the

patient’s perception of the cosmetic appearance of their legs scored highest in the pre­

operative VAS.

Trans-luminal occlusion of Perforators (TRLOP) has further developed minimal

invasive surgery in to “pin-hole surgery”. This technique has been developed at the

Whiteley clinic (Kianifard et al. 2002) and involves the introduction of a radio­

frequency catheter into the perforator vein via Seldinger technique (fig 35) and under

DU guidance. Once in position, the radio-frequency generator is activated and the

perforator vein is ablated and the complete destruction of the vein confirmed by DU

post procedure. This appears to be a successful and minimally invasive method of

dealing with IPV. However, randomised trials, further broad experience with this

technique and five year follow-up data are still outstanding to establish this as a

routine surgical tool surgical tool.

171

Figure 35 Seldinger teehnique used in the introduction of the TRLOP catheter

As a result of the development of TRLOP, Radio-Frequency Subfascial Endoscopic

Perforator Surgery (RFS) has developed. Specially designed radio-frequency catheters

are now being produced (Fig 36) which uses a similar technique to TRLOP to ablate

IPV.

Figure 36 RFS catheter

172

APPENDIX 1

Patient information sheet

Patient Information Sheet Varicose Veins and SEPS Operation

You have been diagnosed as suffering from varicose veins. This is caused by the valves within the veins themselves not working any more. Usually the valves in the veins cause the blood to flow from the foot back to the pelvis whenever you move, particularly when you walk. The effect of losing your valves is that the blood now gets pumped up your leg whenever you walk, but instead of moving on into the pelvis and back to the heart, it falls back down to the ankle.

This backward flow causes varicose veins in some people. In other people it causes itching at the ankle called venous eczema. If this gets worse it can go on to cause inflammation of the skin, discolouration of the skin and even ulceration.

The most effective treatment for varicose veins or veins in which the valves have stopped working is to remove the vein. Under a general anaesthetic, a cut is made in the groin. The vein that has lost its valves is then tied so that blood cannot flow into it. A wire is then passed down the vein and out through the skin lower down the leg. The vein is tied to this wire and then the wire is pulled out, a process called “stripping the vein”.

In some patients the valves in the veins which connect the deep and superficial veins in the leg, known as perforating veins, may also stop working. It is not known whether or not the treatment of these perforating veins by Subfascial Endoscopic Perforator vein Surgery (SEPS), at the time of the initial surgery will help to prevent your varicose veins recurring. SEPS involves making a small incision on the inside of the lower leg and using a telescope to look into the leg to find these veins. Clips are then put onto these veins and they are divided. This study is designed to allow us to assess whether the treatment of perforating veins with SEPS will help to prevent recurrence.

The allocation of patients to either group (operation with and without SEPS), is worked out at random. This ensures that no one knows which treatment you will receive before entering you into the trial.

The study will follow your progress for I year after your operation and will require you to attend for regular appointments at I week, 6 weeks, 6 months and I year. On each occasion you will have a number of painless tests performed:

The veins in your leg will be assessed by a Duplex ultrasound scan A photograph of your leg will be taken so that the cosmetic result can be assessed

173

Improvement in function will be measured using a Photoplethysmography machinewhich measures the time taken for blood to refill your legThere will be 2 short questionnaires about your health for you to completeYou will be asked to walk a distance of 50 metres whilst being watched and timed

These tests will also be performed before the operation so that we can assess any changes.

Your decision to participate in this study is entirely voluntary. Should you wish to participate in the trial you will be asked to sign a consent form. However at any stage you are free to withdraw from the trial and this will not affect your current or future treatment. With your permission, your GP will be notified of your entry into the trial.

Information about you and your treatment will be recorded and held on a computer database in accordance with the governing regulations. For verification of facts recorded as part of the trial we may need access to your hospital notes. Any information which is retrieved by this method will be subject to the same regulations as the trial data.

We would like to invite you to join this study. You will have the opportunity to discuss the procedure with one of the investigators, either Mr. Mark Whiteley, Consultant vascular surgeon, or Mr Babak Kianifard, research fellow in vascular surgery.

If you do not wish to be part of this study you will have the same surgery that has beenplanned, and will be seen again in clinic after six weeks.

If you do wish to contact either one of the investigators about any aspect of this study the contact numbers are below:

Mr. Mark Whiteley 01483571122 Ext. 4424 Mr Babak Kianifard 01483 571122 Ext. 4011

174

Consent form

Patient Consent Form

A randomised controlled trial investigating the role of Subfascial Endoscopic Perforator vein Surgery (SEPS) in the prevention of recurrence in primary varicose veins.

Name of Consultant enrolling the patient:

Patient's surname:

forename(s):

Date of Birth: / /

Gender: Male □ Female □

The patient should complete the remaining section of the form:(please circle the relevant answer to each question)

Have you read the patient information sheet? Yes No

Have you had the opportunity to ask questionsand discuss the study? Yes No

Have you received satisfactory answers toall your questions? Yes No

Have you received enough information about the study? Yes No

Who have you spoken to?(please write their name)

Do you understand that you are free to withdraw from the study at any time, without having to give a reason, without affecting your future medical care? Yes No

Do you give permission for your General Practitioner (GP)to be notified of your participation in this trial? Yes No

Do you agree to take part in the study? Yes No(if'yes' please sign below)

Signature:.................................................................................................

Nam e:.......................................................................................................

175

P r e - o p e r a t i v e p r o - f o r m a

(IN BLOCK CAPITALS)

Pro-forma Today's date:

SEPS RESEARCH PROJECT

PRIMARY SEPS □

LEFTD

NAME:Male n

ADDRESS:

□

RIGHTO

Female n

RECURRENCE □NO SEPSO BILATERALO

Age: D.O.B.:

PHONE NO.

SYMPTOMS & HISTORY:

DURATION:

Previous venous surgery (details including dates):

PM/SHX:

PREVIOUS DVT □ Details:

MEDICATION:

RISK FACTORS:

OCCUPATION:

Hours standing at work/normal day:1-2 hours □ 3-4 hours □ 5-6 hours □

NUMBER OF PREGNANCIES:

BMI: HEIGHT:

FAMILY HISTORY:

WEIGHT:

176

Pre-operative pro-formaCEAP CLASSIFICATION:

RClinicalNone □ □Telangiectases, reticular, □ □Mai. Rare □ □Varicose Veins □ □

Oedema (without skin changes) □ □Skin changes □ □Healed Ulcer □ □Active Ulcer □ □

AetiologyPrimary □ □Secondary □ □Congenital □ □If congenital on what basis:

AnatomicalSuperficial □ □Perforating □ □Deep □ □

PathophysiologicalReflux □ □Obstruction □ □Reflux + Obstruction □ □

CEAP Class

EXCLUSION CRITERIA:

Immobility □Previous DVT □Other:

177

Pre-operative pro-formaVisual Analogue Score Sheet

To help people say how they are feeling we have drawn a scale with the extreme feelings described at each end of the scale.

We would like you to indicate how you are feeling by drawing a cross in the appropriate position on the line.

