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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Background and Aim  The incidence and therefore complications of (sigmoid) diverticular disease are increasing.

Methods  Review of current literature.

Results  From all patients, 15% will develop diverticulitis, 5% complications and 5% diverticular bleeding. Diagnosis is established with computerised tomography. Colonoscopy is needed to rule out malignancy. NSAIDs increase the risk of perforation; steroids, diabetes, collagen vascular disease and immune compromised are associated with complicated disease and death. In mild diverticulitis, antibiotics are recommended. In complicated disease with abscesses, <5 cm antibiotics are sufficient. Larger abscesses are drained under computerised tomography-guidance. Peritonitis forms an indication for surgery. Diverticulitis recurrence rate is around 30%, most are uncomplicated. Recurrence after surgery is around 10%. Elective surgery is reserved for fistula closure and obstruction. The need for elective surgery to prevent recurrence has diminished because of new insights. Important is to identify risk groups. New issues are the possible relationship between diverticulitis and cancer, segmental colitis associated with diverticulitis, and treatment of diverticulitis with mesalazine and probiotics.

Conclusions  Uncomplicated diverticulitis is treated medically. Complicated diverticulitis with small abscesses is treated with antibiotics while larger abscesses are drained with computerised tomography-guided puncture. Emergency surgery is reserved for peritonitis, elective surgery for fistula/stenosis. Surgery to prevent recurrence is indicated only in selected cases (e.g. immune compromised).


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Diverticulosis and therefore diverticulitis are increasing, what consequently increases complication rate. The prevalence of perforated sigmoid in diverticular disease in the western countries has increased from 2.4/100.000 in 1986 to 3.8/100.000 in 2000.1 Another distressing factor is that during the last 20 years, standardized annual age rates of admission and surgical intervention have increased by 16% from 20.1/100.00 to 23.2/100.000, whereas in-patient and population mortality remained unchanged.2

The terminology of diverticular associated disease needs to be used adequately in order to avoid confusion3 (Table 1).

Table 1.   Terminology of diverticulosis
Diverticula:many pockets through the muscle layers
Diverticulum:a single defect through the muscle layer
Diverticulosis:presence of diverticula that are asymptomatic
Diverticular disease:diverticula associated with symptoms
Diverticulitis:evidence of diverticular inflammation (fever, tachycardia) with or without localized symptoms or signs
Complicated diverticulitis:perforation (into peritoneal cavity), abscess, fistula, stricture/obstruction

Diverticulosis

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Anatomy

The diverticula of diverticulosis are false diverticula, due to pulsion of herniating mucosa and submucosa through the muscle layer. This is contrast to the congenital diverticula, which contain all bowel layers. Diverticula tend to occur at 4 points around the circumference of the colon where the vasa rectae penetrate the circular muscle: each side of the mesenteric taenia, and on the mesenteric border of the two antimesenteric taenia.4

Epidemiology

Although diverticulosis was noticed in the 19th century, the Mayo brothers reported the first operation for diverticular disease in the United States in 1907.5 The prevalence of diverticulosis in the US in the early 20th century was reported as 5% to 10%.6 In 1969 autopsy series reported 10% to 66% presence, depending on age.7 There is an increase in the prevalence of diverticulosis with age, from less than 10% in those under the age of 40 to 50%–70% among those over the age of 70.8–10 There is no clear overall difference in prevalence between women and men. Diverticula are located in 95% in the sigmoid, in 35% additionally also proximal, 7% are pancolonic.11 There seem also to be a striking geographical variation in the prevalence of diverticulosis, as Asian nations report much lower prevalences.6, 12 One differential aspect between diverticular disease in the West and Asia is the predominant right location in the latter. A right colon location was observed in 83% of patients, whereas only 17% had lesions located exclusively in the left colon.13 However recently, due to decreased fibre intake, both an increase in right-sided diverticulosis as well as an increase in left-sided diverticulosis has been observed in developing Asian countries.14

Pathophysiology

The pathophysiology is related to a low fibre diet, altered motility and colonic wall resistance.

