Abstract
By the age of 50 years, 50% of the population will have diverticula of the large bowel. Ten to 20% will experience a clinically significant complication, principally diverticulitis and haemorrhage. As the elderly population grows, a concomitant rise in these patients will occur. Early diagnosis including the recognition of complications is key in reducing morbidity and mortality.
The GP curriculum and diverticular disease
Explain the indications for urgent referral to specialist services, especially for patients with suspected gastrointestinal (GI) cancer Give basic dietary advice Provide emergency care including the ability to recognize an acute abdomen and intervene appropriately Understand secondary care management of digestive problems, including surgical options
Terminology
A diverticulum is a sack-like protrusion of mucosa through the muscle layer of a hollow or fluid-filled organ. A true diverticulum consists of all three tissue layers including mucosa, submucosa and muscular layers. Colonic diverticula are really pseudodiverticula consisting of only the mucosa and submucosa covered by serosa.
Diverticulosis refers to the presence of diverticula within the colon, which are asymptomatic. Diverticular disease is used to describe the full spectrum of symptoms as a consequence of having diverticula (including pain, bloating and a change in bowel habit) but in the absence of inflammation.
Acute diverticulitis is the most common complication affecting 10–25% of people with diverticulosis. Diverticulitis therefore refers to the presence of peridiverticular inflammation and infection. This term represents a spectrum of inflammatory changes, ranging from subclinical local inflammation to generalized peritonitis with free perforation. The clinical manifestation depends on the size of perforation and how well it is walled off by surrounding pericolic structures, particularly fat and mesentery.
The severity of acute diverticulitis can be further classified by the Hinchey system (described below). Complicated diverticulitis is the term used to describe diverticulitis accompanied by abscess formation, fistulae, stricture/obstruction and/or perforation (the rupture of a peridiverticular abscess into the peritoneal cavity, causing either purulent or faecal peritonitis).
Epidemiology
In Western society, the prevalence of diverticulosis increases uniformly with age. It affects 50% of people by the age of 50 years, 67% by the age of 80 years and has a similar preponderance in both sexes. Of these patients, 75% will remain asymptomatic and the condition is often diagnosed incidentally following colonic investigation, usually for bowel cancer. Of the 25% who develop symptoms, three quarters will develop diverticulitis and the remainder will experience diverticular haemorrhage. A third of those who have a diverticular haemorrhage will experience severe haemorrhage requiring transfusion, admission to the intensive care unit and/or laparotomy.
Diverticular disease is uncommon among those aged younger than 40 years, occurring more frequently in males with obesity (a significant risk factor). Between 2 and 5% of all episodes of acute diverticulitis occur in this age group. In younger patients, diverticular disease is associated with a more aggressive clinical course which frequently requires surgical intervention.
Relevant anatomy
Distal to the caecum, the colon is divided anatomically into ascending, transverse, descending and sigmoid segments. Histologically they are indistinguishable from one another. The normal colonic wall consists of mucosa (epithelium, lamina propria and muscularis mucosae), submucosa (loose collagenous tissue supporting the mucosa containing neurovascular structures) and the muscularis propria (smooth muscle layer arranged in an inner circular layer and outer longitudinal layer). In the large intestine, the outer longitudinal layer of smooth muscle is concentrated mainly in three narrow bands known as taeniae coli. The muscle layer becomes progressively thicker in the more distal colon, particularly the sigmoid colon. The taeniae eventually fuse in the proximal rectum producing a useful landmark for identifying the distal extent of resection when performing a sigmoid colectomy. Diverticula can occur throughout the colon but are most common near the descending and sigmoid colon in the Western world. The sigmoid colon is the segment of the colon with the smallest diameter and is involved in 95% of cases.
Pathophysiology
Diverticulosis
Diverticula occur at points of relative weakness in the muscularis layer, where intramural branches (vasa recta) of the marginal artery penetrate the colonic wall. Theories underlying the development of diverticula focus on three areas:
Colonic wall abnormalities Colonic motility Dietary factors and the role of fibre
Patients with diverticulosis tend to have a thicker muscular wall layer due to a phenomenon known as mycosis, whereby thickening of the circular muscle layer and shortening of the taeniae result in luminal narrowing. There is also an increase in elastin deposition resulting in contraction of the taeniae coli. The sigmoid is the narrowest portion of the entire colon. These processes together result in elevated intraluminal pressures and combined with age-related changes in collagen composition weaken the colonic wall, predisposing to the formation of diverticula.
