Introduction and outline of the thesis

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Diverticular disease is one of the most prevalent gastrointestinal disorders in Western

society, associated with incidences of 33% in the population over 45 years of age and

increasing to 66% in the population older than 85 years of age.1 Although diverticular

disease is more common among elderly patients, an important rise in incidence is noted

in the younger age groups.2 Approximately 10-25% of patients with asymptomatic

diverticulosis will develop acute diverticulitis; its presentation may vary from mild

complaints to a generalized peritonitis.

The pathogenesis of diverticula is related to two processes, weakening of the colonic

wall and increased intraluminal pressure.3 The weakening of the colonic wall is thought

to be due to the aging process and connective tissue disorders.4,5 Fibre deficiency and

abnormal colonic motility may be responsible for the increased intraluminal pressure.6

Typically for left-sided diverticulosis are false diverticula, which are small, mucosal

herniations that develop at the natural weak spots of the colon, where the vasa recta

reach the bowel wall. Other anatomic characteristics in diverticulosis are circular muscle

thickening, narrowing of the colonic lumen and shortening of the taeniae, known as

myochosis. Obstruction of diverticula by fecal matter might induce a cascade of events

including: distention of the sac, bacterial overgrowth, vascular compromise, and micro

or macro perforations. Clinical manifestations of diverticulitis are phlegmon, abscess,

peritonitis or fistula (see Figure 1).1 Late sequelae of diverticulitis are often the result of

post inflammatory alterations, like adhesions or stenosis.

The term ‘diverticular disease’ comprises a spectrum of conditions. Diverticulosis refers

to the presence of diverticula in the colon, mostly asymptomatic and localized in the

sigmoid colon. Diverticulitis refers to infection or inflammation of diverticula and can be

classified as: 1) complicated diverticulitis, associated with abscesses, perforation, fistula

or stenosis; 2) uncomplicated diverticulitis, associated with clinical episodes of fever,

pain, bloating and/or change in bowel habits, whereby imaging may show phlegmon or

small abscess, or no abnormalities at all; 3) acute diverticulitis, associated with the

requirement of an immediate admission or intervention, and that may be complicated or

uncomplicated. Nowadays, the diagnosis of acute diverticulitis and the extent of the

disease is confirmed by Computed Tomography, enhanced by intravenous and rectal

contrast.7,8 Colonoscopy is helpful in the elective setting when a stenosis is suspected or

for ruling out cancer. Traditionally, complicated diverticulitis is classified according to

Hinchey’s classification (see Figure 2), but other grading systems have been

proposed.9,10

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(Hinchey I and II) in middle aged and elderly, after a single episode in young patients or

in those patients who had developed complications, such as stenosis or fistulas.14

Recently, these recommendations have been challenged, because new data on the

natural history of diverticulitis have shown that most perforations do not occur after

The treatment of diverticular disease depends on the severity of the disease. Mild cases

of diverticulitis such as phlegmon or small abscesses (Hinchey I) can be treated

conservatively, with or without antibiotics and fluid diet. Larger abscesses (Hinchey II)

can be relieved by CT-guided percutaneous drainage.11 After a successful conservatively

treated episode, there is a risk of recurrence of disease and complications, such as

stenosis or fistulas to hollow organs (bladder or vagina). Purulent (Hinchey III) or fecal

(Hinchey IV) peritonitis results from a perforation and is associated with high morbidity

and mortality (10-35%). Under these severe circumstances, acute surgical intervention is

warranted. Hartmann’s procedure used to be the treatment of choice, but recently

primary anastomosis or laparoscopic lavage are used increasingly.12,13

In 2000 the American Society of Colon and Rectal Surgeons (ASCRS) presented practice

guidelines for preventing recurrence of diverticulitis with subsequent perforation. It was

advised to perform an elective sigmoid resection after two episodes of acute diverticulitis

Figure 1 The pathogenesis of diverticulitis Figure 2 Hinchey’s classification

Copyright © 2007 Massachusetts Medical Society. All rights reserved.

Copyright © 2007 Massachusetts Medical Society. All rights reserved.

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seem indispensable. In Chapter 1 all current classifications on diverticular disease will

be reviewed. The result is a proposal of a comprehensive classification that provides a

useful practice parameter for diagnostic tools and treatment modalities.

The indications for elective sigmoid resections for diverticular disease are evolving.

Recent publications show that perforations due to diverticulitis or other acute surgical

indications occur more often in patients without a history of diverticular disease.

Moreover, the course of diverticular disease after conservative treatment tends to be

mild with very low rates of recurrences and complications.15-17 Thereby suggesting that

elective resections should be restricted to complicated cases only. In Chapter 2, a

retrospective analysis is performed to clarify the natural history of diverticular disease

and to identify clinical risk factors that may be associated with a more hazardous course

of diverticular disease.