PAIN

No Pain At All

The Most Severe Pain I’ve Ever Felt

MOBILITY

Full Mobility Without Restriction

I am Unable to Move At All

COSMETIC VIEW OF LEG

I am perfectly happy with the Cosmetic appearance of my Leg

My leg could not look worse than it does now

Visual Analogue Scores

Pain % Mobility____ % Cosmetic View %

178

Pre-operative pro-formaDuplex US

R LComp Reflux Not Seen Comp Reflux Not Seen

Sup

CFV □ □ □ □ □ □SFV □ □ □ □ □ □PopV □ □ □ □ □ □PTV □ □ □ □ □ □PER □ □ □ □ □ □Gastroc □ □ □ □ □ □L-S SystemSFJ □ □ □ □ □ □GSV(upper %) □ □ □ □ □ □GSV(mid %) □ □ □ □ □ □GSV(lower V2) □ □ □ □ □ □S-S SystemSPJ □ □ □ □ □ □SSV(upperl/3) □ □ □ □ □ □SSV(midl/3) □ □ □ □ □ □SSV(lowerl/3) □ □ □ □ □ □Post. Arch V □ □ □ □ □ □Giacomini □ □ □ □ □ □GSV-SSV CommV □ □ □ □ □ □Other veins only □ □

PerforatorsR L

How many? Not Seen How many? Not Seen

ThighCSVPost. Arch V □ □ □SSV □ □ □

Size From To Size1. mm mm2. mm mm3. ___mm mm4. mm mm5. mm mm6. mm mm

Size From To

179

Pre-operative pro-formaPHOTOPLETHYSMOGRAPHY

Refill Time sec

% Refill Tim e____sec

T90 sec

Photography

Cosmetic Score 1 2

Gait Observation

Normal □Mild Limp, Normal Speed □Moderate Limp, Normal Speed □Major Limp, Impaired Speed □Walking with 1 stick □Walking with other assistance □

Time to walk 30 metres: min sec

Quality of Life Questionnaires

SF-36 Score _

AQ Score _

180

P O S T - O P E R A T I V E D I A R Y

NAME Hospital No.: Date of Operation:

Please fill in the as instructed on a daily bases until 2 weeks post operatively.

POST-OPERATIVE DAY

PAE4

No Pain At All

The Most Severe Pain I’ve Ever Felt

MOBILITY

Full Mobility No Restriction

I am Unable to Move at All

(Doctors use only

Pain killers taken:

Name:

Pain % Mobility %)

Number:

Assistance required during the day: I.

2 .

3.

4.

5.

181

APPENDIX 2

S t u d y A p p r a i s a l Q u e s t i o n n a i r e

Study:

Type of study:

+1 -1

Clearly Stated Aim □ □

Justified size of sample (Power) □ □

Identified whether their measurements are valid and reliable □ □

Clearly stated their statistical methods □ □

Explained events (missing data, bias) □ □

Interpreted Their findings correctly (conclusions) □ □

Discussed interesting findings (outliers, comments) □ □

Reported comparison with the rest of the literature □ □

Clearly stated implications (are they relevant) □ □

182

Assessing Cohort studies

study:

Participants:

Relevant population under exam.?

Design:

Aims clearly stated?Is the design appropriate for the aim?How are they recruited? Correctly?Did it have a control group?Did it require one?Was the sample size justified?Was the intervention accurately measured? (reliability) Was the FU satisfactory?All data accounted for (Missing data?)Was the FU long enough for detection of imp. events? Were relevant outcomes ignored? (validity)

Results:

Are stats described?Do the numbers add up?Were basic data described?Was the statistical significance assessed?

The Findings:

Did any untoward events occur during the study?

What do the main findings mean? Explained?

Any other factors influenced the outcome?

Any important findings overlooked?

How are the null findings interpreted?

Are the results compared with others in the field?

What are the implications for your study?

+1 -1

□ □

□ □□ □□ □□ □□ □□ □□ □□ □□ □□ □□ □

□ □□ □□ □□ □

+1 -1

□ □

□ □

□ □

□ □

□ □

□ □

183

A s s e s s i n g C a s e C o n t r o l S t u d i e s

Study:

General: ±1____ A

How were cases obtained? Correctly? □ □Is the control group appropriate? □ □Were data collected in the same way in the 2 grps.? □ □

Design:

Are the aims clearly stated? □ □Is the method appropriate for the aim? □ □Was the size of the sample justified? □ □Valid? □ □Reliable? □ □

Analysis:

Are the stats Described? □ □Is it likely that an untoward event occurred? □ □Do the no. add up? □ □How was the data collected? Reliable? □ □

The Findings:

What do the main findings mean? Explained? □ □Has bias occurred? Where? □ □Is it possible confounding may have occurred? □ □How are the null findings interpreted? □ □Are important effects overlooked? □ □Are the results compared with others in the field? □ □

What are the implications for your study?

184

Assessing Clinical Trials

study:

General: + i_____^

Random allocation? □ □Correctly randomised? □ □Missing data? □ □Missing data Explained? □ □Was assessment blinded? □ □

Design:

Are aims clearly stated? □ □Was size justified? □ □Validity? □ □Reliability? □ □Could lack of blinding introduce bias? □ □

Results:

Are stats described? □ □Was stat signif. Assessed? □ □Were the basic data described? □ □Do the numbers add up? □ □Were treatment groups similar? □ □Treatment as per intention to treat? □ □Were the side effects recorded? □ □

The Findings:

What do the main findings mean? Explained? □ □Any other factors influenced the outcome? □ □Any important findings overlooked? □ □How are the null findings interpreted? □ □Are the results compared with others in the field? □ □What are the implications for your study?

185

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PAPERS, ABSTRACTS AND PRESENTATIONS

Papers

Kianifard B, Holdstock J, Allan C, Smith C, Price B, Whiteley MS. Perforator veins do not remained closed following long saphenous vein stripping - Results of a randomised trial with one year follow-up submitted Nov 2005

Kianifard B. Holdstock J, Whiteley MS. Radio-frequency ablation of varicose veins does not cause neo-vascularisation at the groin at one year - results of a case controlled study. In press 2005.

Kianifard B. Price S. Whiteley MS. Clipping perforators without dividing them could reduce postoperative pain and swelling following subfascial endoscopic perforator surgery. Annals of the Royal College of Surgeons of England. 84(3):210-1, 2002 May

Rutherford EE. Kianifard B. Cook SJ. Holdstock JM. Whiteley MS. Incompetent perforating veins are associated with recurrent varicose veins. [Journal Article] European Journal of Vascular & Endovascular Surgery. 21(5):458-60, 2001 May.

Abstracts and presentations:

Kianifard B, Holdstock J, Allan C, Smith C, Price B, Whiteley MS. Perforator veins do not remained closed following long saphenous vein stripping - Results of a randomised trial with one year follow-up. 2005 BJS 92(4):501-2

Kianifard B, Allan C, Holdstock, Whiteley MS. Perforator veins do not remain closed following long saphenous vein stripping - Preliminary results of a prospective randomised clinical trial. Br J Surg. 2003: 90; 491-509

Kianifard B, Holdstock J, Allan C, Smith C, Price B, Whiteley MS. Perforator veins do not remained closed following long saphenous vein stripping - Results of a randomised trial with one year follow-up. Accepted paper for meeting of the American College of Phlebology, San Francisco, Nov 2005

Kianifard B, Holdstock J, Allan C, Smith C, Price B, Whiteley MS. Perforator veins do not remained closed following long saphenous vein stripping - Results of a randomised trial with one year follow-up. Vascular Surgical Society, Harrogate, Nov. 2004 (Winner of the Venous Forum Prize).

Kianifard B, Holdstock J, Whiteley MS. Radio-frequency ablation of varicose veins does not cause neo-vascularisation at the groin at one year - results of a case controlled study. South West Thames Vascular Meeting. St.Georg’s Hospital, Feb 2004

Kianifard B, Allan C, Holdstock, Whiteley MS. Perforator veins do not remain closed following long saphenous vein stripping - Preliminary results of a prospective randomised clinical trial. Vascular Surgical Society of Great Britain & Ireland, Belfast, Nov. 2002.

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SYSTEMATIC REVIEW

Title: Subfacial endoscopic perforator surgery and duplex ultrasound.

Reviewer: Babak Kianifard

Date of most recent amendment: 17th August 2004

Components of Systematic review:

• Abstract

• Background

• Objectives and review questions

• Study selection criteria

• Search strategy including search terms and resources to be searched

• Study quality assessment checklists and procedures

• Data extraction strategy

• Description of the studies

• Results

• Conclusions

• Characteristics of included and excluded papers

• References included

206

Abstract

Objectives:

The aim of the review was to evaluate the effectiveness of Subfascial Endoscopic

Perforator Surgery (SEPS) in addition to conventional surgery (High Saphenous Tie

and Stripping (HST&S)) in the surgical treatment of primary non-ulcerated varicose

veins. A second search was made to look at the efficacy of ultrasound in the

assessment of incompetent perforating veins.

Search strategy:

A search was made using four major data bases, with the use of pre-defmed criteria.

