Anatomy and function of the small intestine

The small bowel extends from the pylorus to the ileocaecal valve and ranges in length from 3 to 9 metres. The jejunum, which comprises two-fifths of the small intestine, is of wider calibre than the ileum, and the diameter of the gut lumen narrows progressively from the duodenojejunal flexure to the ileocaecal valve. The small bowel mucosa is supported on a

strong submucosa and comprises a single layer of columnar cells in a villiform structure that dramatically increases the absorptive surface area. Columnar glandular epithelium is interspersed with mucus-secreting cells, Paneth cells and amine precursor uptake and decarboxylation (APUD) cells derived from the neural crest. Between the inner layer of circular muscle and the outer longitudinal layer runs Auerbach’s myenteric plexus, which comprises vagal parasympathetic fibres and sympathetic fibres from the lesser and greater splanchnic nerves. This plexus controls orderly propulsive contractions of the muscular layers of the gut wall. The sympathetic nervous system mediates the sensation of visceral pain, and a submucosal plexus (Meissner’s plexus) of autonomic nerves innervates the glandular cells in the epithelium.

The small intestine is supplied by the superior mesenteric artery, which runs in the root of the small bowel mesentery, supplying the bowel by a series of arterial arcades (Fig. 16.1). These midgut vessels communicate with the coeliac axis through the pancreaticoduodenal arcade. The superior mesenteric supply also communicates with that of the inferior mesenteric artery by contributing to the colonic marginal artery through the left branch of the middle colic artery, which joins to the ascending branch of the left colic artery. Venous blood drains via the superior mesenteric vein to the portal vein. Lymphoid aggregates in the submucosa (Peyer’s patches) are more numerous in the ileum, and lymph drains to regional nodes in the root of the mesentery before passing to the cisterna chyli.

Fig. 16.1 Arterial arcades supplying the small intestine from the superior mesenteric artery.

The principal function of the small bowel is absorption of amino acids, short peptides, sugars and fats, as well as minerals, vitamins and other micronutrients. Its secretory and digestive functions supplement those of the upper gastrointestinal tract. The mucosa is thrown into circular folds (plicae semilunares) and is carpeted by finger-like villi, giving an absorptive area of 200–500 m². Some 5–8 litres of fluid enter the jejunum each day, of which only 1–2 litres normally pass to the colon.

Anatomy and function of the large intestine and appendix

The principle function of the large intestine is water absorption, particularly the proximal colon. The left colon and rectum act as a reservoir until defaecation is appropriate. Mucus is secreted as a lubricant. The large bowel mucosa consists of columnar epithelium interspersed with mucus-secreting goblet cells. The villi are shorter than those of the small intestine, and crypts pass down to the muscularis mucosa, which is supported by a strong submucosa. The large bowel extends from the ileocaecal valve to the upper anal canal (approximately 1.6 metres). The caecum is a blind pouch at the most proximal part of the large bowel. The transverse and sigmoid colon are mobile because they have a mesentery, whereas ascending and descending colon are only partially peritonealized. The true rectum is demarcated by coalescence of the taeniae coli of the sigmoid colon to form a continuous outer muscular tube. The upper third of the rectum has peritoneal cover on its front and sides, the middle third is peritonealized only anteriorly and the lower third is wholly extraperitoneal.

The inferior and superior mesenteric arteries supply the colon and anastomose via a marginal artery (Fig. 16.2) that allows collateral supply in the event of arterial occlusion, but at the splenic flexure this arterial communication may be tenuous. The superior rectal artery is the continuation of the inferior mesenteric artery, supplying the rectum and anastomosing with the middle and inferior rectal arteries (branches of the internal iliac arteries). The inferior mesenteric vein drains into the splenic vein. Lymph channels run along the course of the arterial supply, draining to epicolic and paracolic nodes close to the bowel wall, and to regional nodes at the origin of the superior and inferior mesenteric vessels (Fig. 16.2). Lymph from the rectum drains upwards to superior rectal and inferior mesenteric nodes, whereas anal canal lymph drains to inguinal nodes. Knowledge of the lymphatic drainage has considerable relevance to surgical lymphadenectomy performed as part of radical cancer clearance, as well as to radiotherapy for rectal and anal cancers.

Fig. 16.2 Blood supply of the large intestine from the branches of the superior and inferior mesenteric arteries, with the lymphatic drainage of the colon and rectum.

The appendix is lined by colonic epithelium but has no known function in humans. The submucosa contains prominent lymphoid follicles in childhood that regress in adolescence. In older patients, the lumen may be obliterated by fibrosis. The appendix projects from the medial wall of the caecum some 2 cm below the ileocaecal junction as the taeniae coli converge on the root of the appendix.

History

Painful contraction of the midgut (supplied by the superior mesenteric artery: small bowel, right and part transverse colon) due to obstruction or inflammation results in peri-umbilical colic. Disorders affecting the large bowel, i.e. hindgut (supplied by the inferior mesenteric artery: from distal transverse colon to rectum), are frequently associated with ill-defined lower abdominal colicky pain. Nausea, vomiting and pain are early and predominant features of many small bowel disorders, particularly obstruction. In contrast, large bowel conditions may present with poorly defined features including abdominal distension and altered bowel habit; vomiting is a late feature. Normal bowel frequency ranges from one motion in 3 days, up to 3 motions/day. The passage of blood or mucus per rectum is a common feature of large bowel disease. It is important to differentiate ‘outlet-type’ bleeding from sinister blood loss, when the blood is mixed with the stool and there may be associated altered bowel habit or tenesmus. Outlet bleeding is typically bright red and may be present only on toilet paper or spattered in the pan, separate from the stool. There may be associated perianal pain, due to fissure or prolapsed piles. Blood originating from the distal bowel is usually bright red, whereas blood coming from the upper gastrointestinal tract is usually altered by gut bacteria and becomes black (melaena). Weight loss, malaise and anaemia are common non-specific features of intestinal disease.

Examination

The oral mucous membrane, hands, fingernails, eyes and conjunctiva should be inspected. Examination of the abdomen may reveal distension, a mass or visible peristalsis. In thin subjects, the caecum is often palpable, and the descending and sigmoid colon may be palpable when loaded with faeces. Hepatomegaly due to metastatic disease should be excluded. Abdominal auscultation determines the presence and pitch of bowel sounds and occasionally reveals an arterial bruit. Digital rectal examination is essential to detect a tumour and may also reveal blood or mucus. In patients with lower gastrointestinal symptoms, there is no rationale for checking the faeces for occult blood, as the sensitivity of the guaiac faecal occult blood (FOB) test is low. Investigation should not be influenced by FOB testing in the assessment of symptomatic patients.