Although, under normal circumstances, the pressure throughout the colon should be equal, segmentation (a motility process in which segmental muscular contractions separate the lumen into chambers) is exaggerated in diverticulosis, occluding both ends of the chamber during muscular contraction, raising the pressure and predisposing to herniation of the mucosa.
A large body of evidence based on population studies implicates lack of dietary fibre in the pathogenesis of diverticulosis. Low dietary fibre decreases stool bulk and prolongs transit times, causing higher intraluminal pressures. The role of fibre is not only supported by the low prevalence of diverticular disease in high-fibre-consuming populations but also by animal studies. Studies in rats have shown that diverticula develop in 45% of animals on a chronic low-fibre diet, opposed to only 9% of rats on a high-fibre diet.
Acute diverticulitis
Compacted matter (a faecolith) can cause obstruction at the neck of a diverticulum that promotes mucus hypersecretion and bacterial proliferation, leading to erosion of the purely mucosal structure. If the blood supply to a diverticulum is mechanically compromised, microperforations can result, causing peridiverticular inflammation and abscess formation. The Hinchey classification is used to grade the extent of inflammation and can be used as a guide when making decisions regarding patients who may require surgical intervention. The Hinchey system is summarized in Box 1.
Hinchey classification
Stage I—Small or confined pericolic or mesenteric abscess
Stage II — Large abscess, often confined to the pelvis Stage III — Perforation causing generalized purulent peritonitis
Stage IV — Faecal peritonitis
Most perforations are small and contained within pericolic fat, resulting in a small pericolic abscess (Stage I disease). Larger abscesses (Stage II) may rupture into the peritoneal cavity (Stage III). Progression to gross faecal peritonitis (Stage IV) depends on whether the faecolith continues to obstruct the diverticulum.
Clinical assessment in primary care
Diverticular disease
The symptoms of diverticular disease can be non-specific. Pain may be colicky in nature, localized to the left of the abdomen and may be exacerbated by eating and relieved by passing flatus or defecation. Change in bowel habit can occur, with constipation (infrequent bowel actions and hard stool) occurring more frequently than diarrhoea and associated bloating and flatulence. Patients may also describe a change in the calibre of their motion, some reporting a narrower stool. Appetite and weight should remain normal. Differentials that should be considered are listed in Box 2.
Differential diagnoses of diverticular disease
Colorectal cancer Functional constipation — poor diet, poor fluid intake, sedentary lifestyle Constipation-prominent irritable bowel syndrome Painful rectal conditions, e.g. anal fissure Drug related, e.g. opioids Peptic ulcer disease
On examination, the patient should appear systemically well. There may be some fullness or tenderness in the left lower quadrant of the abdomen but there should be no peritoneal signs or frank peritonitis. Rectal examination should be performed to assess for stool consistency, bleeding and any masses.
Diverticular disease can present with rectal bleeding and accounts for 30–50% of all cases of massive lower GI blood loss. It is estimated that 15% of patients with diverticulosis will experience large volume bleeding at some point in their lives. Colorectal cancer is another common cause of lower GI bleeding but produces frequent, small or continual bleeds, symptoms that are unlikely to be caused by diverticular disease. In addition, bleeding from a cancer is unlikely to result in the passage of clots; however, clots are very common in bleeding from diverticula. Angiodysplasia can present with a similar pattern of bleeding and after diverticulosis, it is the second leading course of lower GI blood loss.
Bleeding from the bowel not obviously caused by haemorrhoids or anal fissure always requires investigation to exclude other more sinister causes, even if the patient is known to have diverticular disease. Patients should always be assessed for the presence of red flag symptoms, which are listed in Box 3. In addition, a positive faecal occult blood test should never be attributed to colonic diverticular disease alone.
Acute diverticulitis
Patients with simple diverticulitis typically present with a short history (several days) of left-sided abdominal pain.
