Colonic diverticular disease

Abstract

Diverticula are outpouchings of the intestinal wall and are common anatomical alterations detected in the human colon. Colonic diverticulosis (the presence of diverticula in the colon; referred to as diverticulosis) remains asymptomatic in most individuals but ~25% of individuals will develop symptomatic diverticulosis, termed colonic diverticular disease (also known as diverticular disease). Diverticular disease can range in severity from symptomatic uncomplicated diverticular disease (SUDD) to symptomatic disease with complications such as acute diverticulitis or diverticular haemorrhage. Since the early 2000s, a greater understanding of the pathophysiology of diverticulosis and diverticular disease, which encompasses genetic alterations, chronic low-grade inflammation and gut dysbiosis, has led to improvements in diagnosis and management. Diagnosis of diverticular disease relies on imaging approaches, such as ultrasonography, CT and MRI, as biomarkers alone are insufficient to establish a diagnosis despite their role in determining disease severity and progression as well as in differential diagnosis. Treatments for diverticular disease include dietary fibre, pharmacological treatments such as antibiotics (rifaximin), anti-inflammatory drugs (mesalazine) and probiotics, alone or in combination, and eventually surgery. Despite being effective in treating primary disease, their effectiveness in primary and secondary prevention of complications is still uncertain.

Figure 1.. Diverticulosis and diverticular disease.

a| Diverticulosis can occur in any part of the colon. However, in western countries it generally occurs in the left (descending and sigmoid) colon involving the mucosa and submucosa, whereas in eastern countries protrusion generally occurs in the right colon (ascending)involving all colonic layers. Faecal stasis and faecal impaction in the diverticulum might lead to gut dysbiosis, resulting in the development of symptoms (symptomatic uncomplicated diverticular disease; SUDD) and, sometimes, macroscopic evidence of diverticular inflammation (acute diverticulitis). Diverticular haemorrhage might also occur and is more commonly observed in eastern than in western populations. b |SUDD is characterized by absence of macroscopic evidence of inflammation (left panel), but histology often shows patchy lymphoplasmacytic inflammation with lymphoid follicles that expand the lamina propria (arrow; right). Magnification 40×. c | Sometimes patients have persisting abdominal pain following acute diverticulitis, a clinical situation called post-diverticulitis SUDD. In these patients, endoscopy may not show signs of inflammation (left panel), and inflammation is generally located at the bottom of colonic crypt by histology (circled, right panel). Magnification 10×. d | Diverticular inflammation in acute diverticulitis can be observed at endoscopy (left panel), and acute and chronic inflammatory infiltrate, as well as cryptitis (thick white arrow; right panel) by histology. Magnification 100×. All histological images are haematoxylin and eosin staining of paraffin-fixed samples. Histological images kindly provided by Dr. C. D. Inchingolo (Andria, Italy) and Professor M. Walker (Newcastle, Australia).

Figure 2.. Proposed biological mechanisms for diverticular disease.

a | Diverticulosis is hypothesized to be the result of neuromuscular abnormalities such as alterations in collagen and the enteric nervous system, in the setting of increased intraluminal pressure. b | Symptomatic uncomplicated diverticular disease (SUDD) can arise from an altered intestinal microbiota leading to chronic, low-grade inflammation mediated by tachykinins. Increased nerve sprouting lead to subsequent visceral hypersensitivity. c | Alterations in the intestinal microbiota leading to mucosal barrier dysfunction and inflammation and/or local trauma from a faecalith are proposed mechanisms for diverticulitis. d | Diverticular hemorrhage occurs at sites of asymmetrical vascular thickening. Risk factors for vascular injury such as obesity and hypertension and luminal trauma contribute to bleeding.

Figure 3.. Cross–sectional imaging of diverticulosis and diverticular disease.

Colonic diverticulosis can be clearly visualized using ultrasonography (panel a), CT (panel b) and MRI (panel c). Absence of pericolonic involvement (namely absence of thickening of the diverticular wall and absence of involvement of pericolic fat) is indicative of a lack of inflammation (Transversal section of sigmoid colon characterised by thickened muscularis propria (mp), with a divericulum appearing as hyperechoic lesion (arrow) with posterior hypoechoic halo; panel a). Ultrasonography can also very useful in detecting acute inflammation of diverticula (Transversal section of sigmoid colon characterised by thickened muscularis propria, with an inflammed divericulum appearing as hypoechoic protrusion (arrow) surrounded by hyerpoechoic mesenteric tissue; panel d). CT can reveal thickening of diverticular wall with inflammation of the pericolonic fat (the so-called fat stranding, white arrow, panel e), and MRI can show also diverticular inflammation (thin white arrow, panel f). Images in panel a and panel d are provided by Professor G. Maconi (Milan, Italy); images in panel b, c, e and f are provided by Dr. M. Maiorano (Andria, Italy).