Investigation of the luminal gastrointestinal tract

Investigation of diarrhoeal illnesses should include stool culture with sensitivities, tests for Clostridium difficile toxin as well as cysts, ova and parasites. Imaging modalities for small bowel investigation comprise plain radiography, magnetic resonance imaging (MRI) enteroclysis, barium follow-through, small bowel enema, computed tomography (CT), fibreoptic enteroscopy, capsule video-endoscopy, labelled white cell radionuclide scanning and labelled red cell radionuclide scanning. The terminal ileum can be inspected at colonoscopy, double-contrast barium enema frequently allows visualization of the terminal ileum, and a pneumocolon technique can also be used with barium follow-through to obtain double-contrast views of the terminal ileum. Duodenal biopsy undertaken at upper gastrointestinal video-endoscopy to identify the characteristic subtotal villous atrophy is the gold standard investigation of suspected coeliac disease. However, coeliac disease is frequently diagnosed by serum ELISA assays for auto-antibodies, including anti-endomysial, IgA anti-gliadin or tissue transglutaminase (tTG) antibodies. Tests of absorptive capacity are now rarely used. Bacterial overgrowth can be assessed using the glucose breath test, ¹⁴C-xylose and ¹⁴C-glycocholate breath tests. Small bowel aspiration can be carried out by nasojejunal tube or at enteroscopy for bacterial culture. Faecal calprotectin is a non-specific test of intestinal inflammation that can be used to monitor inflammatory bowel disease activity.

Direct inspection of the large bowel includes proctoscopy, rigid sigmoidoscopy, flexible sigmoidoscopy and colonoscopy. These techniques allow biopsy and snare removal of colorectal polyps using cauterizing diathermy. Plain radiography is used extensively in the emergency situation but is seldom of value in elective investigation. CT double contrast radiography of the large bowel has largely superseded double contrast barium enema to allow inspection of the mucosa. CT also has considerable utility in the assessment of the acute abdomen. CT of chest, abdomen and pelvis is routinely used in staging of colon and rectal cancer, along with MRI for rectal cancer. Positron emission tomography (PET) after administering a fluoride¹⁸ labelled tracer (fluorodeoxyglucose) that is metabolized by tumours (FDG-PET CT) has recently been introduced, although it is generally reserved for staging of complex colorectal cancer cases being considered for more major multiorgan resections. Colonic transit can be assessed in cases of suspected megacolon or slow-transit constipation by administering radio-opaque markers to estimate large bowel transit.

Appendicitis

Acute appendicitis remains the most common acute abdominal emergency in childhood, adolescence and early adult life and is discussed in Chapter 12.

Appendiceal tumours

Crohn’s disease

Although originally described as a disease affecting the terminal ileum, any part of the gastrointestinal tract can be involved, from mouth to anus. In 50% of cases both small and large bowel are involved, whereas in 25% of cases large bowel alone is affected. The incidence is increasing in developed countries and the annual incidence rate is currently 5–7 cases per 100 000 in the UK population. At the time of initial clinical presentation, the features of Crohn’s disease may be indistinguishable from those of ulcerative colitis. Indeed, in cases of colonic Crohn’s disease, it may be difficult to differentiate the two conditions, even after resection and histological assessment.

Cigarette smoking is the single most important risk factor for developing the disease, and is associated with increased disease severity and frequency of relapse, as well as the need for surgical intervention. However there is a substantial heritable component to the disease. There is also evidence for the involvement of immunological factors and the gut bacterial flora in the pathogenesis of Crohn’s disease. Recently, over 30 genetic loci have been identified that each contribute a small effect in host–bacteria interaction. These include CARD15 (NOD2), dysregulation of adaptive immunity (IL23R), and deficient autophagy (ATG16L1, IRGM).

Pathology

Macroscopically, Crohn’s disease produces a cobblestone appearance, in which oedematous islands of mucosa are separated by crevices or fissures; these can extend through all coats of the bowel wall. Serpiginous ulceration is common so that fibrosis may result in multiple strictures of varying length. Multiple areas of inflammation are common with intervening normal bowel (skip lesions, Fig. 16.3). Full-thickness involvement of the bowel wall leads to serosal inflammation, adhesion to neighbouring structures, and sinus or fistula formation. Microscopically, there are deep fissuring ulcers, oedema and inflammatory cell infiltrates with foci of lymphocytes and non-caseating granulomas in 50% of cases.

Fig. 16.3 Small bowel follow-through showing Crohn’s disease strictures (arrow indicates long stricture).

Clinical features

Crohn’s disease is a chronic disorder with exacerbations, remissions and a varied clinical presentation. Continuous or episodic diarrhoea is associated with recurring abdominal pain and tenderness, lassitude and fever. Declining general health, malabsorption and weight loss, with failure to thrive and to reach developmental milestones, are common in affected children.

Examination may reveal malnutrition and there may be a palpable abdominal mass. There may be features of subacute intestinal obstruction, and this may be due to active disease, stricturing of ‘burnt-out’ disease, or adhesions from previous surgical intervention. Fistula formation occurs in 20% of patients with small and large bowel disease, but less in those with disease restricted to the large bowel. Fistulae may communicate with adjacent loops of bowel, other viscera (e.g. bladder, vagina) or the skin. External fistulae may result from surgical intervention and commonly involve the anterior abdominal wall or perineum (Fig. 16.4). Abscesses can result from chronic bowel perforation, but free perforation is relatively uncommon because the inflamed segment usually adheres to surrounding structures. Although less common than in ulcerative colitis, toxic dilatation can complicate colonic disease. Fulminant Crohn’s colitis is shown in Figure 16.5; deep ulcers and fibrosis with mucosal oedema and inflammation can be seen.

Fig. 16.4 Severe perianal Crohn’s disease with fistulation.

Fig. 16.5 Fulminant Crohn’s colitis.

It is essential to consider malignancy in patients with long-standing Crohn’s disease, with or without symptoms. There is an elevated risk of colorectal adenocarcinoma: 2.5-fold overall and 4.5-fold for colonic disease, with a 10-year cumulative risk following diagnosis of 2.9%. Evidence is limited that surveillance provides protection and many patients with longstanding colonic Crohn’s eventually come to colectomy. Crohn’s disease is also associated with ∼︀30-fold excess risk of small bowel adenocarcinoma, but because that cancer is rare, the absolute risk only amounts to 0.2% at 10 years and 2.2% at 25 years after diagnosis.

25% of patients with small bowel Crohn’s disease and 75% with large bowel disease have troublesome anal lesions, including abscess, fistula, fissures, ulceration, oedematous skin tags, anorectal stricturing. Anal fissures are often multiple and indolent, and extend to involve any part of the perineum, including the vagina or scrotum. Systemic manifestations of Crohn’s disease include anterior uveitis, iritis, polyarthropathy, ankylosing spondylitis, liver disease (e.g. sclerosing cholangitis) and erythema nodosum. Terminal ileal involvement may result in gallstones, with increased incidence following ileocaecal resection.