Red flag symptoms
Weight loss Tenesmus Rectal bleeding for longer than 4 weeks Altered bowel habit for longer than 6 weeks Palpable abdominal mass Positive faecal occult test Iron deficiency anaemia Family history of bowel cancer or inflammatory bowel disease
Left lower quadrant pain occurs in the majority of patients and it may extend across the suprapubic region and into the right lower quadrant. Right-sided pain may occur in the presence of right-sided diverticulosis, as well as in those who have a redundant sigmoid colon lying on the right side of the abdomen. In these patients, acute diverticulitis can be confused with acute appendicitis and they will go on to have a diagnostic laparoscopy. Pain may be associated with anorexia, nausea, vomiting and change in bowel habit. The presence of lower urinary tract symptoms, such as dysuria, frequency and urgency, herald more serious problems and often indicate a pelvic abscess or colovesical fistula. Box 4 summarizes the signs and symptoms of acute diverticulitis.
Features of acute diverticulitis
Acute left lower quadrant pain (93–100%) Fever (57–100%) Leucocytosis (69–83%) Nausea and vomiting Mass Constipation Diarrhoea Urinary symptoms
Patients may present with a complication of diverticulitis. A history of recurrent lower urinary tract infections and the presence of pneumaturia or faecaluria indicates the presence of a colovesical fistula.
On examination, there may be a low-grade fever, tachycardia and hypotension. Hypotension may be secondary to dehydration (look for reduced skin turgor and dry mucous membranes) or septic shock. Focal tenderness in the left lower quadrant (with or without guarding) may be associated with a palpable inflammatory mass. Rectal examination may reveal tenderness or a mass, which could indicate an associated low-lying pelvic abscess. There are no pathognomic signs of acute diverticulitis, hence a range of differentials (listed in Box 5) should be considered in the assessment of the patient presenting with these symptoms.
Marked rebound tenderness, guarding and hypoactive or absent bowel sounds indicate significant peritoneal inflammation. Board-like rigidity due to contraction of the abdominal wall muscles will be felt in generalized peritonitis.
Differential diagnoses of acute diverticulitis
Colorectal cancer Sigmoid volvulus Gastroenteritis Irritable bowel syndrome Bowel obstruction Ischaemic colitis Crohn's colitis Appendicitis
Pelvic inflammatory disease Ruptured ovarian cyst Ovarian torsion Ectopic pregnancy
Lower urinary tract infection Pyelonephritis
An important surgical emergency to consider is volvulus affecting the sigmoid colon. Similarly, this will present with colicky left lower abdominal pain, with associated distension, and absolute constipation, which may be associated with nausea. Vomiting is usually a very late sign. Fever may occur, especially if the bowel becomes ischaemic and there is associated perforation.
Management in primary care
Diverticular disease
Treatment options in patients with symptomatic diverticulosis surround optimizing symptom control. Dietary recommendations specifically revolve around encouraging a high-fibre diet. The goal is to reduce intestinal spasm by increasing bulk within the intestine, which is achieved by maintaining a high-fibre diet and drinking sufficient quantities of fluid. In general, the diet should be balanced and contain whole grains, fruits and vegetables. As well as promoting general health, this also reduces the risk of developing diverticular disease. Patients should increase fibre intake gradually (to minimize flatulence and bloating) and a high-fibre diet should be maintained for life. Patients should be advised to consume between 18 and 30 g of fibre per day (this equates to approximately two bowls of bran breakfast cereal). Eating five portions of fruit or vegetables a day will contribute to half of the daily recommended fibre intake.
Patients who experience difficult symptoms despite dietary changes may benefit from the use of fibre-bulking agents. If pain and bloating are a particular problem, a trial of antispasmodics or peppermint oil can be initiated.
Time should be taken to explain that it can take up to 3 weeks before a change in symptoms is noticed. Those who are overweight should be offered advice to reduce weight. Additionally, those who smoke should be offered access to smoking cessation services. Complicated diverticular disease has been noted with increased frequency in patients who smoke, those who are obese and have low-fibre diets. Smoking is thought to have an immunosuppressive effect on the colonic mucosa, which increases the likelihood of developing acute exacerbations that in turn can lead to more complicated presentations of acute diverticulitis.
Acute diverticulitis
Uncomplicated diverticulitis can be successfully managed by GPs. Those with mild abdominal symptoms in the absence of high-grade fever (above 38°C), excessive vomiting or marked peritoneal irritation can be managed in the primary care setting, as long as there is opportunity for follow-up.