Two separate searches were made, the first looking at the surgical procedure on the

affected population, the other concentrating on duplex ultrasound as the outcome

measure following surgery.

Selection criteria:

There is a lack of material with respect to the questions being asked. No randomised

control trials were found. All relevant papers other than case series were considered

and evaluated.

Data collection and analysis:

List of all papers were then scrutinised and irrelevant papers excluded. All other

papers were then studied and assessed separately using a simple study appraisal form

(appendix 2). Due to the small number of papers and the diverse methods of

assessment and populations studied within them, each paper which was included was

individually read and summarised.

207

Main results:

With respect to the intervention (SEPS) and the population involved (primary non­

ulcerated primary varicose veins), there were no suitable papers which tackled the

outcome following SEPS. With respect to the efficacy of ultrasound two papers were

of a high enough quality to be included.

Conclusions:

At present there is no correctly conducted study which looks at the use of SEPS in the

treatment of primary varicose veins.

Objectives and Review Questions

The aim of this review is to establish the level of evidence available to support or

disprove the efficacy of SEPS in conjunction with HST&S in improving the outcome

and recurrence of varicose veins.

Question: In patients undergoing surgery for primary non-ulcerated varicose veins, to

what extent is post-operative detected reflux altered by addition of SEPS.

Study Selection Criteria

Population Primary varicose veins

Intervention SEPS

Outcome Ultra sound detected reflux within 1 year

Study design Randomised control trial

208

Inclusion criteria:

Inclusion criteria

Population Primary non-ulceratedVaricose veins

Intervention Subfascial endoscopic perforatorSurgery

Outcome Duplex detected reflux

Study Design RCT, observational studies

Exclusion criteria

Recurrent, ulcerated varicose veins

Other procedures

Case report, expert opinion, technique papers, bench research.

Tvpe of narticinants and intervention

The group of patients interested in were those who were having their first operation

for CSV incompetence. This excludes all those patients with ulceration, recurrence,

SSV reflux and deep venous reflux.

The interested intervention carried out on these patients is SEPS. This may be carried

out in conjunction with the accepted treatment for GSV reflux, HST&S. All other

interventions were disregarded.

Tvpes of outcome measures

The outcome measure was reflux as detected by duplex ultrasound (DU). A separate

review was carried out with respect to the efficacy of duplex ultrasound with this

respect.

209

Types o f papers

Following the search strategy on the different search engines, all the lists were

collated and scanned. All those papers which appeared unrelated were discounted at

this point. All other papers were read individually and assessed by using a study

appraisal questionnaire.

A search was made to include all papers relevant to surgery for primary non-ulcerated

varicose veins. There were no randomised control trials related to the type of surgery

involved. All papers observational papers (cohort, case-control studies, cross-

sectional studies, before and after studies and case series) were considered for

appraisal. All papers concerned with case reports, bench research and expert opinions

were disregarded.

Search Strategy Including Search Terms and Resources to be SearchedSearch:

Electronic Databases:

National Research Register

CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to present)

EMBASE (1974 to present)

MEDLINE (1951 to present)

Cochrane library (Central Register of Controlled Trials (CENTRAL), Database of

Systematic Reviews, Database of Abstracts of Reviews of Effects, Database of

Methodology Reviews, Methodology Register(CMR), Health technology assessment

database (HTA), NHS Economic evaluation database (NHS EED)

210

Search Term

The terms used are outlined in the table 24 (Intervention and population) and 2 (DU)

below. Each citation was studied and excluded if not relevant. All remaining papers

were then read fully and appraised.

211

Table 23 MEDLINE (population and Intervention) search criteria.

Info addedNo. Database Search term Info added since Results

Medline- 1951 to

1 date (VARICOSE AD J VEINS).MJ. Unrestricted 7182Medline-1951 to

2 date (VENOUS ADJ INSUFFICIENCY).MJ. unrestricted 2473Medline-1951 to

3 date VENOUS ADJ REFLUX unrestricted 438Medline-1951 to

4 date PERFORATOR ADJ VEINS unrestricted 96Medline-1951 to

5 date 1 OR 2 OR 3 OR 4 unrestricted 9586Medline- unrestricted1951 to SUBFASCIAL ADJ ENDOSCOPIC

6 date ADJ PERFORATOR ADJ SURGERY 38Medline- ENDOSCOPY.W..MJ. AND unrestricted1951 to VASCULAR-SURGICAL-

7 date PROCEDURES.MJ. 87Medline- unrestricted1951 to

8 date SEPS I 7 4 5

Medline- unrestricted1951 to PERFORATOR ADJ VEIN ADJ

9 date SURGERY 20Medline- unrestrictedI95I to

10 date 6 OR 7 OR 8 OR 9 1836Medline- unrestricted1951 to

11 date 5 AND 10 72Medline- unrestricted1951 to

12 date DEEP OR ULCER 175304Medline-1951 to

13 date 11 NOT 12 unrestricted 17

212

Table 24 EMBASE (Duplex ultrasound) search criteria

No. Database Search term

EMBASE - 1974 to date

EMBASE - 1974 to date

EMBASE - 1974 to date

EMBASE - 1974 to date

duplex ADJ ultrasound

colour ADJ duplex

colour ADJ duplex

1 0 R 2 0R 3

10

EMBASE -1974 to date varicose ADJ veins

EMBASE -1974 to date venous ADJ reflux

EMBASE -1974 to date 6 OR 7

EMBASE -1974 to date 8 AND 5

EMBASE -1974 to date deep OR ulcer

EMBASE -1974 to date 9 NOT 10

Info added Since unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

unrestricted

Results

1268

706

706

1852

2413

605

2888

131

136567

56

213

Study Quality Assessment Checklists and Procedures

After discarding all non relevant paper, each paper was read and scored using the

appraisal questionnaire. Those that scored 50% were summarised and included in this

review. All other papers were discarded.

214

Data Extraction Strategy

Due to the lack of suitable papers, the studies selected were summarised individually.

Description of the Studies

Antoch-G, Pourhassan-S, Hansen-0, Stock-W2002 Comparison o f colour Doppler ultrasonography, ascending phlebography and clinical examination in the diagnosis o f incompetent calf perforating veins. Br J Surg 89:192-3

The main objective of this paper was to compare the ability of ultrasound, ascending phlebography and clinical examination in defining perforator vein incompetence. Patient and MethodsSixty three legs in 50 patients were entered into the study. This appears to be large enough number for this comparison study, however no reason or explanation given for this number of patients. Also the exact source and recruitment process is not described. Since all patients included were classified in the same class of chronic venous insufficiency, they do make a good comparison group.No time period given for the duration of study and date, however the paper was published in 2001 and is up to date.All participants were examined, had ascending phlebography and colour duplex ultrasound. This was followed by confirmation of these findings at surgery (SEPS), carried out by surgeons who were blinded to previous investigations. However although enough information is given about assessment of IPV during SEPS, there is not enough information with regards to the assessors themselves and their experience with SEPS.McNemara’s test was used to analyse differences in values of specificity and sensitivity for matched pair proportions. This is an appropriate test for comparing proportions.ResultsUltrasound is significantly more sensitive (mean 80%) than ascending phlebography (66%) in assessing IPV. Clinical examination was also more sensitive (79%) than ascending phlebography. There was no significant difference between ultrasound and ascending phlebography with respect to specificity. Sensitivity was improved to 87% by combining clinical examination and colour duplex ultrasound.No withdrawals mentioned.No morbidity or complications mentioned.Discussion.Ultra sound is superior to ascending phlebography in imaging cockett perforators, and the addition of phlebography has no further advantage over ultrasound and clinical examination.Comparisons were made with two other similar papers and similarities and differences discussed.Use of ascending phlebography should be limited to patients for whom ultrasound is not available or where its results are questionable.