Investigations

Assessment of nutritional status, including serial weight measurement, is essential. Anaemia may be due to: iron deficiency from chronic blood loss and rarely due to malabsorption; a normocytic anaemia of chronic disease; macrocytic anaemia from vitamin B₁₂ or folate malabsorption. Elevated acute-phase proteins such as C-reactive protein are useful in monitoring disease, though not specific for diagnostic purposes. Until recently, the diagnosis was most frequently made on barium follow-through: typical features are shown in Figure 16.6 – rose-thorn ulcers, long irregular terminal ileal stricture at the site of previous ileocaecal resection. Active disease produces radiological evidence of thickening, luminal narrowing and separation of loops, and is often associated with mucosal ulceration, deep fissuring ulcers and cobblestone appearance. Skip lesions and fistula formation may be apparent. However, MRI enteroclysis (image enhanced by administering oral osmotically active agent – e.g. PEG) has progressively become the investigation of choice (Fig. 16.7), which also has the advantage of limiting radiation exposure. Rectal examination, proctoscopy, sigmoidoscopy and colonoscopy determine disease extent and biopsy of inflamed bowel is mandatory. Newer investigative techniques include video-capsule endoscopy (Fig. 16.8), enteroscopy, and CT colonography. Double-contrast barium enema still has a place for assessing disease extent and delineation of fistulae.

Fig. 16.6 Small bowel contrast enema in Crohn’s disease, showing a long irregular stricture and typical rose-thorn ulceration.

Fig. 16.7 Small bowel MRI showing thickened strictured small bowel in Crohn’s disease.

Fig. 16.8 Video-capsule enteroscopy of Crohn’s disease.

A Extensive ulceration and structuring. B A single deep ulcer.

Ulcerative colitis

The annual incidence of ulcerative colitis is ∼︀10/100 000 population in Westernized countries but rare in developing countries. The aetiology is incompletely understood, but genetic, immunological and dietary factors all play a part. The disorder may affect any age group but peak incidence is in early adulthood. In the majority of cases, the disease is contiguous, affecting the rectum and extending proximally (see Table 16.1). In 5% of cases, it is segmental and the rectum is occasionally spared. There is substantial risk of colorectal adenocarcinoma in cases with pancolitis. Although ulcerative colitis is primarily a disease of the large bowel, systemic manifestations (iritis, polyarthritis, sacroiliitis, hepatitis, erythema nodosum, pyoderma gangrenosum) can occur. Primary sclerosing cholangitis (PSC) affects 2–5% of cases of ulcerative colitis; it tends to indicate severe disease and predicts complications. Patients with PSC may develop liver failure and require liver transplantation.

Pathology

The characteristic feature of ulcerative colitis is inflammation restricted to the mucosa and submucosa of the large bowel. In severe episodes, there may be full-thickness involvement with inflammatory infiltrate. Abscesses develop at the base of the colonic crypts, which burst and coalesce to form crypt abscesses. These undermine the mucosa, resulting in ulceration (Fig. 16.9) and oedema of the intervening mucosa, which may form inflammatory pseudopolyps. Histologically, as well as ulceration and crypt abscesses, there is chronic inflammatory cell infiltrate, crypt architectural distortion and goblet cell depletion, but granulomas are absent. The colon loses its haustrations and becomes thick and rigid. Stricturing is uncommon and its presence should raise the possibility of Crohn’s disease. There can be difficulty in distinguishing ulcerative colitis from Crohn’s colitis both pathologically and clinically, when the term ‘indeterminate colitis’ is used to denote uncertainty. There may even be migration from one disease entity to the other. There are important implications for surgical treatment, since ileo-anal pouch should be avoided in cases of Crohn’s colitis.

Fig. 16.9 Resected colonic specimen of fulminant ulcerative colitis showing denuded colonic epithelium.

Investigations

Expert colonoscopy is the mainstay of diagnosis and assessment of disease extent/severity. Endoscopic features of severe acute colitis are shown in Figure 16.10. Barium enema is infrequently used in modern inflammatory bowel disease practice and may risk perforation. Typical changes include loss of haustrations, fluffy granularity of the mucosa, and pseudopolyps. Undermining ulcers may create a double contour to the edge of the colon. Widening of the retrorectal space, due to perirectal inflammation and reduced distensibility of the rectum, is common. In longstanding colitis, the bowel may become short and featureless, resembling a smooth tube (lead-pipe colon). In an acute attack, plain films of the abdomen may reveal a dilated gas-filled colon in which pseudopolyps are evident. When toxic dilatation is suspected, daily plain X-rays are essential to monitor progress (Fig. 16.11). ‘Backwash ileitis’ may produce a dilated and featureless terminal ileum in which the mucosa appears granular. In the acute phase, it is essential to collect stool cultures to exclude supervening bacterial infection and especially C. difficile.

Fig. 16.10 Colonoscopic appearance of severe acute colitis.

Fig. 16.11 Plain abdominal radiograph of fulminant colitis showing distension and mucosal oedema and thumbprinting.

Surveillance colonoscopy has an important place in the management of long-standing colitis to detect dysplasia or supervening cancer.

Small bowel neoplasms

Small bowel tumours account for less than 5% of all gastrointestinal neoplasms.

Malignant tumours

Malignant small intestinal tumours are rare and frequently diagnosed late because symptoms are non-specific and so initial presentation may be at laparotomy for small bowel obstruction. In symptomatic cases, imaging modalities include MRI enteroclysis, barium follow-through, CT scan, flexible enteroscopy and video-capsule endoscopy.

Gastrointestinal stromal tumours (GIST)

GISTs are the most common form of mesenchymal tumour of the intestinal tract. The lesions are derived from smooth muscle of the gut tube; 50–60% arise in stomach, 20–30% in small bowel, 10% in rectum and 5% in oesophagus. There is a spectrum from benign to malignant. Malignant lesions have a poor prognosis, tending to recur locally and to metastasize. Expression of the oncogene c-Kit differentiates malignant from benign characteristics. The Kit protein is a transmembrane tyrosine kinase receptor and malignant GISTs have a mutation in the c-Kit gene or the platelet-derived growth factor receptor alpha gene (PDGFRA) which causes up-regulation of tyrosine kinase activity and promotes tumour cell growth. Understanding the involvement of c-Kit in GIST development and progression has allowed the development of new effective tyrosine kinase inhibitor anticancer agents specifically designed to inhibit Kit or PDGFRA, such as imatinib mesylate.

Small bowel adenocarcinoma

The duodenum and upper jejunum are the most common sites of this rare tumour. Adenocarcinomas, which are usually poorly differentiated and are mucin-secreting, may be associated with FAP (familial adenomatous polyposis) or HNPCC (Lynch syndrome). Resection of the affected segment is carried out, but palliative bypass may be all that is possible, as the disease often presents late.

Lymphoma

Small bowel is the most common site for lymphoma to arise in the intestine and may present as intermittent obstruction, bleeding or perforation. Coeliac disease is associated with an increased risk of various types of non-Hodgkin’s lymphomas but particularly enteropathy-type T-cell lymphoma (ETTL). Antigliadin, anti-TTG and anti-endomysial antibodies should be determined and a biopsy of adjacent normal small intestine or duodenum should always be assessed for villous atrophy in cases of lymphoma. Treatment is frequently surgical in the first instance because the diagnosis is made histologically after small bowel resection, but chemotherapy is required in most cases.