The major hypothesis concerning the propensity to form diverticula focuses on dietary fibre.9, 13, 15 Most studies support a strong inverse relationship between population fibre intake and the prevalence of diverticulosis. One study of approximately 47 000 men found a relative risk of 0.58 for the presence of diverticulosis comparing the quintile with the highest average fibre intake with the quintile with the lowest intake.15 Diverticulosis seems to become more common among groups that move to western countries or that adopts a western-style diet.16 Moreover, other studies have also pointed to the fact that diverticulosis seems to be less common among vegetarians.17 The role of fibre in the pathogenesis of diverticulosis likely rests on its influence on colonic pressures. The inverse relationship between colonic diameter and pressure is explained by the Law of Laplace, in which kT/R (where P is the pressure, k is a constant, T is the wall tension, and R is the bowel radius). Fibre may mediate the generation of lower pressures in the sigmoid colon by increasing the bulk of stool; bulkier stools may discourage segmentation and increase the diameter of the sigmoid colon, resulting in lower pressures. Furthermore, the decrease in soluble fibre may also have important physiologic effects, altering gut flora in particular, which may have significant immune consequences central to the pathophysiology of diverticulitis.18

Motility seems to play an important role. Most studies indicate that patients with diverticula have higher resting pressures and postprandial colonic pressures than controls.10, 19 However, normal pressures have been found in another study.20 More recent study showed that in early disease high pressures and irregular slow waves can be found, but that in late disease these features have normalized.21 In addition, diverticular colon has exaggerated segmentation.22 Segmentation leads to high pressure, which is the highest in the part of the colon with the smallest diameter, the sigmoid colon, which is the part most often involved by diverticulosis. Furthermore, interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurons appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.23

Another aspect is the colonic wall resistance. The structure of colons with diverticula is often marked by myochosis, with thickened circular muscle, shortened taenia, and narrow lumens. On a microscopic level, colons with diverticulosis may have increased elastin in the taenia24 and structural changes in collagen that mimic those seen with aging.25 This concerns not so much the total amount of collagen, but the cross linking and an increase in type 3 fibres.19, 26 The involvement of these changes in the development of diverticulosis is supported by the observation that diverticulosis tends to occur at younger age in patients with connective tissue diseases such as Ehlers-Danlos or Marfans syndromes.26

Relationship with diverticulitis

Among patients with diverticulosis, approximately 70% will remain free of major diverticular complaints. Some patients with diverticulosis will complain of a variety of vague symptoms, including cramping, bloating, flatulence, or irregular defecation (diverticular disease); of these, many likely have irritable bowel syndrome (IBS). Approximately 15% to 25% of patients with diverticulosis will develop diverticulitis, and 5% to 15% will develop diverticular bleeding. Among patients with diverticulitis, approximately 75% will have simple diverticulitis and 25% will have diverticulitis complicated by abscess, obstruction, perforation, or fistula formation.

The only intervention with evidence to suggest that it reduces risk of diverticular disease and its complications is a high fibre diet, which may reduce the risk of developing diverticular disease15, 27 and may also reduce the risk of later complications among patients with diverticulosis.9