Figure 4.. The DICA classification system.

The Diverticular Inflammation and Complication Assessment (DICA) classification is the first endoscopic classification developed specifically to describe objectively the presence of diverticulosis in the colon and signs of current or past diverticular inflammation. This classification consists of four main colonic characteristics (the location of diverticulosis, the number of diverticula in each colonic segment, the presence or absence of inflammation, including SCAD, and the presence or absence of complications). Subfeatures are considered and scored. If two different grades of severity are detected at the same time (for example, some diverticula with hyperaemia and others showing erosions), the more severe grade of inflammation (for example, erosions instead of hyperaemia) must be scored and the sum of the scores leads to three different DICA scores: DICA1, DICA 2, and DICA 3.

Figure 5.. Clinical presentations of acute diverticulitis.

The clinical presentation of diverticulitis, in which diverticula become inflamed or infected, depends on the location of the affected diverticulum, the severity of the inflammatory process, and the presence of complications. Colonic diverticula have narrow necks that can be easily obstructed by fecal matter. Obstruction of the neck initiates a cascade of events that might lead to distention of the sac, bacterial overgrowth, vascular compromise, and perforation (that is, a hole in the wall of the large bowel). Most perforations are localized and contained, so that uncomplicated diverticulitis is present as small localized pericolic abscess. Complicated diverticulitis usually results from worsening of the infection. If this is the case, large perforations develop with consequent mesenteric abscesses, free perforation and fecal peritonitis. This decription, which classifies acute diverticulitis in four stages, was first developed by Hinchey et al. Fistulas and obstruction might suddenly develop during an episode of diverticulitis or can be a late complication. Diverticular haemorrhage, however, represents a non-infective complication.

Figure 6.. Algorithm for the management of acute uncomplicated diverticulitis.

The clinical suspicion of acute diverticulitis needs to be confirmed by imaging (US and/or CT scan) and laboratory parameters (leukocyte count, erythrocyte sediment rate and CRP, which correlates with the severity of the disease). In the setting of acute uncomplicated diverticulitis, normal WBC and low PCR (together with absence of fever) characterize patients as low-risk, in whom outpatient treatment is feasible and omission of antimicrobial therapy is safe. Besides comorbidities, immunosuppression and the availability of outpatient support need to be taken into account. Outpatients should be treated with a clear (low-fibre) liquid diet and antimicrobials should only be given in selected cases. For patients needing admission, intravenous fluids and intravenous antimicrobials should be administered. In both low-risk and high-risk patients, improvement of symptoms is expected within 2–3 daysand then, normal diet can be resumed. If improvement continues, patients might be discharged to complete a 7–10-day antibiotic course at home, if deemed necessary. Failure of conservative medical treatment warrants a diligent search for complications, consideration of alternative diagnoses and surgical consultation.

Figure 7.. Management of acute complicated diverticulitis.

Evaluation and treatment approach of complicated disease depends on the severity of presentation, presence of complications (peritonitis, abscess), and comorbid conditions. Abdominal CT scan is very useful to diagnose diverticular complications according to the Hinchey classification. Patients with small abscesses are usually manage by antimicrobial drugs and liquid diet. If antimicrobial therapy is ineffective, larger abscesses need to be treated by percutaneous drainage, which can allow subsequent elective surgery. In addition to medical treatment, in case of diffuse peritonitis, resection surgery is mandatory. The most suitable surgical approach needs to be selected on a case-by-case basis, according to individual factors such as the extent of the inflammation in the area of the proposed anastomosis and patient stability and comorbidity. Modified from Ref#22 ^aRecommended by current guidelines, but some evidence to suggest good outcomes without resection in selected patients

Figure 8.. Current and future predictors of outcome in diverticular disease.

Predictors of outcome in diverticular disease have been identified, including family history, imaging characteristics (such as length of the involved colon, or retroperitoneal abscesses) and laboratory parameters (raised fecal calprotectin during the follow up). Future predictors include endoscopic characteristics of the affected colon, according to the Diverticular Inflammation and Complication Assessment (DICA) classification. Other future predictors, which need further studies to confirm the preliminary results, are the identification of changes in the colonic microbiota and in the faecal and urinary metabolomes in patients with diverticular disease. These predictors might hopefully help to identify patients with diverticulosis, who will develop diverticular disease.