215

Phillips-G-W-L, Paige-J, Molan-M-P 1995 A comparison o f colour duplex ultrasound with venography and varicography in the assessment o f varicose veins. Clinical Radiol 50(l):20-25

The aim is to prospectively compare Ultrasound (US) findings and compare them against the more established ascending plus varicography (V), in patients with varicose veins.Patients and Methods.Over a 9 month period, 68 (93 legs) consecutive patients referred for pre-operative assessment of varicose veins, were recruited. Forty nine of the 93 legs represented recurrent varicose veins.A full description of the three techniques is given along with the fact that US and V-V were performed by two different investigators who were blinded with regards to the other investigation.The findings were confirmed at surgery. However this was based on the finding of the investigations (US and V). The false negative rate also can not be assessed by surgery. A big assumption by the authors is that the total number of abnormal communications seen by V or US to represent 100% of the abnormalities present.Nine cases did not proceed to surgery due to deep venous incompetence.The remaining 84 underwent the appropriate interventions.ResultsNo false positive cases identified. Incompetent calf perforators were present in 62 legs (74%).V and ultrasound had high detection rates for sapheno-femoral and sapheno-popliteal junction disease with 90% being demonstrated by either technique. Varicography was found to be superior in assessment of incompetent calf perforators with 83% being demonstrated by V and 60% by US.DiscussionComparison is made with different papers.Accuracy of US in identifying IPV is significantly less than that of V. However 10% of IPV missed on V were seen on US.Suggest that US alone is second best, and all patients should have all three modalities of investigation before surgery.The authors do mention that all 9 cases with post-thrombotic changes which prohibited surgery, were diagnosed by ascending venography and 2 of these were missed by US. Also another 2 cases which appeared normal on venography were abnormal on US. This does raise the question of the accuracy of the investigator carrying out the US or the accuracy of machine being used. Ultra sound is now the accepted standard for diagnosis of post-thrombotic changes seen within the deep veins. This study is more than 10 years old and the efficacy of modem machines have advanced greatly over this period. This questions the relevance to the current situation.

Results

Despite an extensive search of literature no adequate studies exist that investigate the place of SEPS in the treatment of primary non-ulcerated varicose veins. However searching through the different studies, SEPS is being carried out in a large number of international institutions.

216

With respect to ultrasound, the most up to date paper reviewed showed duplex ultrasound to be superior to phlebography in assessing perforator veins. The other paper reviewed however disputes this. The later paper however is most probably out of date now, due to the progression of accuracy of ultrasound since publication of this paper (ten years ago).

Conclusions

There is insufficient evidence at present to assess the place of SEPS in the treatment of primary varicose veins.Ultrasound appears to be an accurate form of investigation of IPV.As the background to this thesis outlines, the place of perforator surgery in the treatment of primary non ulcerated patients suffering with varicose veins has not been established. There are presently no published randomised trials which have assessed the impact of SEPS on the treatment of such patients, and the long term fate of perforators in treated varicose veins is still unknown. Our aim was to assess the effect of SEPS, as part of randomised clinical trial, and to observe the fate of IPV with in one year following surgery aimed directly at the perforators (Subfascial endoscpic perforator surgery group, SEPSG) as compared to HST&S alone (Non SEPS Group, NSEPSG). DU was used to assess all patients and the primary outcome measure was the incidence of pathological venous reflux and IPV within a one year period. As part of secondary outcome measure PPG, quality of life questionnaires, visual analogue scores, surgical data and post-operative patient diaries were used to observe any appreciable differences in the two groups and to document the additional effect of SEPS on the patient’s recovery.In conjunction with the above, we had hoped to directly assess the contribution of IPV to venous hypertension in chronic venous disease. It was hoped that by direct cannulation of the perforator veins and observation of calibrated pressure changes adjacent to both incompetent and competent perforator veins, an idea of the contribution of IPV to venous hypertension may be surmised. However, in practice this technique did not prove to be fruitful due to the difficulties in instrumentation and limited reproducibility of the technique.

Characteristics o f Included and Excluded Papers

Excluded papers:Population and intervention

Alukhanian-O-A, Martirosian-Kh-G, Aristov-D-S, Sviatenko-I-V. 2003 The role o f endoscopic ligation o f the perforating veins in the treatment o f chronic venous insufficiency under conditions of the one- day surgery center Angiologiëiîa i sosudistaëiîa khirurgiëiia VOL: 9 (2), P: 62-5 Day surgery and Chronic venous insufficiency

Rulli-Francesco 2003 Regarding "Subfascial endoscopic perforator vein surgery combined with saphenous vein ablation: results and critical analysis". J-Vasc-Surg38 (5): 1139 Other procedures

Pai-Paresh-R, Bhandarkar-Deepraj-S. 2003 Modified balloon dissector in subfascial endoscopic perforator surgery. European journal o f vascular and endovascular surgery 26 (1), P: 105-6 Technique

217

Kianifard-B, Price-S, Whiteley-M-S 2002 Clipping perforators without dividing them could reduce postoperative pain and swelling following subfascial endoscopic perforator surgery Annals o f the Royal College of Surgeons of England 84 (3): 210-1 . Technique

Lee-D-W, Chan-A-C, Lam-Y-H, Wong-S-K, Ng-E-K, Law-B-K, Chung-S-C 2001 Subfascial endoscopic perforator vein surgery (SEPS) using the ultrasonic scalpel. Surgical endoscopy 15 (12):1491-3 Techniques paper

Irace-L, Faccenna-F, Gossetti-B, Brunetti-M, Tozzi-M, Jabbour-J, Faraglia-V.2002 Indications and short term results o f subfascial endoscopic perforator surgery (SEPS). Minerva cardioangiologica 50 (1): 21-7 Leg ulceration.

Scavée-V, Theys-S, Schoevaerdts-J-C. 2001 Transilluminated powered mini-phlebectomy: early clinical experience. Acta chirurgica Belgica 101 (5): 247-9 Phlebectomy

Hirokawa-M, Oda-K, Yamamoto-A, Sasaguri-S. 2001 A soft dual-port trocar for endoscopic subcutaneous surgery. Surgical endoscopy 15 (5): 520-3 Surgical instrument

Meyer-T, Cavallaro-A, Lang-W. 2000 Duplex ultrasonography in the diagnosis o f incompetent Cockettveins. European journal of ultrasound 11 (3): 175-80Imaging

DePalma-R-G. Perforator incompetence.2000 Case o f perforator incompetence—making SEPS better. Hawaii medical journal 59 (6): 256-8 Case study

Krohg-Sorensen-K. 2003 Treatment o f venous insufficiency. Tidsskrift for den Norske Laegeforening 123 (17):2433-2434 Treatment o f venous insufficiency

Sam-R-C, Silverman-S-H, Bradbury-A-W. 2004 Nerve injuries and varicose vein surgery. European Journal o f Vascular and Endovascular Surgery 27(2): 113-120 Nerve injury

Costante-F, Panero-D, Lanati-1, Giordano-0. 2003 Subfascial endoscopic perforating surgery. Personal experience. Minerva Chirurgica 58: 557-562 Personal experience

Hirokawa-M, Inoue-Y, Iwai-T. 2003 Subfascial endoscopic perforator surgery using a soft trocar for varicose veins in the lower leg. Phlebology 18(1): 30-34 Instrument paper

Haruta-N, Asahara-T, Marubayashi-S, Sugino-K, Miura-Y, Nakahara-H.2002 Technical procedure of two-port system subfascial endoscopic perforator vein surgery (TPS-SEPS). International Journal o f Angiology ll(l):17 -22 Technique

Lee-D-W-H, Chan-A-C-W, Lam-Y-H, Wong-S-K-H, Ng-E-K-W, Law-B-K-B, Chung-S-C-S. 2001 Subfascial endoscopic perforator vein surgery (SEPS) using the ultrasonic scalpel. Surgical Endoscopy 15(12):1491-1493 Instrument

Rulli-F, Tucci-G-F, Grande-M, Muzi-M-G, Farinon-A-M. 2001 Development o f a model for training and evaluation in subfascial endoscopic perforator surgery (SEPS). Minimally Invasive Therapy and Allied Technologie 10:239-242 Model for evaluation of SEPS

Bohler-Sommeregger-K. Experience with Subfacial endoscopic perforans surgery.Vasomed 13:112-114 Personal experience

218

Hirokawa-M, Oda-K, Yamamoto-A, Sasaguri-S. 2001 A soft dual-port trocar for endoscopicsubcutaneous surgery. Surgical Endoscopy 15: 520-523Instrument