Diverticular disease

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

A proportion of patients with diverticulosis reports recurrent colicky abdominal pain, and/or changed bowel habits without any findings consistent with diverticulitis, which has been called uncomplicated symptomatic diverticulosis. Occurrences of abdominal pain in these patients may be related to abnormal colon motility. In a controlled study, episodes of cramping abdominal pain were coincident with a regular colonic contractile pattern, as assessed by 24-h colonic manometry.23 Considering the high prevalence of IBS (5–25%) and diverticulosis (10–66%), both conditions may coexist frequently.10, 28 One study showed heightened visceral perception of the rectosigmoid (not only in the area with diverticula), not due to altered compliance of the bowel wall.29 This situation of hyperperception resembles IBS. In a community-based survey, a study of 261 patients with diverticulosis diagnosed by barium enema, observed that 14% met the Rome I criteria for IBS, 36% had recurrent short-lived pain, and 19% had episodes of prolonged pain lasting for 1 day or longer, which in more than 60% required emergency medical attention.30 In more than half of the patients with prolonged pain, there was also short-lived pain as part of their usual bowel habit. The authors concluded that recurrent short-lived pain (similar to that seen in IBS) often occurs in patients who have experienced prolonged pain attributable to diverticulitis. However, the presence of colonic diverticula does not seem to change the natural history of IBS.28 The connection and/or differences between uncomplicated symptomatic diverticulosis and IBS should be further clarified in future studies. A high-fibre diet is recommended for patients with symptomatic uncomplicated diverticulosis.10

Although there is theoretically no rationale for the use of antibiotics in this group of patients, this has been performed. Three Italian randomized trials comparing daily fibre supplementation alone or with cyclic administration of oral rifaximin for 12 months in 168 and 968 patients31, 32 or 24 months in 307 patients33 showed that significantly more patients in the rifaximin group were free of symptoms, and in one of the studies the incidence of complications (mainly diverticulitis) was also reduced. Although the mechanism for such improvement is unknown, the authors postulate that it could be related to a reduction in gas production and bacterial overgrowth.

The same applies for the use of Mesalazine in several Italian studies. In recent large study of 286 patients, who were randomized treated 10 days a month with either rifaximine (200 or 400 mg twice a day) or Mesazaline (400 or 800 mg twice a day), the patients treated with Mesazaline improved more on a global symptom score.34 Daily prescription may even be more effective.35 Reduction of inflammation due to altered bacterial flora is thought to play a role.

In an attempt to alter the bacterial microflora two open label prospective studies have been conducted with probiotics. One study contained 90 patients where Lactobacillus casei, Mesazaline or both were given for 15 days a month. Given separately, 76% was symptom free and the patients who received the combination became in 95% symptom free after 1 year.36 Another study compared an intestinal antimicrobial (dichlorchinolinol) and absorbent (active coal tablets) with the same set-up supplemented with non-pathogenic Escherichia coli in a prospective open trial in 15 patients administered for 1 and 5 weeks. The non-pathogenic E. coli significantly prolonged the symptomatic remission period (14 and 24 months).37

Diverticulitis

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Pathogenesis

Diverticulitis refers to a spectrum of diverticular disease ranging from subclinical inflammation to generalized peritonitis. The pathology of diverticulitis is characterized by inflammation and focal necrosis of diverticula leading to micro- or macroscopic perforation of a diverticulum. Most small perforations are walled off, although some will lead to abscess or fistula formation. The inciting agent of the inflammation was earlier thought to be fecoliths that obstructed diverticular lumens; this, however, turns out to be rare. The main culprit seems to be inspissated food that leads to mucus secretion and eventual bacterial overgrowth within the diverticulum.

Symptoms

The classic presentation of diverticulitis in the western world includes left lower quadrant abdominal pain and tenderness, constipation, fever and leucocytosis. However, the clinical features can be quite variable. Approximately 85% of diverticulitis involves the sigmoid/descending colon. Seventy percent of patients present with left lower quadrant pain and 25–50% of patients will report having had previous episodes of diverticulitis. Although constipation is present in 50% of patients, 25% to 35% of patients may present with diarrhoea, 20% to 62% may have nausea and vomiting and 10% to 15% may describe urinary symptoms.38 Abdominal tenderness is present in most patients, and approximately 20% will have a tender mass palpable on exam.8 Low-grade fever and leucocytosis are also characteristic, but 45% of patients will have a normal white blood cell count.39 The presentation is particularly apt to be atypical among patients with conditions such as HIV infection, organ transplantation or cancer, in which immunosuppression is common.40, 41

Not surprisingly, given the variable presentation of diverticulitis and the spatial relationship of the colon to other intra-abdominal organs, the differential diagnosis for diverticulitis is broad. Potential diagnostic considerations might include appendicitis, Crohn’s disease, colon cancer, ischaemic colitis, pseudomembranous colitis, complicated ulcer disease, ovarian cyst or torsion, or ectopic pregnancy. Nonetheless, the diagnosis is often relatively clear among those patients presenting with typical features.