Carcinoid tumour

The small bowel is the second most common site for carcinoid tumour (after appendix). Metastasis to lymph nodes is common at presentation, and obstruction and bleeding are the usual modes of presentation. Abdominal CT typically reveals a small bowel mass lesion with prominent calcification (Fig. 16.12). There may be features of the carcinoid syndrome in the presence of liver metastasis. Tests for urinary 5-HIAA (hydroxy-indole-acetic acid) and blood levels of chromogranin A should be undertaken. The primary tumour should be resected where possible. Lesions are frequently multifocal and may require multiple resections.

Fig. 16.12 CT showing small bowel carcinoid tumour with characteristic calcification and desmoplastic reaction. There is small bowel obstruction proximal to the lesion.

Peutz–Jeghers syndrome

Peutz–Jeghers syndrome is an autosomal dominant inherited disorder with high penetrance. The disease is caused by mutations in the LKB1 gene, located on the short arm of chromosome 19. Some cases are due to as yet unmapped genes. The clinical manifestations include gastrointestinal polyps and melanin pigmentation at mucocutaneous junctions, characteristically around the mouth and eyes. Occasionally there is pigmentation on the dorsum of the hands and feet. Affected individuals are at risk of colorectal, gastric, pancreatic, breast, and ovarian cancers. Small intestinal and gastric cancers occur in around 7% of patients and colorectal cancer in 10–20%.

Clinical features

Most cases present in childhood or adolescence. There are usually dark brown or bluish spots on the lips and inside the mouth. The face, palms, soles, arms and perianal region can also be affected, but patients without pigmentation have been described. The usual presentation is with abdominal pain or obstruction due to intussusception of a polyp, but rectal bleeding and iron deficiency anaemia are also common. The diagnosis may be made in childhood or early adulthood on clinical grounds due to the association of abdominal colic and typical pigmentation. The small bowel investigation of choice in suspected Peutz–Jeghers Syndrome is MRI enteroclysis (Fig. 16.13). This avoids the radiation dose associated with repeated barium small bowel follow-through or CT examinations.

Fig. 16.13 Peutz–Jeghers syndrome.

A Abdominal MRI (coronal view) showing multiple polypoid filling defects due to hamartomatous polyps. B Cross-sectional MRI of a large jejunal polyp.

Jejunal diverticulosis

Jejunal diverticulae are acquired during adult life. Occasionally, only one or two diverticula are present but often diverticulosis is very extensive, with multiple wide-mouthed sacs caused by herniation of mucosa into the mesentery at the site of vessel penetration of the gut wall. Jejunal diverticulosis may be first diagnosed at laparotomy for complicated disease, or incidentally on imaging studies (Fig. 16.14). Diverticulae may cause bleeding, inflammation, malabsorption (due to bacterial over-colonization) and perforation. Occasionally, fish bones or NSAID tablets can become trapped in a diverticulum and cause local perforation. In symptomatic disease the extensive nature of the disorder often necessitates a conservative approach with antibiotics and intravenous fluids. However, a bowel segment with complicated diverticulosis may require limited resection, leaving other affected areas in situ.

Fig. 16.14 Jejunal diverticulosis.

Radiation enteritis

External beam irradiation or radioactive implants can cause enteritis. The terminal ileum is the most commonly affected site within the small bowel. In the acute phase, oedema, inflammation and ulceration may produce watery diarrhoea, lower abdominal pain, tenesmus, mucous discharge and rectal bleeding. Subsequently, the bowel may thicken, with fibrosis and stricture which may require resection. The small bowel may fistulate to other loops, to large bowel or to the vagina. The involved segments require resection but anastomotic healing is frequently compromised because of the radiation damage.

Small bowel ischaemia

Small intestinal ischaemia is usually due to atheromatous occlusion with superadded thrombosis of the superior mesenteric artery. Factors predisposing to mesenteric thrombosis include thrombophilia, hyperviscosity syndromes, dehydration, hypovolaemia or hypoperfusion of the gut resulting from trauma, cardiogenic shock, cardiac arrhythmia and septic shock. Arterial embolism can result from atrial fibrillation or recent myocardial infarction. In a third of patients dying from acute ischaemic necrosis of the midgut, there is no demonstrable occlusion of a major vessel, and in these cases low perfusion is responsible. Other causes include polycythaemia, sickle cell disease and disseminated intravascular coagulation. Arteritis should be suspected where there are other stigmata or a history of disseminated arteritis, such as pre-existing renal failure. Impaired venous return from the gut can be due to hyperviscosity syndromes and prothrombotic tendency, but are also seen in the presence of malignancy and portal hypertension.

Ischaemic necrosis may progress to necrosis of all bowel layers with gangrene and perforation. Acute occlusion of the superior mesenteric artery (SMA) is predominantly a disease of the elderly and leads to complete midgut necrosis.

Chronic mesenteric ischaemia

Chronic mesenteric ischaemia results in repeated bouts of ill-defined colicky central abdominal pain, typically commencing 20–30 minutes after eating, leading to ‘fear of food’ and almost universally resulting in weight loss. Diagnosis is often elusive and is usually preceded by extensive investigation to exclude other conditions of the small or large bowel, such as Crohn’s disease and malignancy. Mesenteric arteriography may be diagnostic but must be taken in the context of symptoms because atheromatous change in mesenteric vessels is common. Mesenteric revascularization may be feasible in a minority of cases.

Pseudo-obstruction and nonmechanical gut functional disorder

Colonic diverticular disease

Colonic diverticulosis is extremely common in developed countries, being apparent to some extent in more than 60% of people over the age of 70 years. The true population prevalence is unknown because estimates are based on indirect information from people who have undergone GI investigation for some reason. In most cases it is asymptomatic, often being noted incidentally on investigation for symptoms that are not due to the disease itself. Diverticulosis is the preferred term for such cases. Symptomatic diverticular disease can be classified as uncomplicated or complicated as discussed below. Diverticulosis is an acquired condition linked with a low-fibre diet, being rare in populations whose staple diet is high in fibre.

Although the whole colon can be affected, the sigmoid colon is most commonly involved, related to the high intraluminal pressure at this site caused by a low-residue diet. Muscular hypertrophy can be detected radiologically before diverticulae develop. Pulsion diverticulae emerge between the mesenteric and antimesenteric taeniae and result from herniation of mucosa through the circular muscle at the sites of penetration of feeding arteries. The true rectum is not affected because of differences in the arrangement of the blood supply and also because the outer longitudinal smooth muscle tube encompasses the full circumference of the rectum, contrasting with the colonic taeniae.

In addition to the common acquired diverticular change that may affect the caecum, there is a rare congenital solitary diverticulum of the caecum that can arise from the medial wall close to the ileocaecal valve and can extend upwards retroperitoneally. This may become obstructed by a faecolith and inflamed, producing a clinical picture indistinguishable from appendicitis.

Colonic diverticulae may give rise to intermittent lower abdominal/left iliac fossa pain, altered bowel habit, urgency of defaecation and episodic rectal bleeding. The sigmoid colon may be tender on examination. Barium enema reveals muscle thickening and multiple diverticula (Fig. 16.17). Abdominal CT, either as CT colonography or plain abdominal CT, is used increasingly and provides an assessment of the degree of surrounding inflammation and/or abscess formation, in addition to extent of the diverticular changes (Fig. 16.18). Colonoscopy reveals the ostia of diverticulae and may show surrounding inflammation.

