19th July 2023

Diseases of the Large Bowel

This section focuses on diseases that predominantly affect the large bowel aka the colon. The colon is the main site of water reabsorption and uses peristaltic and high amplitude propagating contractions to move its contents along the tract and eventually result in defecation. Disease within this part of the GI tract results in symptoms including change in stool form and/or frequency, abdominal pain and PR bleeding. Please note:

• Some of the common large bowel diseases, including infective gastroenteritis and inflammatory bowel disease, will be covered in the topic “Infection and Inflammation”.
• Ischaemic bowel diseases, which affect both the small and large bowel, will be combined and only covered in this section to avoid duplication.

Colorectal Cancer (CRC)

CRC is the 3rd most common cancer in the Western world. The most common histology type is adenocarcinoma. Risk factors include increasing age, male gender, Caucasian or Black ethnicity, family history, obesity, physical inactivity and high red meat consumption. Symptoms depend on the site of the tumour but include abdominal pain, PR bleeding and change in bowel habit. Signs include an unexplained iron deficiency anaemia, palpable abdominal or rectal masses and evidence of weight loss. The gold standard investigation for diagnosis is colonoscopy with biopsy, however, CT colonography can be used if colonoscopy is contraindicated or inappropriate. Once a confirmed diagnosis is made, a staging CT of the chest, abdomen and pelvis is required. Management involves an MDT-based decision, considering factors including TNM staging, the patient’s performance status and patient preference. Localised CRC is usually managed with curative surgical resection and is only avoided if the risks outweigh the benefits. This may be preceded or followed up by radiotherapy and/or chemotherapy. Advanced metastatic or inoperable tumours will be managed with a palliative approach, including palliative surgery, chemotherapy and hormone therapy. In the UK, bowel cancer screening is offered to everyone aged 60 to 74 years old every 2 years in the form of a home Faecal Immunochemical Test (FIT).

Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

HNPCC, aka Lynch syndrome, is an autosomal dominant inherited condition that increases the risk of various malignancies – most commonly CRC(60-80%). It is caused by a defect in a mismatch repair gene, usually MSH2 or MLH1 (90%), causing microsatellite instability. It is the most common hereditary CRC syndrome, responsible for 1-3% of all CRCs. Other malignancies that are commonly associated with HNPCC include endometrial, ovarian, small bowel and liver cancer. The Amsterdam clinical criteria aids diagnosis alongside molecular genetic testing for germline mutations. Patients with HNPCC undergo 2 yearly colonoscopy screening, with the onset of screening determined by the causative gene mutation. All patients should be offered aspirin, which reduces the risk of developing CRC. If a high risk gene mutation is identified, subtotal bowel resection should be considered.

Familial Adenomatous Polyposis (FAP) 

FAP is a rare autosomal dominant condition characterised by the development of hundreds to thousands of colonic polyps by aged 30-40 years. FAP results from a mutation in the APC tumour suppressor gene on chromosome 5. 80% of cases are familial. Without definitive treatment, almost all FAP patients will develop CRC by the age of 40. Those with FAP may be identified through family genetic screening or by presenting with symptoms such as abdominal pain, PR bleeding or symptoms of bowel obstruction. These patients should undergo colonoscopy at the time of diagnosis and then regularly to assess the polyp burden. Patients invariably require total colectomy or proctocolectomy to reduce their CRC risk. Gardner’s syndrome is a variant of FAP where, in addition to colonic polyps, patients are prone to develop extra-intestinal tumours, including desmoid tumours, osteomas, thyroid and skin tumours (lipomas, fibromas and epidermoid cysts).

Diverticular Disease 

Diverticula are small outpouchings of bowel mucosa and submucosa through its outer muscular layer. Risk factors for diverticula formation include increased age, reduced physical activity, raised BMI, low fibre diet and certain medications (NSAIDs and steroids). When symptoms develop that can be attributed to the diverticula, this is termed diverticular disease – this may include intermittent colicky left iliac fossa pain, bloating, constipation and painless fresh red PR bleeding. Acute diverticulitis occurs if the diverticula becomes inflamed – the patient may develop a fever, elevated leu leukocytes and CRP, and tenderness on the PR exam. Diagnosis of acute diverticulitis is made by CT abdomen with contrast. Endoscopy should be avoided during acute inflammation due to the risk of perforation. Diverticula increases the risk of lower GI complications, including abscess or fistula formation, bowel obstruction, GI bleeding, bowel perforation and peritonitis. Disease management depends on the presentation:

Table 2: Management of diverticula-related disease

Angiodysplasia 

Angiodysplasia is the presence of vascular malformations in the GI tract, most commonly the ascending colon and caecum. This results in fragile blood vessels that are prone to leaking, causing GI bleeding. This disease predominantly affects older patients but is also found in those with aortic stenosis, end stage renal failure requiring dialysis, left ventricular assist devices and Von Willebrand disease. Patients may be asymptomatic, or present with GI bleeding and/or symptoms of iron deficiency anaemia. Diagnosis is made during endoscopy (upper GI, colonoscopy and/or capsule endoscopy) or CT angiography if persistent active GI bleeding. Management involves stabilisation with fluid and blood products if bleeding causes haemodynamic instability and, if persistent, uncontrollable bleeding, treatment options include mesenteric angiography and embolisation, colonoscopy with electrocautery, photocoagulation, clipping or epinephrine injections, or surgical bowel resection.