Meister-R, Schmidt-0, Lang-W. 2000 SEPS in post-thrombotic syndrome or in varicose syndrome - Is there a consent between two different indications? Phlebologie 29:54-57 Post-thrombotic limbs

Meyer-T, Cavallaro-A, Lang-W. 2000 Duplex ultrasonography in the diagnosis o f incompetent Cockett veins. European Journal o f Ultrasound 11:175-180 Duplex in dx of cocketts

Lin-S-D, Tsai-C-C, Lin-T-M, Lee-S-S, Chang-K-P, Lai-C-S. 2000 Endoscope-assisted correction of primary varicose veins. Annals of Plastic Surgery 44:241-249, ISSN: 0148-7043. Technique

Duff-C-A, Fischer-R-H, Linde-N. 1999 External retraction technique (ERT) improves subfascial spacein endoscopic perforator vein surgery. Phlebologie 28:132-134Technique

Duff-C-A, Fischer-R-H, Linde-N. 1999 Creation of optimal Subfacial space in endoscopic perforator vein surgery with external retraction technique (ERT) Vasomed 11:148-152 Technique

Perrin-M. 1999 Venous leg perforating veins. Journal des Maladies Vasculaires 24:19-24 Review article.

Fischer-R, Schwahn-Schreiber-C, Sattler-G, Bergan-J-J. 1998Consensus paper Conclusions of a consensus conference on subfascial endoscopy o f perforating veins in the medial lower leg. Vascular Surgery 32:339-347

Whiteley-M-S, Smith-J-J, Galland-R-B. 1998 Subfascial endoscopic perforator vein surgery (SEPS): Current practice among British surgeons. Annals o f the Royal College o f Surgeons o f England 80:104- 107 Questionnaire paper.

Whiteley-M-S, Smith-J-J, Galland-R-B. 1997 Tibial nerve damage during subfascial endoscopic perforator vein surgery. British Journal o f Surgery 84:51 Case report.

Fischer-R, Sattler-G, Vanderpuye-R. 1993 Endoscopic treatment of incompetent perforator veins. Present state. Vasa - Journal o f Vascular Diseases 22:3-7 Out o f date.

Endoscopic versus open subfascial division of incompetent perforating veins in the treatment o f venous leg ulceration: a randomized trial. J Vase Surg 1997;26(6):1049-54 ulceration

Comparison between the CHIVA cure and stripping in the treatment o f varicose veins o f the legs: follow-up o f 3 years. Journal des Maladies Vasculaires, 1996;21(l):40-46 Stripping technique comparison

Excluded papers:

Duplex ultrasound

Gervaziev-V-B, Kolobova-O-I. 2003 Some features o f orthostatic venous haemodynamics o f the lower extremities in healthy, subjects and patients with varicose disease according to duplex scanning data. Angiologiëiîa i sosudistaëiîa khirurgîëiîa 9: 47-52 Haemodynamics

Safar-Hussein, Shawa-Naèl, Al-Ali-Jasem, Al-Nassar-Mohammad, Dashti-Hussein, Asfar-Sami. 2004 Is there a need for Doppler vascular examination for the diagnosis o f varicose vein? A prospective study. Medical principles and practice 13: 43-6 Doppler

219

Pichot-Olivier, Kabnick-Lowell-S, Creton-Denis, Merchant-Robert-F, Schuller-Petroviae-Sanja, Chandler-James-G. 2004 Duplex ultrasound scan findings two years after great saphenous vein radiofrequency endovenous obliteration. Journal of vascular surgery 39: 189-95 Different technique.

Nobel-W, Janka-H-U. 2003 Differential pain and swelling o f the lower leg diagnosis with colour-coded duplex ultrasound. Schweizerische Rundschau fèur Medizin Praxis 92: 1133-5 Leg pain

Prave-F, Hach-Wunderle-V, Hach-W. 2003 Vascular manifestation of von Recklinghausenneurofibromatosis : case report o f venous dysplasia. VASA 32:36-9Neurofibromatosis

Rautio-T, Perala-J, Biancari-F, Wiik-H, Ohtonen-P, Haukipuro-K, Juvonen-T. 2002 Accuracy o f hand­held Doppler in planning the operation for primary varicose veins. European journal o f vascular and endovascular surgery 24:450-5 Hand held Doppler.

Barakat-Maha. 2002 Doppler sonographic findings in children with idiopathic portal vein cavernous deformity and variceal haemorrhage. Journal o f ultrasound in medicine 21: 825-30 Hand held Doppler

Barbuscia-M, Crocco-P, Sano-M, Di-Pietro-R, Melita-G, Rizzo-A-G, Di-Pietro-N, Gorgone-S. 2002 Colour-Doppler sonographic mapping for the choice o f treatment in variceal disease. II Giomale di chirurgia 23:104-9 Variceal disease.

Smith-J-J, Brown-L, Greenhalgh-R-M, Davies-A-H.2002 Randomised trial of pre-operative colour duplex marking in primary varicose vein surgery: outcome is not improved. European journal of vascular and endovascular surgery 23: 336-43 technique

Campbell-B 2001 Hand held Clinical and hand-held Doppler examination of primary varicose veins. Annals of the Royal College o f Surgeons of England 83:287-8 Doppler

Vin-F, Chleir-F. 2001 Ultrasonography of postoperatively recurrent varicose veins in the area o f the short saphenous vein. Annales de chirurgie 6: 320-4 Small saphenous vein.

Olapade-Olaopa-E-0, Dikko-B-U, Foy-D-M, Darke-S-G. 2000 The selective use of duplex scanning in the pre-operative assessment o f primary and uncomplicated varicose veins identifies patients with 'early' morphological disease. African journal of medicine and medical sciences 29:35-9 Preo- operative scan.

Vrouenraets-B-C, Keeman-J-N. 2001 Physical diagnostics-duplex scanning is necessary only for selected patients with varicose veins. Nederlands tijdschrift voor geneeskunde 145:774-8 Selective duplex scaning.

Widmer-M-K, Schmidli-J, Carrel-T. 2001 Minimally invasive therapy in varicose veins. Schweizerische Rundschau fèur Medizin Praxis 90:205-12 Tutorial

Kroger-K, Massalha-K, Rudofsky-G. 2000 Colour Doppler sonography of arteries associated with perforating veins. International angiology 19:228-30 Arterial

Pichot-0, Sessa-C, Chandler-J-G, Nuta-M, Perrin-M. 2000 Role o f duplex imaging in endovenous obliteration for primary venous insufficiency. Journal o f endovascular therapy 7:451-9 Endovascular.

Boivin-P, Cornu-Thenard-A, Charpak-Y. 2000 Pregnancy-induced changes in lower extremity superficial veins: an ultrasound scan study. Journal o f vascular surgery 32:570-4 pregnancy

Kahle-B, Hummel-S, Deichmann-M, Petzoldt-D. 2000 Determining the severity o f venous insufficiency with duplex sonography. Der Hautarzt; Zeitschrift fèur Dermatologie, Venerologie, und verwandte Gebiete 51: 70-4 Severity on duplex

220

Sandri-J-L, Barros-F-S, Pontes-S, Jacques-C, Sailes-Cunha-S-X. 1999 Diameter-reflux relationship in perforating veins o f patients with varicose veins. Journal of vascular surgery 30:867-74 Diameter reflux relationship

Chow-L, Jeffrey-R-B-Jr. 1999 Intramural varices o f the bile duct: an unusual pattern o f cavernous transformation o f the portal vein. American journal o f roentgenology 17 :1255-6 Bile duct.

Valentin-L-I, Valentin-W-H. 1999 Comparative study o f different venous reflux duplex quantitation parameters. Angiology 50:721-8 Quantitative parameters.