Fig. 16.17 Diverticular disease, barium contrast radiography.

Fig. 16.18 Diverticular disease, CT showing local perforation and collection (arrowed).

In the management of uncomplicated diverticular change, patients should be advised to take a high-fibre diet, supplemented by bran or a bulk laxative such as methylcellulose. Stimulant laxatives and purgatives are to be avoided. Antispasmodics, such as propantheline or mebeverine, may be useful if there is smooth muscle spasm and colicky pain. There is evidence that NSAIDs increase the risk of complications and advice should be given to avoid these agents wherever possible. Surgical resection of the affected segment may be indicated if there are persistent symptoms, or when carcinoma cannot be excluded by radiology or colonoscopy (EBM 16.2).

Ischaemic colitis

In almost 50% of cases, ischaemia of the large intestine is transient and necrosis is confined to the mucosa and submucosa. The patient presents with lower abdominal pain, nausea, vomiting and bloody diarrhoea. Cardiovascular comorbidity should raise suspicion of the diagnosis. Examination reveals tenderness and guarding, often maximal in the lower left abdomen. There is usually a leucocytosis and pyrexia. Plain abdominal radiography may reveal a thickened segment of colon and thumb printing due to submucosal oedema, which may be evident on barium enema or CT (Fig. 16.19). Contrast studies should be carried out with water-soluble contrast such as gastrografin, because of the risk of perforation. The splenic flexure and sigmoid colon are most often affected (Fig. 16.20). Ischaemic colitis is treated conservatively in the first instance unless abdominal signs reveal peritonitis, but symptoms should resolve after a few days of supportive therapy. Further assessment by colonoscopy is indicated once the acute episode has settled, to exclude diverticular disease and colorectal cancer.

Fig. 16.19 Typical features of ischaemic colitis.

Barium enema showing mucosal oedema and ‘thumb printing’.

Fig. 16.20 CT scan showing gross mucosal thickening typically affecting the left side of the colon and sigmoid colon (arrowed).

Gangrenous ischaemic colitis

The clinical presentation is localized or generalized peritonitis. Surgery is required for patients deemed sufficiently fit following consultation with the patient wherever possible, or with the family. Without surgery, death is virtually certain. However, surgical mortality is around 50%. Resection of the infarcted segment with colostomy formation is the rule, as poor blood supply usually militates against a primary anastomosis.

Ischaemic stricture of the colon

Colicky abdominal pain, constipation and abdominal distension, following a history of an attack of bloody diarrhoea or a documented episode of ischaemic colitis, may suggest the diagnosis of ischaemic stricture. The patient may present with frank large bowel obstruction. Contrast CT or enema reveals a smooth narrowing of a segment of bowel, with a funnelled appearance at either end but lacking the shouldered appearance of a malignant stricture (Fig. 16.21). Colonoscopy reveals a smooth, narrowed stricture with unremarkable biopsies, or occasionally histology may reveal evidence of chronic fibrosis. Resection is usually required, but some cases never come to medical attention.

Fig. 16.21 Barium enema showing the smooth tapered appearance of a chronic benign stricture.

Irritable bowel syndrome

Although not discussed here, irritable bowel syndrome is a common functional bowel disease that is highly relevant to surgical practice because it presents with symptoms that are indistinguishable from structural bowel disease, such as inflammatory bowel disease and cancer. Because of the lack of discriminatory clinical features, the diagnosis is largely one of exclusion, once appropriate investigation has ruled out other disorders.

Volvulus

Volvulus of the colon most commonly affects the sigmoid colon, and rarely the caecum, and is an important differential diagnosis of any cause of large bowel obstruction, such as cancer and diverticular disease. Sigmoid volvulus is due to a twist around a narrow origin in the sigmoid mesentery. It is an acquired condition and is the most common cause of large bowel obstruction in countries with a high level of dietary fibre and those affected are frequently young adults. By contrast in the UK, patients are usually elderly and chronic constipation is associated. The clinical presentation is of a bowel obstruction with lower abdominal pain, abdominal distension, nausea, vomiting and absolute constipation. Occasionally, the patient may present with sepsis owing to an established visceral perforation. Plain radiography reveals a characteristic Y-shaped shadow surrounded by a grossly distended colon arising out of the pelvis on a plain radiograph (‘coffee bean’ sign) (Fig. 16.22). Water-soluble contrast radiography or CT may show the characteristic ‘beaking’ at the site of the twist.

Fig. 16.22 Sigmoid volvulus.

Plain abdominal radiograph showing characteristic ‘coffee bean’ sign.

Sigmoid volvulus can be treated conservatively in the emergency situation by reduction and deflation, using rigid or flexible sigmoidoscopy and the placement of a large-bore tube into the sigmoid. Elective sigmoid colectomy following full bowel preparation is curative in the fit patient. In frail and demented patients or those with significant cardiac or other comorbidity, a conservative approach may be taken, but a relapse of the twist is very likely and frequent readmission is the rule. Hence, surgery is the preferred option wherever possible (Fig. 16.23).

Fig. 16.23 Operative view of gross distension in sigmoid volvulus.

Caecal volvulus is a misnomer because it involves both the caecum and the small intestine, with the twist occurring around the superior mesenteric artery. The presence of a congenital intraperitoneal caecum predisposes to volvulus. It is usually suggested by plain radiography showing anticlockwise rotation of dilated small bowel loops around a grossly distended caecum. Caecal volvulus usually requires emergency laparotomy because of the danger of compromise to the arterial supply of substantial lengths of the small bowel.

Angiodysplasia

Angiodysplasia is an important cause of massive lower gastrointestinal haemorrhage, and may co-exist with diverticular disease. The acquired submucosal arteriovenous malformations commonly affect the caecum and sigmoid colon, but any part of the large bowel can be involved. The diagnosis may be secured by visualization of a bleeding point at colonoscopy. Bleeding angiodysplastic lesions can be treated by angiographic embolization, by laser treatment or injection sclerotherapy at colonoscopy, or by resection at emergency laparotomy.

Pseudomembranous colitis

Pseudomembranous colitis is almost always a healthcare associated infection (HAI) associated with the use of oral broad-spectrum antibiotics. C. difficile is the organism responsible in the vast majority of cases, and can be diagnosed by stool culture or by assays for the presence of C. difficile toxin in stool or blood. Necrosis of the colorectal mucosa causes watery diarrhoea, toxaemia, shock and collapse. The stools are watery, green, foul-smelling and blood-stained, and often contain fragments of mucosal slough. A typical pseudomembrane may be visible on sigmoidoscopy but is not a prerequisite. Biopsy confirms the diagnosis. The patient may be profoundly unwell, with dehydration and sepsis, and may require intensive resuscitation with intravenous fluid replacement. Treatment consists of oral metronidazole or vancomycin for 10 days. Severe cases may develop a toxic megacolon indistinguishable from that associated with inflammatory bowel disease. This surgical emergency requires colectomy and ileostomy. An ileorectal anastomosis can be performed at a later date when the patient is fully recovered.