The rising incidence of diverticular disease among young patients is alarming, especially

because several authors claim a more virulent course of the disease in this group.23 As a

result, the management of diverticular disease in young patients remains controversial.

Less favorable outcomes in elderly patients have also been published, but the increased

morbidity and mortality rates in the high age groups might mainly be determined by

their comorbid conditions.24 Chapter 3 outlines the relation of the age factor associated

with the course of diverticular disease and its treatment.

Since diverticular disease accounts for 14.000 hospital admissions in the Netherlands

each year, it is important to evaluate the implementation of these developments for

daily practice in terms of the diagnostic tools, the indications for surgery, and the

treatment modalities. Chapter 4 addresses current surgical practice of diverticular

disease in The Netherlands.

PART II – The Sigma-trial

Over the last two decades, laparoscopic surgery has gained popularity in the treatment

of diverticular disease. Particularly in an elective setting, certain beneficial effects on

postoperative outcomes of laparoscopic sigmoid resections have been reported

following non-randomized comparison studies.20,21 In Chapter 5, the Sigma-trial protocol

is described, this is the first study designed as a randomized control trial to compare the

impact of laparoscopic versus open sigmoid resections on postoperative complication

rates in patients with symptomatic diverticulitis.

recurrences, but at the first attack of acute diverticulitis. Furthermore, conservative

management of recurrent non-perforated diverticulitis is associated with low morbidity

and mortality rates.15-17 These new insights resulted in a revision of the ASCRS guidelines

in 2006, advocating a more individual and conservative approach.18

In an elective setting, conventional open sigmoid resections for diverticular disease

have been associated with high postoperative complication rates and a mortality rate of

two to five percent.19 In the early nineties, laparoscopic approaches for colorectal surgery

were already introduced to minimize surgical trauma and subsequently reduce morbidity

and shorten hospitalization. Several authors have published non-randomized

comparative studies, reporting beneficial outcomes following laparoscopic sigmoid

resections for treating divericular disease.20-22 Confirmation of these advantages of the

laparoscopic approach in a randomized control trial is called for, especially when the

more stringent indications for elective surgery are considered.

Aim of the thesis

• To review current classifications of diverticular disease, in perspective of new insights

in its natural history, novel imaging modalities and therapeutic options

• To evaluate the indications for elective surgery in diverticular disease

• To identify risk factors that may be associated with a more complicated course of

diverticular disease

• To compare the impact of laparoscopic versus open elective sigmoid resections on

postoperative complication rates in patients with symptomatic diverticular disease

Outline of the thesis

Part I of this thesis addresses the current management of diverticular disease in relation

to classifications, indications for elective surgery, risk-factors for complications and

clinical practice. Part II describes the Sigma-trial, a randomized control trial comparing

laparoscopic versus open elective sigmoid resections in patients with symptomatic

diverticular disease.

PART I – Current management of diverticular disease

The definition and classification of such a complex condition like diverticular disease

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References

1. Jacobs DO. Clinical practice. Diverticulitis.

N Engl J Med 2007; 357:2057-2066.

2. Etzioni DA, Mack TM, Beart RW, Jr. et al. Di-

verticulitis in the United States: 1998-2005:

changing patterns of disease and treat-

ment. Ann Surg 2009; 249:210-217.

3. West AB, Losada M. The pathology of di-

verticulosis coli. J Clin Gastroenterol 2004;

38:S11-S16.

4. Mimura T, Bateman AC, Lee RL et al. Up-

regulation of collagen and tissue inhibi-

tors of matrix metalloproteinase in colonic

diverticular disease. Dis Colon Rectum

2004; 47:371-378.

5. Wess L, Eastwood MA, Wess TJ et al. Cross

linking of collagen is increased in colonic

diverticulosis. Gut 1995; 37:91-94.

6. Ritsema GH, Thijn CJ, Smout AJ. [Motility

of the sigmoid in irritable bowel syndrome

and colonic diverticulosis]. Ned Tijdschr

Geneeskd 1990; 134:1398-1401.

7. Ambrosetti P, Jenny A, Becker C et al. Acute

left colonic diverticulitis--compared per-

formance of computed tomography and

water-soluble contrast enema: prospec-

tive evaluation of 420 patients. Dis Colon

Rectum 2000; 43:1363-1367.

8. Liljegren G, Chabok A, Wickbom M et al.

Acute colonic diverticulitis: a systematic

review of diagnostic accuracy. Colorectal

Dis 2007; 9:480-488.

9. Hinchey EJ, Schaal PG, Richards GK. Treat-

ment of perforated diverticular disease of

the colon. Adv Surg 1978; 12:85-109.