Colitis

Colitis is inflammation of the colon. It occurs secondary to different underlying pathologies:

• Ulcerative colitis/Crohn’s colitis (as part of IBD) – please see “Infection and Inflammation” topic
• Microscopic colitis – please see “Infection and Inflammation” topic
• Infective colitis – please see “Pseudomembranous Colitis” section
• Ischaemic colitis – please see “Ischaemic Bowel Disease” section

Pseudomembranous Colitis

Pseudomembranous colitis is acute inflammation of the colon secondary to infection with Clostridium difficile – a gram positive toxin-producing anaerobic rod. It has a strong association with prolonged use of broad-spectrum antibiotics, which disrupt the normal bowel flora and allow Clostridium difficile to colonise. The most common culprit antibiotics are 3rd/4th generation cephalosporins, ciprofloxacin, clindamycin, carbapenems and broad-spectrum penicillins. Other risk factors include increased age, prolonged hospital stay, PPI use, immunosuppression and previous Clostridium difficile infection. Symptoms include new onset pungent diarrhoea, abdominal pain, fever, nausea and vomiting. The classification of Clostridium difficile infection severity is shown in table 3:

Table 3: Public Health England Classification of Clostridium difficile Infection Severity

Stool samples should be sent for PCR and enzyme immunoassay in all suspected cases of Clostridium difficile. If clinical signs suggest toxic megacolon or bowel perforation, abdominal imaging is necessary. Patients need to be isolated with enhanced PPE for contacts and handwashing with soap and water until 48 hours after diarrhoea has resolved. Care is supportive, with antimicrobial use guided by frequency of reinfection, as shown in tavle 4.

Table 4: Management of Clostridium difficile Infection in Adults

Ischaemic Bowel Disease 

Ischaemic bowel disease is a heterogeneous group of conditions characterised by reduced blood flow to the bowel, resulting in ischaemia which may lead to infarction and necrosis. Ischaemic colitis affects the large bowel, whilst mesenteric ischaemia affects the small bowel.

Ischaemic Colitis

This is the most common type of bowel ischaemia, caused mainly by arterial (but occasionally venous) embolism or thrombus. It usually affects the watershed areas of the large bowel that lack a collateral blood supply – the splenic flexure and rectosigmoid junction. Risk factors include older age, recent cardiac or vascular surgery, irritable bowel syndrome and constipation. It often presents with sudden onset worsening left iliac fossa pain, often with concurrent passage of loose bloody stool. CT abdomen and pelvis with contrast is often the first line investigation, however, findings may not be specific or diagnostic. Colonoscopy may be required to confirm the diagnosis. Most cases resolve spontaneously. If there are persistent symptoms, patients may require hospital admission with a course of antibiotics, low molecular weight heparin, bowel rest and monitoring. Surgical intervention is required for associated complications (peritonitis, massive GI bleeding, fulminant colitis) – usually segmental bowel resection with stoma formation.

Acute Mesenteric Ischaemia (AMI)

AMI is a medical emergency where the small bowel becomes acutely ischaemic from one of the following 4 mechanisms: acute arterial embolism (50%), intestinal hypoperfusion (20-30%), arterial thrombosis (15-25%) or mesenteric venous thrombosis (5%). It typically affects older patients with cardiovascular risk factors, including atrial fibrillation, previous myocardial infarction, atherosclerosis, smoking and congestive heart failure. It presents with sudden onset severe periumbilical pain out of keeping with examination findings. 90% of patients will have leukocytosis. In suspected cases, an urgent contrast CT abdomen and pelvis and CT angiography are required. Once AMI is confirmed, early surgical and intensive care review is needed. Antibiotics should be started as the intestinal mucosal barrier can be damaged by ischaemia causing bacterial translocation. Management options include interventional radiology (IR)-guided endovascular treatment (thrombolysis, transjugular intrahepatic portosystemic shunt and thrombectomy) or urgent laparotomy with bowel resection if there is bowel infarction, perforation or peritonitis.

Chronic Mesenteric Ischaemia (CMI)

CMI is caused by chronic hypoperfusion of the small bowel, usually because of progressive atherosclerosis. It is more common in older female patients with risk factors including atherosclerosis, left ventricular dysfunction, chronic low blood pressure and constipation. It usually presents with recurrent episodes of mild self-limiting generalised abdominal pain, worse after eating, associated with weight loss from food avoidance. Signs include an abdominal bruit and electrolyte and nutrient deficiencies. Diagnosis is confirmed on CT angiography. Asymptomatic patients can be managed with lifestyle interventions, antiplatelet and lipid-lowering therapies. If symptomatic, surgical or IR-guided revascularisation can be performed.