Microscopic colitis

Other rare subtypes of colitis are collagenous and lymphocytic colitis (collectively known as microscopic colitis), characterized by chronic diarrhoea, normal endoscopic and radiological findings, and typical findings on histological examination of colonic tissue. Microscopic colitis occurs more commonly in females; it can affect people of all ages but mean age is in the seventh decade. Collagenous colitis is characterized by macroscopically normal colonic mucosa overlying a typically thickened subepithelial collagen band on histological examination. Lymphocytic colitis is characterized by an increased number of lymphocytes in the submucosa but lacks the features of either ulcerative or Crohn’s colitis. It can have a segmental distribution and so differentiation from Crohn’s colitis is important. There is a loose association with coeliac disease and measures should be taken to exclude this condition. There may be an association with a coexistent autoimmune disorder or the use of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs). Treatment comprises avoidance of caffeine and other aggravating factors known to the patient. 5-ASA agents may have a place in those not responding. Anti-diarrhoeal agents may be helpful. The disorder tends to resolve with such measures, but some resistant cases may benefit from topical steroid.

Hirschsprung’s disease

Hirschsprung’s disease affects 1 in 5000 live births and is due to the absence of ganglion cells in Auerbach’s and Meissner’s plexuses. It is an inherited disorder showing incomplete penetrance and variable expressivity. In some cases, there is a strong familial component, and mutations of the RET oncogene on chromosome 10 are responsible for most of these. RET gene mutations are also associated with multiple endocrine neoplasia (MEN) type II. In most cases, 5–20 cm of the distal large bowel is affected. The disease usually presents in childhood, but late presentation in adult life is not unknown. Loss of peristalsis in the affected segment leads to large bowel obstruction with gross distension of the colon proximal to the aganglionic segment. The differential diagnosis in the neonate includes imperforate anus and meconium ileus, and in older children, megacolon acquired as a result of chronic constipation. Ischaemic colitis and, in children, necrotizing enterocolitis have been reported due to superinfection with Staphylococcus aureus.

MRI is replacing barium enema, but either will reveal dilated bowel above the narrowed aganglionic segment. Lack of ganglia is confirmed by full-thickness biopsy of the abnormal area. In neonates, treatment consists of irrigation of the bowel with saline, followed by operation at about 6 weeks to bring ganglionated bowel down to the anal verge. In older children, a preliminary colostomy may be needed to allow bowel decompression. In the rare instance where the disease is not diagnosed until adulthood, the proximal colon is usually dysfunctional due to chronic megacolon and proctocolectomy, and ileo-anal pouch reconstruction may be preferable to anterior resection.

Acquired megacolon and idiopathic slow-transit constipation

In some children, chronic constipation may result in megacolon and is associated with behavioural problems and difficulty with toilet training. The initial complaint is often faecal soiling, but a vicious cycle of constipation and anal fissure may ensue. In adults, defaecatory problems ranging from idiopathic slow-transit constipation to adult megacolon and megarectum may arise. Electrophysiological studies have shown changes reminiscent of Hirschsprung’s disease affecting the whole of the large bowel, and there may be associated gastric motility dysfunction. Examination reveals gross faecal loading of the colon and rectum. Barium studies reveal a capacious and poorly contracting bowel with huge redundant loops. Transit studies with radio-opaque markers or a radiolabelled enema typically show delayed transit.

Initial conservative management with aperients, bulk laxatives and regular enemas is successful in many cases, but faecal disimpaction under general anaesthesia may be required. Colectomy may be indicated in resistant cases but specialist advice should be sought, as severe cases are often due to neuropathy of the whole gut and surgery may not be curative.

Stoma

Intestinal stomas have an important place in the management of small and large intestinal disease. An ileostomy is formed by bringing out the ileum through the abdominal wall, usually through the rectus muscle in the right iliac fossa. Ileal bowel content is irritant to skin and a spout is fashioned to allow appliances to be fitted and so prevent skin contact with bowel content (Fig. 16.24). Ileostomy comprises either an ‘end’ stoma, or a ‘loop’ or ‘defunctioning’ stoma. It may be employed as an adjunct to resectional surgery when the disease process prevents re-anastomosis, or as a temporary stoma to allow a distal anastomosis to heal, such as for a low colorectal or ileoanal anastomosis. End-ileostomy is used when the colon has been removed, and occasionally when small intestine distal to the stoma has been removed, as in extensive Crohn’s disease.

Fig. 16.24 Ileostomy sited in the right iliac fossa and demonstrating a spout.

The colon can be brought out as an end or a loop colostomy, usually through the rectus muscle in the left iliac fossa. Transverse colostomy is seldom used in modern surgical practice but is brought out onto the right upper quadrant. A colostomy does not require a spout, as faeces are not usually irritant to the skin. End-colostomy is used as part of a Hartmann’s procedure and is an integral part of an abdominoperineal resection for rectal cancer (see below). A loop colostomy of the sigmoid colon is used to divert faeces from a diseased anorectum, such as during the management of complex perianal fistula or faecal incontinence surgery. It may also be used as palliation for pelvic cancer or during radical radiotherapy for rectal cancer.

Intestinal fistula

A fistula is an abnormal communication between two epithelialized surfaces, and can manifest as a communication between intestine and other parts of the gastrointestinal tract, skin, urinary tract or vagina. Intestinal fistulae may arise as part of a disease process (Crohn’s, complicated diverticular disease or radiation enteritis) or as an iatrogenic complication, such as leak from a surgical anastomosis. Anastomotic leak may result in a cutaneous fistula, with bowel content appearing through the wound several days after intestinal surgery. The overall leak rate from colorectal surgery is around 5%, but around 10% for colorectal anastomoses. Anastomotic leak may present as a rectovaginal fistula, when defunctioning stoma with conservative management may be the best option but laparotomy and drainage of pus combined with taking down of the anastomosis with the formation of a stoma may be required. Radiation fistula typically presents several months or years after the primary treatment, owing to the late development of endarteritis obliterans and chronic microvascular ischaemia. Malignant tumours of the upper and lower intestine can result in any combination of fistulation. Actinomycosis and tuberculosis are rare causes of cutaneous fistula. Treatment of disease-related fistula usually requires management of the primary problem.

Colorectal adenoma

Neoplastic epithelial polyps are classified as tubular, tubulovillous or villous adenomas, depending on their histological architecture, and such classification has clinical relevance with respect to cancer risk. Adenomas affect 40% of people over 50 years of age and 70% of those aged 65–69 years. Tubular adenomas account for 75% of all adenomas and are frequently pedunculated but may be sessile. Villous adenomas account for 10% and tubulovillous types for 15% of all adenomas. However, villous adenomas account for 60% of lesions larger than 2 cm. Villous tumours are most commonly located in the rectum and may be very large, carpeting the rectum. Around 50% of such tumours have a focus of carcinoma at presentation. Villous adenomas greater than 1 cm in diameter have an approximately 30% chance of malignancy, whereas the risk in a similar-sized tubular adenoma is around 10%. Multiple adenomas are common, with 24% of patients having at least two tumours.