6Labropoulos-N, Kang-S-S, Mansour-M-A, Giannoukas-A-D, Buckman-J, Baker-W-H. 1999 Primary superficial vein reflux with competent saphenous trunk. European journal o f vascular and endovascular surgery 18:201- GSV reflux

Jiang-P, van-Rij-A-M, Christie-R, Hill-G, Solomon-C, Thomson-I. 1999 Recurrent varicose veins: patterns o f reflux and clinical severity. Cardiovascular surgery 7:332-9

Goktay-A-Y, D icle-0, Yagci-B. Asymptomatic ureteral varices: detection by Doppler sonography. 1999 Journal o f clinical ultrasound 27:353-5 Ureteral varices

Broek-T-A. 1999 Preoperative duplex imaging is required before all operations for primary varicose veins. The British journal o f surgery 86:570 Pre-operative duplex.

Vrouenraets-B-C, Keeman-J-N. 1999 Preoperative duplex imaging is required before all operations for primary varicose veins.The British journal o f surgery 86:570 Pre-operative duplex.

Khaira-H-S, Jewkes-A, Jones-B. 1999 Preoperative duplex imaging is required before all operations for primary varicose veins. The British journal o f surgery 86:569-70 Pre-operative duplex.

Meyer-F-J, Taylor-P-R, Bumand-K-G. 1999 Preoperative duplex imaging is required before all operations for primary varicose veins. The British journal o f surgery 86:569 Pre-operative duplex.

Darke-S-G. 1999 Preoperative duplex imaging is required before all operations for primary varicose veins. The British journal o f surgery 86:569 Pre-operative duplex.

Kent-P-J, Weston-M-J. 1998 Duplex scanning may be used selectively in patients with primary varicose veins. Annals o f the Royal College of Surgeons o f England 80:388-93 Elective use of duplex.

Okuda-K, Matsutani-S, Takayasu-K. 1999 Images o f Interest. Hepatobiliary and pancreatic: an alcoholic man with a lesion in the splenic hilum. Journal of gastroenterology and hepatology 14:197 Hepatobiliary.

Pfyffer-M. 1998 Preoperative assessment o f primary varicose veins. Schweizerische medizinische Wochenschrift 128:1772-80 Pre-operative duplex.

Di-Nardo-E, Colamussi-G, Pitrelli-N, Lepore-R, Bongarzoni-G. 1998 Classification o f varices with Doppler ultrasonography mapping. Clinical and hemodynamic correlation. Minerva chirurgica 53:615- 8 Classification o f varicose veins.

Benabou-J-E, Molnar-L-J, Cerri-G-G. 1998 Duplex sonographic evaluation o f the sapheno-femoral venous junction in patients with recurrent varicose veins after surgical treatment. Journal o f clinical ultrasound 26: 401-4 Patterns o f reflux.

Evans-C-J, Allan-P-L, Lee-A-J, Bradbury-A-W, Ruckley-C-V, Fowkes-F-G. 1998 Prevalence of venous reflux in the general population on duplex scanning: the Edinburgh vein study. Journal of vascular surgery 28:767-76 Prevalence.

221

Barzilai-M, Lemer-A, Rivlin-J. 1998 Adhesion-related abdominal wall varices: demonstration by colour Doppler sonography. American journal o f roentgenology 170:1670 Abdominal wall varices.

Georgiev-M 1998. The preoperative duplex examination. Dermatologie surgery 24:433-40 Pre­operative duplex.

Pardy-B-J. 1998 Hand-held Doppler as a screening test in primary varicose veins. The British journal o f surgery 85 : 424 Hand held Doppler.

Abu-Own-A, Coleridge-Smith-P-D. 1998 Hand-held Doppler as a screening test in primary varicose veins. The British journal o f surgery 85:424 Hand held Doppler.

Baud-J-M, Lemasle-P. 1997 Current studies useful for indications in the treatment o f varicose veins of the lower limbs. Preoperative explorations. Annales de chirurgie 51:729-34. Indications for treatment.

Komatsuda-T, Ishida-H, Konno-K, Hamashima-Y, Ohnami-Y, Naganuma-H, Asanuma-Y, Masamune- 0.1998 Colour Doppler findings of gastrointestinal varices. 1998 Abdominal imaging 23:45-50 Gastrointestinal.

Franco-G. 1997 Ultrasonographic exploration for recurrent varicose veins in the popliteal fossa after surgery. Journal des maladies vasculaires 22:336-42 Popliteal fossa.

Darke-S-G, Vetrivel-S, Foy-D-M, Smith-S, Baker-S. 1997 A comparison o f duplex scanning and continuous wave Doppler in the assessment o f primary and uncomplicated varicose veins. European journal o f vascular and endovascular surgery 14:457-61 Comparison of duplex and cw ultrasound.

Komatsuda-T, Ishida-H, Konno-K, Hamashima-Y. 1998 Asymptomatic small-bowel varices. American journal of roentgenology 170:513-4 Bowel varices

Campbell-W-B, Niblett-P-G, Ridler-B-M, Peters-A-S, Thompson-J-F. 1997 Hand-held Doppler as a screening test in primary varicose veins. The British journal of surgery 84:1541-3 Hand held Doppler.

Kawaguchi-S, Nakase-H, Noguchi-H, Yonezawa-T, Morimoto-T, Sakaki-T.1997 Orbital varix diagnosed by colour Doppler flow imaging—case report. Neurologia medico-chirurgica 37:616-9 Orbital varices.

Gabata-T, M atsui-0, Kadoya-M, Yoshikawa-J, Ueda-K, Nobata-K, Kawamori-Y, Takashima-T. 1997 Gallbladder varices: demonstration o f direct communication to intrahepatic portal veins by colour doppler sonography and CT during arterial portography. Abdominal imaging 22:82-4 Gallbladder varices.

Fiechtner-H Riither-U Ulshofer-T Sessler-R, Nunnensiek-C, Rassweiler-J, Jipp-P. 1996 Colour-coded Doppler sonography in the diagnosis o f abdominal masses. Urologia internationalis 56:184-7 Abdominal masses.

Dixon-P-M. 1996 Duplex ultrasound in the pre-operative assessment o f varicose veins. Australasian radiology 40:416-21. Pre-operative duplex.

Pardo-J, Rabinerson-D, Szendro-G, Kaplan-B. 1996 A different option for transvaginal colour Doppler imaging: the diagnosis o f pelvic varicosities. Ultrasound in obstetrics & gynecology 8:137-8 Trans- vaginal.

Pleass-H-C, Holdsworth-J-D. 1996 Audit o f introduction of hand-held Doppler and duplex ultrasound in the management of varicose veins. Annals o f the Royal College of Surgeons o f England 78:494-6 Hand held Doppler.

Campbell-W-B, Halim-A-S, Aertssen-A, Ridler-B-M, Thompson-J-F, Niblett-P-G.1996 The place o f duplex scanning for varicose veins and common venous problems. Annals o f the Royal College o f Surgeons of England 78:490-3 Venous problems

222

Erden-A, Ozcan-H, Aytaç-S, Sanlidilek-U, Cumhur-T. 1996 Intrarenal varices in portal hypertension: demonstration by colour Doppler imaging. Abdominal imaging 21:549-50 Intrarenal.

Tong-Y, Royle-J. 1996 Recurrent varicose veins after short saphenous vein surgery: a duplex ultrasound study. Cardiovascular surgery 4:364-7 Short saphenous vein.

Guth-E, Katz-M-D, Hanks-S-E, Teitelbaum-G-P, Ralls-P, Korula-J. 1996 Recurrent bleeding from ileal varices treated by transjugular intrahepatic portosystemic shunt: value o f Doppler ultrasonography in diagnosis and follow-up. Journal o f ultrasound in medicine 15:67-9 Bleeding varices.

Baldt-M-M Bohler-K, Zontsich-T, Bankier-A-A, Breitenseher-M, Schneider-B. 1996 Preoperative imaging o f lower extremity varicose veins: colour coded duplex sonography or venography. Journal o f ultrasound in medicine 15:143-54 Mostbeck-G-H. Pre-operative duplex.

Evers-E-J, Wuppermann-T. 1995 Ultrasound diagnosis in post-thrombotic syndrome. Comparative study with colour duplex, cw-Doppler and B-image ultrasound. Ultraschall in der Medizin 16:259-63 Post-thrombotic limbs.