Patients should be prescribed broad-spectrum antibiotics to cover anaerobes and Gram-negative rods (in particular Escherichia coli and Bacteroides fragilis). Suitable choices include co-amoxiclav or a combination of ciprofloxacin and metronidazole (if the person is allergic to penicillin) and treatment should last for at least 7 days. Simple analgesia such as paracetamol should be recommended. Non-steroidal anti-inflammatory drugs (NSAIDs) have been the most consistently identified risk factor for diverticular perforation. They are also an important precipitating factor in flare-ups of diverticular disease. Risk-benefit analysis needs to be considered when prescribing NSAIDs in any patient known to have diverticular disease.
Initially, patients should be advised to consume clear liquids only. A gradual introduction of a low-residue diet can begin once there is evidence of symptomatic improvement. Clinical review should take place within 48 hours. Conservative treatment will resolve acute diverticulitis in 85% of patients. If there is no improvement at this stage, referral to secondary care should be discussed with the nearest surgical care unit. The indications for referral to hospital are summarized in Box 6. The patient should be advised to seek help if symptoms cannot be controlled with over-the-counter analgesics.
Referral to secondary care
Inadequate pain relief with simple analgesia Poor oral intake causing any degree of dehydration and poor tolerance of oral antibiotics Frail elderly or significant co-morbidities Past history of complicated diverticulitis Signs of complicated diverticulitis, e.g. generalized peritonitis Symptoms that persist after 48 hours despite conservative management at home Immunocompromised patients, e.g. long-term steroid use, human immunodeficiency virus/adult immune deficiency syndrome
Follow-up
Due to the risk of perforation, endoscopic evaluation is contraindicated in acute diverticulitis. Colonoscopy or flexible sigmoidoscopy with barium enema (Fig. 1) is indicated 6–8 weeks after the resolution of the initial attack to evaluate the colon. This is performed to confirm the diagnoses and crucially to rule out an underlying malignancy of the colon. As these patients will have a reduced luminal calibre, endoscopy can be unsuccessful. Therefore, computed tomography (CT) colonography is frequently employed.
X-ray following barium enema demonstrating colon diverticula.
Investigation and management in secondary care
Initial investigations should include urinalysis, blood tests (full blood count, urea and electrolytes, C-reactive protein, group and save sample so blood can be quickly cross matched if operative intervention is required), and plain chest and abdominal radiographs.
A leucocytosis is commonly seen in diverticulitis and would support the presence of an inflammatory process. Urea and electrolyte monitoring will guide fluid replacement therapy. A quarter of those with a perforation will have free gas under the diaphragm on chest X-ray. A plain abdominal X-ray may demonstrate a pneumoperitoneum, the signs of which include Rigler's sign, in which both sides of the bowel are outlined by gas. Thickening of the bowel wall may also be seen due to oedema of the wall. Abnormal abdominal X-rays are found in 30–50% of patients with acute diverticulitis. The most common findings include small and large bowel dilatation or ileus, bowel obstruction or soft tissue densities suggestive of abscesses.
People with diverticulitis often have sufficient signs and symptoms to allow an empirical diagnosis and initiation of treatment. In the absence of generalized peritonitis, non-operative management is always preferred. In hospital, management includes a short period of bowel rest with the use of intravenous antibiotics and fluids. Antibiotics are switched to an oral form when the patient is afebrile, reports improving symptoms, is tolerating oral intake and has decreasing inflammatory markers (generally within 24–48 hours).
Complicated diverticulitis
If, despite 48–72 hours of antibiotics, the patient remains pyrexial with symptoms that are unchanged or worsening, or with an enlarging lower abdominal mass, further imaging is usually considered. Although ultrasound scanning can demonstrate abscesses (which may be amenable to ultrasound guided percutaneous drainage), CT is considered the most sensitive and specific modality. CT is not only the most sensitive method of evaluating and defining the extent and severity of inflammatory processes (including monitoring of inflammatory activity) but will also identify the presence of additional pathologies, although there is frequently diagnostic confusion between sigmoid perforations due to cancer and those due to diverticulitis.
Approximately 15% of patients develop pericolonic or intramesenteric abscess. Those smaller than 5 cm in diameter will usually resolve with antibiotic treatment without any further intervention but larger abscesses may require percutaneous drainage.
Fistulae (ureteric, colovesical, colovaginal or colocutaneous) can occur in patients with complicated diverticular disease. They are produced when an abscess spontaneously decompresses by perforating into an adjacent viscus or through the skin.