Clinical features

The vast majority of polyps are asymptomatic, but symptoms include rectal bleeding or large bowel colic (especially when a large polyp intussuscepts). Occasionally, a rectal polyp may prolapse through the anus. Patients with giant villous adenoma of the rectum may present with severe watery diarrhea due to excessive mucus loss. This may result in dehydration and electrolyte depletion (profound hyokalaemia is typical). Rectal adenomas may be palpable, but villous tumors are soft and may be missed by the inexperienced finger. Distal polyps are detected readily by sigmoidoscopy, but there is a need for full colonoscopy in view of the risk of synchronous lesions (Fig. 16.25).

Fig. 16.25 Endoscopic appearance of a rectal adenomatous polyp.

Management

Colonoscopic polypectomy using an electrocautery snare prevents future risk of malignant conversion as well as enabling histological assessment. Small adenomas can be biopsied and a current applied to destroy the entire polyp (‘hot’ biopsy). In many cases, polypectomy is the only treatment required, even when there is a malignant focus, so long as there are none of the following features: poor differentiation, stalk invasion at the resection margin or invasion of submucosal lymphatics or microvasculature (Fig. 16.26). Surgical resection (Fig. 16.27) is indicated following polypectomy if these histological features are noted, since there is a greatly increased risk of bowel wall invasion or lymphatic spread. Polypectomy may be technically impossible or the risk of perforation too high (caecal lesions) and so bowel resection may be indicated for larger polyps. Transanal endoscopic microsurgery (TEM) allows resection of large rectal villous adenomas and repair of the rectal defect using an operating microscope. Advanced colonoscopic techniques such as lasering or submucosal resection are now well established for larger lesions when surgery is to be avoided.

Fig. 16.26 Histological appearance of an adenomatous polyp, with malignant degeneration and early stalk invasion.

Fig. 16.27 Large adenoma of sigmoid colon resected endoscopically.

Follow-up colonoscopy is recommended after 6–12 months and 2–3 years. The current view is not in favour of long-term follow-up once the colon has been shown to be clear of any further polyps, unless the polyps fulfilled high-risk criteria or there were recurrent lesions at the 3-year screen.

Familial adenomatous polyposis (FAP)

FAP is one of the most common single-gene disorders predisposing to cancer and is inherited as an autosomal dominant trait. The gene responsible is APC, which is located on the long arm of chromosome 5. In addition to germline changes resulting in FAP, almost every sporadic colorectal cancer has a somatic defect in the APC gene or in other components of the W nt signalling pathway. The annual incidence of FAP is 1 in 6670 live births and the population prevalence is 1 in 13 528. Around 25% of affected individuals have no family history of FAP, the disease arising in these sporadic cases as the result of a new germline mutation. Direct testing for the APC gene is now routine. Clinicopathological diagnosis requires the presence of > 100 adenomatous polyps of the large bowel (Fig. 16.28). Adenomatous polyps usually develop during teenage years and early adulthood, with > 90% chance of colorectal cancer by the third or fourth decade if prophylactic colectomy is not undertaken. Because of effective surgical prophylaxis, FAP now accounts for less than 0.2% of all cases of colorectal cancer in the UK. The prevalence of colorectal cancer at diagnosis is 65% for symptomatic ‘sporadic’ cases and < 5% for screened family members, emphasizing the effectiveness of prophylaxis and surveillance.

Fig. 16.28 Macroscopic features of dense polyposis due to familial adenomatous polyposis.

Peutz–Jeghers syndrome (PJS)

PJS is a colorectal polyposis syndrome associated with a greatly increased risk of colorectal cancer and is discussed in the section on small intestinal disorders.

Juvenile polyposis syndrome (JPS)

Juvenile polyps are usually classified as hamartomas, although some regard them as inflammatory, with blockage of crypts resulting in retention cysts. Single juvenile polyps occur in around 1% of populations in developed countries, but juvenile polyposis is rare (estimated population frequency ∼︀1:50 000). JPS is an autosomal dominant genetic disorder characterized by the development of multiple hamartomatous polyps throughout the gastrointestinal tract, usually around age 10 years. Causal mutations of the SMAD4 or BMPR1A/ALK3 genes are responsible, indicating genetic heterogeneity. Penetrance is incomplete for polyposis and colorectal cancer. Estimates for gastrointestinal cancer risk range from 9% to 68%, but is probably ∼︀50% lifetime risk of colorectal cancer. In JPS families, or individuals with a documented SMAD4 or BMPR1A mutation, colonoscopic surveillance is recommended 1–2-yearly from the age of 15–18 years. Surveillance intervals can be extended after the age of 35 years. Documented gene carriers or affected cases should, however, be kept under surveillance until the age of 70 years. Consideration should be given to prophylactic colectomy, much in the same way as in FAP. While it is essential that cases are recognized and managed appropriately, because of its rarity < 0.1% of all cases of colorectal cancer are attributable to JPS.

Metaplastic (hyperplastic) polyposis and MUTYH-associated polyposis (MAP)

Metaplastic (now more properly termed as hyperplastic) polyps are usually less than 5 mm in diameter and occur in increasing numbers with age, being present in some 75% of the population over the age of 40 years. Polyps tend to be pale, flat-topped, sessile plaques, found mainly in the rectum and often on the crest of mucosal folds. Histologically, the crypts are elongated, dilated and lined by columnar epithelium that has a sawtooth pattern. These polyps are often indistinguishable from adenomatous polyps, and are frequently removed because of the difficulties in differentiating them from adenomas. Some of the larger metaplastic polyps take on the features of a serrated adenoma and principally affect the caecum, where they are highly likely to progress to cancer.

A subset of individuals with multiple hyperplastic polyps early in life has a substantially elevated cancer. A gene involved in DNA base excision repair (MUTYH) has been shown to be responsible for colorectal hyperplastic polyposis in association with adenomatous polyps. The syndrome should be considered as a differential diagnosis of FAP, but with smaller numbers of adenomas. Mode of inheritance is autosomal recessive (cf. FAP which is autosomal dominant) and colorectal cancer risk is very high. The management of documented homozygous MUTYH mutation carriers is controversial. Some advocate colonoscopic surveillance in the same manner as FAP and JPS but others cite the penetrance for colorectal cancer > 90% and recommend prophylactic colectomy and ileorectal anastomosis.

Other rare polyposis syndromes

Miscellaneous colorectal polyps

Benign lymphoid polyps are round, smooth and sessile tumours comprising aggregates of lymphoid tissue lined by attenuated epithelium varying in diameter from a few millimetres to 3 cm. Other differential diagnoses of colorectal polyps include pseudopolyps in chronic ulcerative colitis; submucosal lipoma; lymphosarcoma; carcinoid tumour; leiomyoma. Neurofibromatosis rarely results in colonic polyps. Mucosal ganglioneuromatosis has been described in association with multiple adenomatous or juvenile polyps and in MEN type IIb.

