Università di Roma “La Sapienza” - chped.itchped.it/gico/napoli/REL WILMS COZZI NAPOLI...

Prof. Denis A. Cozzi

Chirurgia nephron-sparing per tumorirenali primitivi in età pediatrica.

Università di Roma “La Sapienza”U.O.C. Chirurgia Pediatrica - Policlinico Umberto I

Direttore: Prof Francesco Cozzi

Clinical and experimental data suggest that hyperfiltrationfollowing removal of a critical mass of renal tissue causes a progressive glomerular damage.

Background

Anderson KD et al. J Urol, 1985

Patients with a reduction of renalmass of more than 50% are at increased risk of renal failure.

Background (cont.)

Novick et al. N Engl J Med, 1991

Aim of the study

To evaluate the feasibility and safety of nephron-sparing surgery (NSS) in childrenwith syncronous bilateral Wilms’ tumour(BWT).

Review of available reports fromWilms’ tumour major paediatriconcology cooperative groups

Methods

NWTS-1 (1969-’73)

NWTS-2/3 (1974-’86)

NWTS-4 (1986-’94)

UKCCS (1980-’95)

SIOP/Ger (1994 /’01)

Studies No. of Patients

PreoperativeChemotherapy (%)

30

185

98

71

89

10

41

70

81

100

Results of treatment for bilateral Wilms’ tumor

Cozzi DA and Zani A. Seminars Ped Surg, 2006

NWTS-1 (1969-’73)

NWTS-2/3 (1974-’86)

NWTS-4 (1986-’94)

UKCCS (1980-’95)

SIOP/Ger (1994 /’01)


No. of kidneys receiving NSS (%)

30

185

98

71

89

23

51

72

42

76



NWTS-1

NWTS-2 and 3

NWTS-4UKCCS

SIOP/Ger

Overall survival rate (%)

87

83

92-

-

Mean follow-up (years)2 4-5 6-10

-

73

82-

83

-

70

-69

-Cozzi DA and Zani A. Seminars Ped Surg, 2006


NWTS-1 (1969-’73)

NWTS-2/3 (1974-’86)

NWTS-4 (1986-’94)

UKCCS (1980-’95)

SIOP/Ger (1994 /’01)


NephrectomyNo. patients (%)

30

185

98

71

89

67

83

55

72

45



In children with syncronous BWT, NSS does not impair the excellentoutcome.

Conclusion


Conclusion (cont.)

Nearly half of the patients remainwith less than 50% of renalparenchyma.


A more aggressive NSS approach seems justified.

Implication


Background

The major emphasis of both the NWTSG and SIOP is reducing the morbidity of treatment for low-risk patients while maintaining the excellent survival rate.

In nephrectomized children, the risk of renal failure due to hyperfiltration is considered low.

Nephron-sparing surgery for children with unilateral renal tumour and normal contralateral kidney is a controversial issue.

Background

Wilms’ tumor : survival rate(SIOP-9: 1987-92)

Months

0%

20%

40%

60%

80%

100%

4 8 12 16 20 24 32 36

I fav.I stand/ana.II N0IIN1+IIIIVunfav.

Adults after partial removal of a solitary kidney


0

1

2

3

Amount of kidney remaining (%) 72 ± 438 ± 16 60 ± 19

Uri

nar

y p

rote

ing/day

p =0.006

Adults after partial removal of a solitary kidney


124 ± 4663 ± 2 81 ± 20

g/day

Uri

nar

y p

rote

in

Follow-up (months)

p =0.0005

0

1

2

3

0

40

80

120

Long-term follow-up of patients undergone unilateral nephrectomy in childhood

p =N.S.

Robitaille et al. Lancet, 1985Interval since nephrectomy (years)

25 - 3317 - 24

Creatinine clearance (ml/min/1.73m2)

Wikstad et al. Pediatr Nephrol, 1988

Adults born with unilateral agenesis or nephrectomized in childhood

150

125

100

75

50

25

026-407-15 16-25

Urinary albumin (µg/1.73m2/min)150

125

100

75

50

25

0

GFR (ml/1.73m2/min)

Follow-up (years)

Longitudinal changes of postoperativeserum creatinine standard deviation scores

1 2 3 4 5 6 7 8 9

-1

0

1

2

Follow-up (years)

Seru

mcr

eatin

ine

SDS

r2=0.49p= 0.02

(Values are Means ± SE)

Cozzi F et al. J Urol, 2005


Enucleative Surgery for Stage I NephroblastomaWith a Normal Contralateral Kidney.

Nephron-Sparing Surgery for Unilateral Primary Renal Tumour in Children.

Cozzi DA et al. J Ped Surg, 2001

Patient characteristics

(January 1992 – August 2006)Unilateral primary renal tumours (37 children)

Nephrectomy Nephron-sparing surgery

All stages Stage I

Event-free Survival 85 % Event-free Survival 100 %

Mean follow-up 8 yrs Mean follow-up 8 yrs

No of patients 26 No of patients 11

Pre-operative Two-drug regimen (SIOP)

Post-operative 1992-1995: Three-drug regimen

1996 - : Two-drug regimen

Nephron-Sparing Surgery Chemotherapy

11No. of patients

Nephron-Sparing Surgery Procedures

No. of tumour enucleation 7

No. of partial nephrectomy 5

LT (46%) RT (54%)

LT (57%) RT (43%)

LT (40%) RT (60%)

Oncocitoma

LT (62%) RT (38%)

LT (31%) RT (69%)


LT 25%

RT 75%

0

10

20

30

40

50

DMSA uptake of kidney remnant after NSS

Mean Follow-up15 mos. 5.6 yrs.