Fischer-G, Sackmann-M. 1995 Value o f endoscopic colour Doppler ultrasound in the diagnosis of gastric varices and follow-up o f therapeutic cyanoacrylate obliteration. Zeitschrift fèur Gastroenterologie 33:727-8 Endoscopic.

Vallance-S. 1995 Application of Doppler/ultrasound examination for varicose veins in a provincial hospital. The Australian and New Zealand journal o f surgery 65:787-92 All scans.

Kanter-A, Gardner-M, Isaacs-M. 1995 Identification o f arteriovenous anastomoses by duplex ultrasound. Implications for the treatment o f varicose veins. Dermatologie surgery 21: 885-9 Arterio­venous anastamosis.

Myers-K-A, Ziegenbein-R-W, Zeng-G-H, Matthews-P-G. 1995 Duplex ultrasonography scanning for chronic venous disease: patterns of venous reflux. Journal of vascular surgery 21:605-12 Patterns of reflux.

Kostas-T, loannou-C-V, Touloupakis-E, Daskalaki-E, Giannoukas-A-D, Tsetis-D, Katsamouris-A-N. 2004 Recurrent varicose veins after surgery: A new appraisal of a common and complex problem in vascular surgery. European Journal o f Vascular and Endovascular Surgery 27:275-282 Recurrent varicose veins.

Pichot-0, Kabnick-L-S, Creton-D, Merchant-R-F, Schuller-Petroviae-S, Chandler-J-G. 2004 Duplex ultrasound scan findings two years after great saphenous vein radiofrequency endovenous obliteration. 2004 Journal o f Vascular Surgery 39:189-195 Different technique

Mendoza-E, Caggiati-A. 2003 The anatomical bases of ultrasound diagnosis and surgical treatment for varicose veins. Gefasschirurgie 8:295-303 Anatomy

Garner-J-P, Heppell-P-S-J, Leopold-P-W. 2003 The lateral accessory saphenous vein - A common cause o f recurrent varicose vein. Annals o f the Royal College o f Surgeons o f England 85:389-392. Common cause o f recurrence.

Lane-R-J, Graiche-J-A, Coroneos-J-C, Cuzzilla-M-L. 2003 Long-term comparison o f external valvular stenting and stripping of varicose veins. ANZ Journal o f Surgery 73:605-609 Valvular stenting

Danielsson-G, Norgren-L, Jungbeck-C, Peterson-K. 2003 Global venous function correlates better than duplex derived reflux to clinical class in the evaluation of chronic venous disease. International Angiology 22:177-181 Venous function.

Zan-S, Varetto-G, Maselli-M, Scovazzi-P, Moniaci-D, Lazzaro-D. 2003 Recurrent varices after internal saphenectomy: Physiopathological hypothesis and clinical approach. MinervaCardioangiologica 51:79-86 Saphenectomy

223

Yamamoto-N, Unno-N, Mitsuoka-H, Saito-T, Miki-K, Ishimaru-K, Kaneko-H, Nakamura-S. 2002 Preoperative and intraoperative evaluation of diameter-reflux relationship of calf perforating veins in patients with primary varicose vein. Journal o f Vascular Surgery 36:1225-1230 Diameter o f IPV.

Fassiadis-N, Kianifard-B, Holdstock-J-M, Whiteley-M-S. 2002 A novel approach to the treatment o f recurrent varicose veins. International Angiology 21:275-276 New technique.

Danielsson-G, Eklof-B, Grandinetti-A, Kistner-R-L. 2002 The influence o f obesity on chronic venous disease. Vascular and Endovascular Surgery 36:271-276 Obesity.

Chang-C-J, Chua-J-J. 2002 Endovenous laser photocoagulation (EVLP) for varicose veins. Lasers in Surgery and Medicine 31:257-262 Endovenous.

Coughlin-L-B, Gandy-R, Rosser-S, De-Cossart-L. 2000 Factors associated with varicose veins in pregnant women. Phlebology 16:167-169 Pregnancy.

Kocakoc-E, Kiris-A, Orhan-I, Bozgeyik-Z, Kanbay-M, Ogur-E. 2002 Incidence and importance of reflux in testicular veins o f healthy men evaluated with colour duplex sonography. Journal o f Clinical Ultrasound 30:282-287 Testicular vein.

Silva-M-A, Deen-K-I, Femando-D-J-S, Sheriffdeen-A-H. 2002 The internal jugular vein valve may have a significant role in the prevention o f venous reflux: Evidence from live and cadaveric human subjects. Clinical Physiology and Functional Imaging 22:202-205 Internal jugular vein.

Belcaro-G, Nicolaides-A-N, Cesarone-M-R, De-Sanctis-M-T, Incandela-L, Errichi-B-M, Ricci-A, Georgiev-M, Vasdekis-S, Christopoulos-D, Rulo-A, Labropoulos-N, Malouf-M, Myers-K, Lennox-A, Venniker-R, Veller-M, Caizzi-N.2002 Flush ligation o f the sapheno-femoral junction vs. simple, distal ligation. A randomised, 10-year, follow-up. The safe study. Angeiologie 54:19-23 Flush ligation vs. distal ligation.

Weiss-R-A, Weiss-M-A. 2002 Controlled radiofrequency endovenous occlusion using a unique radiofrequency catheter under duplex guidance to eliminate saphenous varicose vein reflux: A 2-year follow-up. Dermatologie Surgery 28:38-42 New technique.

Mendoza-E. 2001 Topographic anatomy o f the great saphenous vein: An ultrasonic study and its surgical consequences. 2001 Phlebologie 30:140-144 Topographic study.

Dauplaise-T-L, Weiss-R-A. 2001 Duplex-guided endovascular occlusion of refluxing saphenous veins. Journal o f Vascular Technology 25:79-82 Endovascular

Daher-A, Jones-Y, da-Silva-A-F. 2001 The role o f popliteal vein incompetence in the diagnosis o f saphenous-popliteal reflux using continuous wave Doppler. European Journal o f Vascular and Endovascular Surgery 21:350-352 Deep vein reflux.

Rutherford-E-E, Kianifard-B, Cook-S-J, Holdstock-J-M, Whiteley-M-S. 2001 Incompetent perforating veins are associated with recurrent varicose veins. European Journal o f Vascular and Endovascular Surgery 21:458-460 IPV associated with recurrence

Spitz-G-A, Braxton-J-M, Bergan-J-J. 2000 Outpatient varicose vein surgery with transilluminated powered phlebectomy. Vascular Surgery 34:547-555 Outpatients phlebectomy.

Staszkiewicz-W, Madycki-G, Grzegrzolka-J, Hendiger-W. 2000 The value o f thermography in the preoperative mapping of primary and recurrent varicose veins. Phlebologie 29:129-133 Thermography.

Incandela-L, Belcaro-G, Nicolaides-A-N, Agus-G, Errichi-B-M, Cesarone-M-R, De-Sanctis-M-T, Ricci-A, Sabetai-M, Mondani-P, De-Angelis-R, Bavera-P, Griffin-M, Geroulakos-G. 2000. Superficial vein valve repair with a new external valve support (EVS): The IMES (International Multicenter EVS Study). Angiology 5LS39-S52. Valve repair

224

Belcaro-G, Nicolaides-A-N, Ricci-A, Dugall-M, Errichi-B-M, Vasdekis-S, Christopoulos-D. 2000 Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in superficial venous incompetence: A randomized, 10-year follow-up trial - Final results. Angiology 51:529-534 Endovascular sclerotherapy.

Min-R-J, Navarro-L, Bergan-J-J. 2000 Transcatheter duplex ultrasound-guided sclerotherapy for treatment o f greater saphenous vein reflux: Preliminary report. Dermatologie Surgery (26):410-414 Sclerotherapy.

Kim-J, Richards-S, Kent-P-J. 2000 Clinical examination of varicose veins - A validation study. Annals o f the Royal College o f Surgeons o f England 82:171-175 Clinical examination.

De-Maeseneer-M-G, Tielliu-I-F, Van-Schil-P-E, De-Hert-S-G, Eyskens-E-J. 1999 Clinical relevance of neovascularisation on duplex ultrasound in the long-term follow-up after varicose vein operation. Phlebology 14:118-122 Neovascular.