Diagnosis

The diagnosis of diverticulitis is usually suggested by history and clinical exam. Various adjunctive tests, such as abdominal and chest x-ray, compression ultrasonography and single contrast barium enema have been and are used, although enema examinations are not much used anymore. Increasingly, computed tomography (CT) scans are the test of choice to confirm a clinical suspicion of diverticulitis. The literature has reported excellent test performance characteristics for CT scans, with sensitivity as high as 97% and specificity of up to 100%.42 Findings on CT scans include soft tissue density in pericolic fat (present in 98%), the presence of colonic diverticula (present in 84%), bowel wall thickening greater than 4 mm (present in 70%), phlegmon and pericolic fluid (present in 35%).43, 44 However, CT findings alone are insufficient to exclude cancer in approximately 10% of cases.45 Therefore, patients who have not had a colonoscopy yet should have one after resolution of the disease. CT has additional advantages of permitting classification into mild and severe categories, which may aid in predicting success of conservative therapy46 and in selecting patients for surgery.47, 48 Diverticulitis may be complicated by abscess and fistula formation, peritonitis, or obstruction. CT may help differentiate abscesses that require drainage versus those that can be managed conservative and that behave like uncomplicated diverticulitis; the suggested size cut-off for such a distinction is 5 cm, with smaller abscesses generally responding to medical treatment without drainage.

Treatment

The treatment of diverticulitis depends on the severity and extent of disease. Recommendations are available from some of the professional societies, such as the American College of Gastroenterology and the American Society of Colon and Rectal Surgeons. Many other countries conform themselves to these general guidelines with certain exceptions.

Patients (70% to 100%) with simple, uncomplicated diverticulitis will improve with conservative measures. Bed rest, only clear liquids or total dietary restriction are the first step. Antibiotics are usually, but not always given. A recent study questions the routine use of antibiotics.49 Antibiotics are generally chosen to cover Gram negative rods and anaerobes; for example a combination of ciprofloxacin and metronidazole.50–52 CT scans may be useful for predicting success of conservative therapy.48, 53 A critical decision is whether to hospitalise a patient; this decision may rest on such features as disease severity, ability to tolerate oral intake, age, comorbidity and availability of adequate support systems at home.

Complicated disease demands a more intense approach. One commonly used system to group patients according to severity of disease is the Hinchy classification54 (Table 2). Patients with abscesses larger than 5 cm usually require CT-guided abscess drainage. In cases of peritonitis (Hinchy 3 and 4) emergency surgery is required, where cleansing of the peritoneal cavity and a sigmoid resection with an end-to-end procedure is preferable. Peritonitis carries a high mortality rate of approximately 6% if purulent and 35% if faecal. Fistula will be electively operated, as will patients with obstruction where malignancy cannot be excluded with colonoscopy.