Bowel obstruction (complete colonic obstruction) is rare and accounts for 10% of all cases of large bowel obstruction. Partial obstruction is more common and may result from a combination of colonic/pericolonic oedema, bowel spasm, compression from an abscess and chronic inflammatory changes.
Surgical management
Emergency
The majority of patients admitted with acute diverticulitis will respond to conservative management but 15–30% will require a laparotomy during their stay in hospital. Most patients coming to laparotomy in the UK have Hinchey 3 or 4 disease. Indications for emergency surgery (see Box 7) include generalized peritonitis, usually related to free perforation of a diverticulum with faecal peritonitis, or rupture of a pericolic abscess causing purulent peritonitis. Free perforation, although uncommon, carries a high mortality rate of 35% and requires urgent intervention.
Indications for surgery
Diffuse peritonitis Persistent sepsis despite antibiotic therapy and percutaneous drainage Bowel obstruction Fistula Inability to exclude carcinoma from CT imaging
As for all patients undergoing a major emergency surgical procedure, the main priority at this stage is adequate preparation and resuscitation. Fluid replacement should be accurately calculated and administered with care, as many of these patients will be elderly with a poor myocardial reserve. Preoperative full blood count, urea and electrolytes, liver function and clotting results are essential. It is of critical importance that a senior member of the surgical team is available to discuss the potential risks and benefits of surgery with patients before they are moved down to the operating theatre. In these stressful circumstances, it is imperative to contact the next of kin (with the permission of the patient).
The surgical options will depend on the current physiological status of the patient, preoperative morbidity and the degree of intra-abdominal contamination. The preferred operation is one where the diseased segment of colon is resected and a primary anastomosis is created between the proximal and distal margins of bowel (with or without a temporary diverting/covering ileostomy). This method is predominantly used in centres that deal with diverticular disease electively. The most common procedure performed, however, is a Hartmann's procedure, which is the mainstay of surgical treatment for perforated diverticular disease. This involves complete excision of the sigmoid colon, closure of the rectal stump and the formation of a colostomy. Hartmann's procedure is used in the setting of significant peritoneal contamination or when a patient is clinically unstable. In this situation, the risks of performing a primary anastomosis would be significant and the potential for an anastomotic leak would be very high. A Hartmann's procedure can be reversed at a later date by anastomosing the descending colon (colostomy) to the rectal stump. However, only 50% of Hartmann's procedures ever get reversed because the population undergoing surgery is frequently elderly with other co-morbidities.
Post-operative care
Depending on the patient's condition and any perioperative events, it is likely that he or she will be transferred to an intensive care or high dependency unit. Key features of management at this stage are optimal pain control, continued circulatory support with intravenous fluids and minimizing post-operative complications, such as hospital acquired pneumonias, by working with other health care professionals such as physiotherapists. A slow introduction of oral intake will commence when the surgical team feel it is appropriate. As the majority of these patients will have had some form of stoma created, it is imperative at this stage that they are introduced to specialist colorectal nurses. The education and training patients receive will enable many of them to rapidly become able to care for their stomas independently.
Elective surgery
The decision to proceed to elective colectomy after recovery from uncomplicated acute diverticulitis is made on a case-by-case basis. One-third of patients with an initial episode of diverticulitis will go on to have a second episode. After the second attack, another third of these patients will have a further episode. The number of episodes of uncomplicated diverticulitis does not necessarily determine whether surgery is appropriate because studies have shown that elective surgery following uncomplicated episodes might not decrease the likelihood of later emergency surgery or overall mortality. Generally, patients being considered for surgery need to be in good health and should have had at least two severe episodes needing hospitalization. Younger patients (under the age of 50 years) are considered at an earlier stage because of the greater lifetime risk of complications and the lower risks associated with surgery. Elective surgery is considered in all patients with disease complicated by fistula to the bladder, vagina or skin unless extremely unfit.
Key points
With an increasing elderly population, more patients are presenting with diverticular disease and its complications Dietary modification alongside fibre-bulking agents is commonly used in the management of symptoms Acute diverticulitis can be managed in the primary care setting (as long as there is sufficient opportunity for follow-up) with broad-spectrum antibiotics and appropriate advice to ensure a short period of bowel rest A thorough physical examination is critical in suspected diverticulitis, to identify those patients who may require hospitalization