10. Kohler L, Sauerland S, Neugebauer E. Diag-

nosis and treatment of diverticular disease:

results of a consensus development con-

ference. The Scientific Committee of the

European Association for Endoscopic Sur-

gery. Surg Endosc 1999; 13:430-436.

11. Kaiser AM, Jiang JK, Lake JP et al. The man-

agement of complicated diverticulitis and

the role of computed tomography. Am J

Gastroenterol 2005; 100:910-917.

12. Myers E, Hurley M, O’Sullivan GC et al.

Laparoscopic peritoneal lavage for gener-

alized peritonitis due to perforated diver-

ticulitis. Br J Surg 2008; 95:97-101.

13. Karoui M, Champault A, Pautrat K et al.

Laparoscopic peritoneal lavage or primary

anastomosis with defunctioning stoma for

Hinchey 3 complicated diverticulitis: re-

sults of a comparative study. Dis Colon

Rectum 2009; 52:609-615.

14. Wong WD, Wexner SD, Lowry A et al. Prac-

tice parameters for the treatment of sig-

moid diverticulitis--supporting documen-

tation. The Standards Task Force. The

American Society of Colon and Rectal Sur-

geons. Dis Colon Rectum 2000; 43:290-

297.

15. Chapman J, Davies M, Wolff B et al. Com-

plicated diverticulitis: is it time to rethink

the rules? Ann Surg 2005; 242:576-581.

16. Salem TA, Molloy RG, O’Dwyer PJ. Prospec-

tive, five-year follow-up study of patients

with symptomatic uncomplicated diver-

ticular disease. Dis Colon Rectum 2007;

50:1460-1464.

17. Collins D, Winter DC. Elective resection for

diverticular disease: an evidence-based

review. World J Surg 2008; 32:2429-2433.

18. Rafferty J, Shellito P, Hyman NH et al. Prac-

tice parameters for sigmoid diverticulitis.

Dis Colon Rectum 2006; 49:939-944.

19. Oomen JL, Engel AF, Cuesta MA. Outcome

of elective primary surgery for diverticular

disease of the sigmoid colon: a risk analy-

sis based on the POSSUM scoring system.

Colorectal Dis 2006; 8:91-97.

Chapter 6 reports the short-term results of the Sigma-trial. Primary endpoints included

are postoperative mortality and postoperative complications within 30 days from

surgery. Since this study is the first randomized controlled trial comparing laparoscopic

and open sigmoid resections for diverticular disease, overwhelming reactions followed

its publication. Valuable comments in two letters to the editor are added to this

manuscript, mainly addressing the adoption of enhanced recovery programs. The letters

and reactions are depicted in Chapters 6.1 and 6.2.

The results described in Chapter 6 comprise a follow-up period of six weeks. Data on late

outcomes after laparoscopic surgery for diverticular disease is scarce, although a

reduction in incisional hernias and recurrent disease might only be demonstrated after

several months. The mid-term results of the Sigma-trial can be found in Chapter 7.

There is compelling evidence that laparoscopic sigmoid resections provide several

advantages, but serious concerns regarding higher medical costs remain.25 It has been

suggested that the longer operative procedures and the wide use of disposable products

might be partially compensated by the shorter hospital stay. In Chapter 8 the direct

healthcare costs of patients with symptomatic diverticular disease randomized for either

laparoscopic or open elective sigmoid resection are compared. Furthermore, a cost-

effectiveness analysis of the laparoscopic approach in comparison with open sigmoid

resections is presented.

Finally the results from these studies will be put into perspective of a general discussion

in the concluding chapter of this thesis.

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20. Alves A, Panis Y, Slim K et al. French multi-

centre prospective observational study of

laparoscopic versus open colectomy for

sigmoid diverticular disease. Br J Surg

2005; 92:1520-1525.

21. Schwandner O, Farke S, Fischer F et al.

Laparoscopic colectomy for recurrent and

complicated diverticulitis: a prospective

study of 396 patients. Langenbecks Arch

Surg 2004; 389:97-103.

22. Scheidbach H, Schneider C, Rose J et al.

Laparoscopic approach to treatment of

sigmoid diverticulitis: changes in the spec-

trum of indications and results of a pro-

spective, multicenter study on 1,545 pa-

tients. Dis Colon Rectum 2004; 47:1883-

1888.

23. Janes S, Meagher A, Frizelle FA. Elective

surgery after acute diverticulitis. Br J Surg

2005; 92:133-142.

24. Comparato G, Pilotto A, Franze A et al. Di-

verticular disease in the elderly. Dig Dis

2007; 25:151-159.

25. Senagore AJ, Duepree HJ, Delaney CP et al.

Cost structure of laparoscopic and open

sigmoid colectomy for diverticular disease:

similarities and differences. Dis Colon Rec-

tum 2002; 45:485-490.