Table 2.   Hinchy classification of peritoneal contamination of diverticulitis
Stage 1Pericolic or mesenteric abscess
Stage 2Walled-off or pelvic abscess
Stage 3Generalized purulent peritonitis
Stage 4Generalized fecal peritonitis

Prognosis

The prognosis of diverticulitis after resolution of the acute symptoms is generally good. Approximately 30% to 40% of patients will remain asymptomatic, 30% to 40% will have episodic cramps without clinical evidence of recurrent diverticulitis and 30% will have recurrent diverticulitis.8, 10, 12, 51 In the past, Parks stated that recurrent attacks of diverticulitis had a high likelihood of being complicated and to be associated with higher mortality than initial attacks.8 Furthermore, guidelines for elective surgery to prevent recurrent attacks were derived from the Parks study and newer studies were not included in these guidelines yet.55 The older studies did not account for better medical care and new therapeutic options like CT-drainage. However, more recently it appears that recurrent attacks occur less frequently and with similar likelihood of complications as initial attacks.10, 55, 56 Moreover, only about 25% of people with complicated diverticulitis have a previous attack, thus making prevention even more difficult.57–59 Among patients who undergo surgery for diverticulitis, 15% will develop diverticula in the remaining colon,60 approximately 2% to 11% will need further surgery,60, 61 and up to 27% will have post-operative pain in the same location.

Elective surgery for whom?

Indications for elective surgery remain controversial, particularly for uncomplicated diverticulitis. In view of the recent literature, a more nuancated approach may be appropriate. It seems that some subgroups are at risk for complicated disease. These are the patients with co-morbidity, like diabetes mellitus, collagenous disease and the immune compromised.55, 60, 61 Also the concept that younger (male) patients are at high risk for complicated (recurrent) diverticular disease merits more critical re-appraisal. Older studies suggested indeed a higher risk in these patients,27, 51, 62–65 but newer studies have shown that establishing the correct diagnosis was delayed because it was not suspected. Moreover, there was a striking percentage of obesitas masking the symptoms in these patients.66 The recurrence and complication rate were not higher then in elderly patients.67–74 Adipositas itself forms a risk factor for diverticulitis. They have not only an increased risk to develop diverticulitis,66 but also experience more complications.75 Obese patients have an increased mortality rate of 5.276 and require a longer operation time and more post-operative analgesics.77 Thus suggested by some authors resection after two or three episodes of uncomplicated diverticulitis therefore needs to be re-considered and should be limited to patients at risk with co-morbity like diabetes, collagenous disease and the immune compromised patient.

New issues

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Segmental colitis associated diverticulitis

This is defined as chronic mucosal inflammation of the sigmoid colon bearing diverticula with rectal spearing. The clinical presentation consists of rectal bleeding, occasionally left-sided abdominal pain and less frequently, bowel alterations. The endoscopic features are those of sigmoiditis (erythema, congestion and contact bleeding) with rectal sparing. The orifices of diverticula may or may not be involved. The histological changes78 are mostly similar to those detectable in inflammatory bowel disease (IBD): cryptic abscesses with crypt distortion, mononuclear cell infiltrate, lymphoid aggregation, epithelial cell sloughing79 and sometimes granulomata.80, 81 On the whole, the histopathological features and rectal sparing mimic the picture of Crohn’s disease rather than that of ulcerative colitis. In fact, in ulcerative colitis even when the rectum is endoscopically spared, histological involvement is always present.82

Is segmental colitis a distinct clinical entity or coexistence of sigmoid diverticulosis and IBD? Both diverticulosis and segmental colitis usually affect elderly patients, especially men. It is also known that IBD presents a second peak of incidence in the population over the age of 60.83 The incidence of segmental colitis is estimated to be 0.3–3.8%.80, 84–86 The results above are too small to allow definitive conclusions to be made in terms of epidemiology.