Split

rena

lfun

ctio

n(%

)

BAPS Meeting, Dublin 2005

0

10

20

30

40

50

Mean Follow-up15 mos. 5.6 yrs.

p = n.s.

Split

rena

lfun

ctio

n(%

)

DMSA uptake of kidney remnant after NSS


0 10 20 30 40 500

10

20

30

40

50

Ultrasound measured renal volume and DMSA measured renal function

Split renal function (%)

Split

rena

lvol

ume

(%)

r2 = 0.81p = 0.002


Following NSS, split renal function of the affected kidney remnant is satisfactory, stable, and well correlated with split renal volume.

Conclusion (i)


Creatinine (mg/dl) 0.79±0.03 0.63±0.03 0.001

Systolic pressure (mmHg) 112.5±8.6 100.0±9.1 <0.001

Dyastolic pressure (mmHg) 72.5±8.4 63.5±7.1 0.005

p valueNSS(10 patients)

Nephrectomy(16 patients)

Post-surgery interval (months) 71.9±41.9 65.3±38.6 0.35

Renal function and blood pressuremeasurements following surgery

(Values are Means ± SD)

Creatinine SDS 1.27±0.69 0.70±0.49 0.02

Systolic pressure SDS 0.72±0.74 -0.10±0.92 0.01

Dyastolic pressure SDS 0.87±0.77 0.19±0.62 0.01


Ablative renal surgery is followed by a progressive renal dysfunction.

Nephron sparing surgery has a renalfunction advantage over nephrectomy.

Conclusion (ii)


Nephron-sparing surgery in children with unilateral

renal tumour: a systematic literature review.

SIOP Meeting, Geneve 2006

To evaluate the oncological risk of NSS in children with primary renal tumour and normal contralateral kidney.

Aim of the study

Comprehensive review of the Literature:

Methods

Electronic search (MEDLINE, OVID, EMBASE)

Hand-search (reference lists of articles, abstracts from conference proceedings)

(1982 – 2005)Patients

No. of collected patients 124

No. of eligible studies 20

37

30

1310

8 7

2 25 5

2 1 1 10

20

40

German

yPor

tugal

Italy

Poland

Austri

a

The N

ether

lands

Switzer

land

Fran

ceUSA

Canad

aNew

Zeland

Austra

liaJa

pan

IndiaPatient per country

No.

of p

atie

nts

Results

Local recurrence 7 (5.6%)

No. of patients 124

Survival rate 95.1 %

Follow-up (mean)

Overall

≅ 4 yrs

Benign or “low-risk” Wilms’tumours

Local recurrence 0

No. of patients 17

Survival rate 100 %

Follow-up (mean) 3.6 yrs

No. of patients

Cystic nephroma 5

Cystic partially differentiated nephroblastoma

7

Congenital mesoblastic nephroma 4

Oncocytoma 1

Benign or “low-risk” Wilms’tumours

Stage I “Intermediate-risk”Wilms’ tumour

Local recurrence 4 (6.6 %)

No. of patients 60

Survival rate 98.3 %

Follow-up (mean) 4 yrs

No. of patients

Hyperplastic nephroblastomatosis 4

Beckwith-Wiedemann syndrome 2

Hemihypertrophy 1

Aniridia, hypospadias, cryptorchidism 1

Patients at increased risk of metachronous Wilms’ tumour

Local recurrence 0

No. of patients 32

Survival rate 94 %

Follow-up -

(no data on staging)“Intermediate-risk” Wilms’ tumour

Local recurrence 3 (20%)

No. of patients 15

Survival rate 80 %

“High-risk” or stage II / III “Intermediate- risk” Wilms’ tumour

Follow-up -

0

20

40

60

80

100

No.

of p

atie

nts

Preoperativechemotherapy

Primarysurgery

NSS for unilateral Wilms’ tumour: pre-op chemotherapy

Intermediate / High-risk WT

Benign / Low-risk WT

0

10

20

30

40

No.

of p

atie

nts

P =0.04

Complete nephrectomy

Partialnephrectomy

Preoperativechemotherapy

Primarysurgery

NSS and pre-op chemotherapy for Wilms’ tumour in horseshoe kidneys

Neville H et al. JPS 2002

In children with benign or “low / intermediate- risk” histology stage I WT and a normal opposite kidney, the oncological risk of NSS is low, probably because histology and staging are related to the biology of the tumour.

Conclusion (iii)

“A prospective trial of less aggressive intervention should be considered for select patients with unilateral WT and normal opposite kidney.”

Implication

Zani A et al. J Urol. 2005 Mar;173(3):946-8; discussion 948

Ross J, Cleveland, Ohio

GrazieSIUP Meeting, Ischia 2007

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