introduction and outline of the thesis introduction and... · introduction and outline of the...
TRANSCRIPT
Introduction and outline of the thesis
Intr
oduc
tion
and
outli
ne o
f the
thes
is
11
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
12
Intr
oduc
tion
and
outli
ne o
f the
thes
is
13
(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.
14
Intr
oduc
tion
and
outli
ne o
f the
thes
is
15
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
16
Intr
oduc
tion
and
outli
ne o
f the
thes
is
17
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.
18
Intr
oduc
tion
and
outli
ne o
f the
thes
is
19
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.