To add to the confusion, in about 10% of cases of segmental colitis, inflammation subsequently spreads to the rectum, even when this was initially histological normal, making it impossible to distinguish this condition from ulcerative colitis.80, 84 On the other hand, even when the rectum remains uninvolved and concomitant Crohn’s colitis can be suspected, perianal disease is always absent.80, 87 In segmental colitis, unlike in Crohn’s colitis, symptoms such as nausea, vomiting, weight loss and fever are never present and laboratory findings are usually normal, the acute-phase reactants and/or white cell count are rarely increased.85, 87 When segmental colitis is considered a distinct disorder, what are the possible causes of local inflammation? A role for bacterial flora promoted by faecal stasis has been postulated.87, 88 Other postulated factors are increased permeability to intraluminal antigens,87 focal ischaemia due to impairment of local microcirculation89 and enhanced local production of nitric oxide and oxygen-reactive radicals.87

Medical treatment of segmental colitis is empirical and usually carried out, in addition to a high-fibre diet, by the same pharmacological agents employed in the treatment of IBD, i.e. sulfasalazine, Mesazaline and occasionally antibiotics.79, 84 The majority of cases are responsive to such medications,79, 84, 90 immunosuppressive medication is rarely required. Again, this differs from IBD in which steroids and immunosuppressants are often necessary. Patients with segmental colitis rarely require surgery79, 89 and in contrary to patients with Crohn’s colitis, they seldom experience post-operative recurrences.81, 91

A differential diagnosis with IBD is important in order to optimise the treatment and long-term management of the disease. To that purpose the diagnostic workout should include accurate evaluation of the small bowel by means of ileocolonoscopy with mucosal biopsies, and or other imaging techniques.

Diverticular disease and cancer

Some studies have suggested the relationship between diverticulitis and colon cancer. In 1979 an association in 42 patients with diverticulitis in a group of 385 cases of colonic cancer was found.92 In a retrospective study of a group of 150 patients in 1988 and 630 patients in 2002, there was a higher incidence of advanced adenomas in the sigmoid colon in patients with diverticular disease. Nevertheless, there was no higher prevalence of colorectal cancer in patients with diverticula in comparison to those without.93, 94

In a study with 7159 patients, a significantly long-term increased risk of left-sided colon cancer in patients with diverticulitis compared to those with only diverticulosis was found.95 In contrast, a study with 512 patients with colonic resection due to diverticulitis showed a statistically significant decreased rate of advanced colonic neoplastic lesion in all age groups, but no relation with adenocarcinoma.96

Laboratory tests are contradictory. A study in patients with diverticular disease demonstrated that hyperproliferation of the colonic mucosa was localized in the upper third of the colonic crypts.97 This hyperproliferation of the colonic mucosa was detectable in the whole length of the colonic crypts in the patients not only with symptomatic diverticulosis and acute diverticulitis but also in patients with asymptomatic diverticulosis.98 This suggests that not only patients with acute diverticulitis but also those with asymptomatic diverticulosis may be at a risk of developing adenomas and colonic carcinomas. In contrast, a different matrix micro environment was found between the colonic tissue architecture of the patients with colon cancer and those with diverticular disease, thus implying no predisposition for cancer in diverticular disease.99 Although this is different from overt diverticulitis.

One of the feasible explanations for the association between diverticular disease and colorectal cancer is that the presence of an inflammation process increases the risk for a malignant transformation,100 as in the Western population diverticular disease occurs usually in the left colon.

Conclusions

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References

Diverticulosis and diverticulitis are emerging diseases. Prevention is an important factor and therefore a fibre enriched diet should be encouraged. When diverticulitis develops, uncomplicated disease can be managed conservatively. Even abscesses smaller than 5 cm can be managed with bed rest, dietary restrictions and antibiotics. Larger abscesses are punctured under CT guidance. The more serious complications require emergency surgery. New insights have shown that elective surgery to prevent recurrence should be reserved for patients at risk (co-morbidly, e.g. immune compromised). Not youth, but obesity is a risk factor for complicated disease. New therapies like mesazaline, rifaximin and probiotics merit more attention in prevention of diverticular disease and diverticulitis. The relationship of diverticular disease with inflammatory bowel disease (segmental colitis associated with diverticulities) and sigmoid carcinoma needs further evaluation.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Diverticulosis
  5. Diverticular disease
  6. Diverticulitis
  7. New issues
  8. Conclusions
  9. References
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