Gibbs-P-J, Foy-D-M-A, Darke-S-G. 1999 Reoperation for recurrent saphenofemoral incompetence: A prospective randomised trial using a reflected flap of pectineus fascia. European Journal o f Vascular and Endovascular Surgery 18:494-498 Technique

Ricci-S, Caggiati-A. 1999 Does a double long saphenous vein exist? 1999 Phlebology 14:59-64 Double GSV

Ricci-S, Caggiati-A. 1999 Echoanatomical patterns o f the long saphenous vein in patients with primaryvarices and in healthy subjects. Phlebology 1454-58Anatomy

Pocek-M, Guazzaroni-M-R, Sodani-G, Guazzaroni-M-N, Cancellieri-R, Sakr-A-M-A, Simonetti-G. 1999 Four years' follow-up results o f three different percutaneous treatments for male varicocele Phlebology 14:48-53 Varicocoele.

Turton-E-P-L, Scott-D-J-A, Richards-S-P, Weston-M-J, Berridge-D-C, Kent-P-J, Kester-R-C. 1999 Duplex-derived evidence o f reflux after varicose vein surgery: Neoreflux or neovascularisation? European Journal o f Vascular and Endovascular Surgery 17:230-233 Neo-vascularisation

Gasser-G, Mildner-A, Hilbe-G. 1998 Re-exploration o f the saphenofemoral junction: Surgical technique and results.Phlebologie 27:185-188 Technique

Hilbe-G, Neuhauser-B, Mildner-A. 1998 Five year results after surgical therapy of recurrent varicose veins. Vasomed 10:255-257 Recurrent W .

Darke-S-G, Vetrivel-S, Foy-D-M-A, Smith-S, Baker-S. 1997 A comparison o f duplex scanning and continuous wave Doppler in the assessment o f primary and uncomplicated varicose veins. European Journal o f Vascular and Endovascular Surgery 14:457-461

Zamboni-P, Cappelli-M, Marcellino-M-G, Murgia-A-P, Pisano-L, Fabi-P. 1997 Does a varicose saphenous vein exist? Phlebology 12:74-77 Saphenous vein.

Perrin-M. 1997 Surgical repair o f varicose veins of the lower limbs by saphenous stripping. Annales deChirurgie 51:735-744Stripping

Dixon-P-M. 1996 Duplex ultrasound in the pre-operative assessment o f varicose veins. Australasian Radiology 40:416-421 Pre-operative duplex.

225

Pleass-H-C-C, Holdsworth-J-D. 1996 Audit o f introduction o f hand-held Doppler and duplex ultrasound in the management o f varicose veins. Annals o f the Royal College o f Surgeons of England 78:494-496 Hand held Doppler.

Torngren-S, Hjertberg-R, Rosfors-S, Bremme-K, Eriksson-M, Swedenborg-J. 1996 The long-term outeome o f proximal vein thrombosis during pregnancy is not improved by the addition o f surgical thrombectomy to anticoagulant treatment.European Journal o f Vascular and Endovascular Surgery 12:31-36 Thrombosis.

Kanter-A, Thibault-P. 1996 Saphenofemoral incompetence treated by ultrasound-guided sclerotherapy.Dermatologie Surgery 22:648-652Sclerotherapy.

Tong-Y, Royle-J. 1996 Recurrent varicose veins after short saphenous vein surgery: A duplex ultrasound study. Cardiovascular Surgery 4:364-367 Short saphenous vein.

Mastroroberto-P Chello-M, Zofrea-S, Cirillo-F, Marchese-A-R, Comerota-A-J. 1996 Preliminary experience with cryopreserved saphenous vein allografts as a conduit for femoropopliteal revascularization. Vascular Surgery 30:103-107 Fem-pop graft.

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Danielsson G, Jungbeck C, Peterson K, Norgren L 2002 A randomised controlled trial o f micronised purified flavonoid fraction vs. placebo in patients with chronic venous disease. European Journal of Vascular & Endovascular Surgery 23(l):73-6. Medical trial.

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Makarova NP, Lurie F, Hmelniker SM 2001 Does surgical correction of the superficial femoral vein valve change the course o f varicose disease?[see comment].Journal o f Vascular Surgery 33(2):361-8 Valvular correction.

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S, Simmons MJ, Galland RB, Magee TR 2001 Is a palpable short saphenous vein a useful clinical sign in varicose vein assessment?Annals o f the Royal College o f Surgeons o f England Mar;83(2): 105-7. Short saphenous vein.

Cesarone MR, Belcaro G, Rulo A, Griffin M, Ricci A, Ippolito E, De Sanctis MT, Incandela L, Bavera P, Cacchio M, Bucci M 2001 Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcP02-C 02, and leg volumetry. Angiology 52:S45-8. Microcirculation.

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Incandela L, Belcaro G, De Sanctis MT, Cesarone MR, Griffin M, Ippolito E, Bucci M, Cacchio M 2001 Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined mierocirculatory model. Angiology 52:S61-7. Medical Treatment.

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Arcangeli P 2000 Pycnogenol in chronie venous insufficiency. Fitoterapia 71(3):236-44. Not relavent

Jantet G 2000 RELIEF study: first consolidated European data. Reflux assEssment and quaLity o f life improvement with micronized Flavonoids. Angiology 51(l):31-7.

Incandela L, Belcaro G, Nicolaides AN, Agus G, Errichi BM 2000 Superficial vein valve repair with a new external valve support (EVS) Angiology 51(8):S39-S52.Valve repair.

Incandela L, Belcaro G, Nicolaides AN, Agus G, Errichi BM, Cesarone MR, De Sanctis MT, Ricci A, Sabetai M, Mondani P, De Angelis R, Bavera P, Griffin M, Geroulakos G 2000 Superficial vein valve repair with a new external valve support (EVS). The IMES (International Multicenter EVS Study). Angiology 5 l(8):S39-52.Valvular repair.

Pocek M, Guazzaroni MR, Sodani G, Guazzaroni MN, Cancellieri R, Sakr AMA, Simonetti G 1999 Four years' follow-up results o f three different percutaneous treatments for male varicocele. Phlebology, 14(2):48-53. Varicocoele.

Fitridge RA, Dunlop C, Raptis S, Thompson MM, Leppard P, Quigley F 1999 A prospective randomized trial evaluating the haemodynamic role o f ineompetent calf perforating veins. Australian & New Zealand Journal o f Surgery 69(3):214-6.Haemodynamics.

Gibbs PJ, Foy DM, Darke SG 1999 Reoperation for recurrent saphenofemoral incompetence: a prospective randomised trial using a reflected flap of pectineus fascia. European Journal o f Vascular & Endovascular Surgery 18(6):494-8.Recurrent technique.

Dwerryhouse S, Davies B, Harradine K, Earnshaw JJ 1999 Stripping the long saphenous vein reduces the rate o f reoperation for recurrent varicose veins: five-year results o f a randomized trial. J o f Vase Surg 29(4):589-92. Saphenous surgery.

Kent PJ, Weston MJ 1998 Duplex scanning may be used selectively in patients with primary varicose veins. Annals o f the Royal College of Surgeons o f England 80(6):388-93. Selective duplex.

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GM, Wolferth CC 1996 A correlation o f air plethysmography and colour-flow-assisted duplex scanning in the quantification o f chronic venous insufficiency Journal o f Vascular Surgery 24(5):750- 754. Weingarten MS, Czeredarczuk M, Scovell S, Branas CC, Mignogna Phlethysmography.

Cloarec M, Clement R, Griton P 1996 A double-blind clinical trial o f hydroxyethylrutosides in the treatment o f the symptoms and signs o f chronic venous insufficiency. Phlebology, ll(2):76-82 Medical treatment.

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Belcaro G, Cesarone MR, de Sanctis MT, Incandela L, Laurora G, Février B, Wargon C, De Gregoris P 1995 Laser Doppler and transcutaneous oximetry: modern investigations to assess drug efficacy in chronic venous insufficiency. International Journal o f Microcireulation: Clinical & Experimental 15(l):45-9. Oxymetry.

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