Colorectal adenocarcinoma

Adenocarcinoma of the large bowel is the most common gastrointestinal malignancy. It is second only to lung cancer as a cause of cancer death in developed countries. There are ∼︀36 000 new cases in the UK annually, accounting for around 15% and 12% of all cancer registration in males and females respectively. Lifetime risk is ∼︀5%. It is third-ranked cancer overall after lung and prostate in males, and breast and lung in females. The male:female ratio for colon cancer is close to unity, whereas that for rectal cancer is 1.7:1. Incidence rates increase substantially with age. The rectum and sigmoid are particularly common sites for tumours (Fig. 16.29). However, in low-incidence countries, tumours are more evenly distributed. Around 3% of patients present with synchronous tumours, and another 3% develop a metachronous tumour.

Fig. 16.29 Distribution of colorectal cancer in the large bowel in the UK.

Investigations

Colonoscopy is the investigation of choice (Fig. 16.30). However, increasingly CT colonography (Fig. 16.31) is employed in the investigation of altered bowel habit. It has similar diagnostic accuracy to colonoscopy, although clearly lacks the advantage of enabling diagnostic biopsy or snaring of adenomas. Barium enema (Fig. 16.32) still has a place but is becoming a somewhat obsolete test. Typical features of colorectal cancer are shouldering and mucosal destruction, but biopsy is essential wherever possible. In some instances the diagnosis is only made at laparotomy for a perforated or obstructed viscus.

Fig. 16.30 Typical colonoscopic features of colorectal cancer.

Fig. 16.31 CT showing a typical colorectal cancer with thickening, shouldering and mucosal ulceration.

Fig. 16.32 Barium enema showing a malignant ‘applecore’ appearance in the sigmoid colon, due to stenosing colorectal cancer.

Preoperative staging

Staging is a central component of preoperative work-up, as it provides important information on prognosis, helps inform surgical strategy and indicates the need or otherwise for adjuvant radiotherapy for rectal cancer and adjuvant postoperative chemotherapy for colorectal cancer. All patients with colon or rectal cancer should undergo CT of the chest, abdomen and pelvis (Fig. 16.33). Liver ultrasound and chest X-ray have now been almost totally superseded by CT. For rectal cancer, digital examination and rigid sigmoidoscopy should be undertaken in every case (examination under anaesthetic – EUA – may be required) to assess the degree of tumour fixity. Pelvic MRI is essential to assess the degree of local invasion of rectal cancer. Endoanal ultrasound may also be useful for local staging of rectal cancer, but is somewhat operator-dependent and requires considerable experience and interpretational skill. In some cases being considered for major debilitating surgery with a view to cure, FDG positron emission tomography in combination with CT scanning (FDG-PET-CT) is indicated. PET-CT has the potential to detect unsuspected distant metastatic disease that can influence the decision to undertake major resectional surgery, rather than more limited procedures.

Fig. 16.33 Rectal cancer imaging.

A CT features of early T₁ cancer (arrowed), restricted to the bowel wall. B Pelvic MRI showing T₃ cancer (arrowed), invading through the bowel wall and into the mesorectum.

Management of colorectal adenocarcinoma

Surgery

Elective colorectal resection with curative intent

The mainstay of treatment comprises en bloc resection of the primary tumour and loco-regional nodes. This achieves cure in 75% of cases undergoing intended ‘curative’ resections. Excision of the colonic mesentery, ligation of the arterial supply at its origin, and excision of all accompanying lymph nodes achieve locoregional lymphadenectomy for the respective segment of bowel (Fig. 16.34). Resection offers cure for patients with localized disease; even for patients with lymph node metastases but no distant metastases, cure can be expected in 50% of cases with surgery alone. For rectal cancer, excision of the entire mesorectum can reduce local recurrence rates to < 5%. Wherever possible, bowel continuity should be restored. In specialist hands, low rectal cancer should be treated by low anterior resection and colo-anal anastomosis. A colonic J-pouch may be formed in an attempt to improve defaecatory function. However, for low rectal cancer involving the sphincter muscle, it may be necessary to remove the anal sphincter as part of an abdominoperineal resection and fashion a permanent end-colostomy. Laparoscopic colorectal resection is increasingly used and has been shown to provide short-term benefits, with less pain and shorter hospital stay. However, there is no definitive evidence of improved long-term outcomes over open surgery.

Fig. 16.34 Surgical resection for colorectal cancer arising at various locations within the large bowel.

Radical tumour resection requires clearance of the primary tumour and also the arteries supplying that part of the colon. Lymphatic drainage follows the path of arterial supply, allowing a regional lymphadenectomy. A Excision of a right-sided tumour and the ileocaecal, right colic and right branch of middle colic arteries. B Tumours of transverse colon are usually treated by extended right hemicolectomy, again taking the feeding vessels at their origin from the superior mesenteric artery. C For left colonic lesions, the feeding vessels are taken. D Anterior resection is treated by high ligation of the inferior mesenteric artery.

Rectal cancer can be excised per-anally under direct vision or using trans-anal endoscopic microsurgery (TEM). TEM is particularly applicable to small low-lying cancers (< 3 cm). Per-anal excision has a place for T₁ or T₂ tumours and may allow avoidance of major abdominal surgery. However, careful staging is essential because the recurrence rate is 25–30% if there are incomplete excision margins or if the lesion was staged inaccurately. Pathology assessment may indicate the need to proceed to formal resection and mesorectal excision.

Early polyp cancers removed at colonoscopic snare polypectomy may be treated without the need for formal trans-abdominal resection. However, where the pathology specimen of the snared polyp cancer shows poor differentiation or submucosal lymphatic or vascular invasion, or where the diathermized margin is involved, formal resection and regional lymphadenectomy are indicated. With the introduction of population colorectal cancer screening by FOBT, this is becoming a more common scenario.

In the elective setting, the patient should be fasted and have undergone full preoperative work-up to assess cardiac, respiratory and any other co-morbidity; reversible risk factors for major surgery should have been addressed. Bowel preparation has been radically reshaped in recent years. Fluid diet is instigated for 48 hours prior to surgery but mechanical bowel preparation is now avoided for the majority of resections and only a phosphate enema 2 hours prior to surgery is required for left sided resections. Recent meta-analyses indicate that there is no benefit for mechanical bowel preparation (comprising polyethylene glycol, sodium picosulfate or phospho-soda), and it may even be harmful. However bowel preparation does have a place for low rectal anastomoses, especially if a defunctioning ileostomy is planned. Antibiotic prophylaxis comprises perioperative broad-spectrum antibiotics (e.g. a third-generation cephalosporin, or gentamicin and ampicillin, and metronidazole). Chemical thrombo-prophylaxis (low molecular weight fractionated heparin or calcium heparin), along with compression stockings and intraoperative intermittent pneumatic calf compression (EBM 16.5) is indicated as the risk of deep venous thrombosis and pulmonary embolism is high in such cases.

16.5 Preparation for surgery in patients with colorectal adenocarcinoma

‘Preoperative staging is required to guide surgery and pre-operative adjuvant radiotherapy.

Bowel preparation is not required for colorectal resection.

Compression stockings and heparin are required thromboprophylaxis for patients undergoing colorectal surgery.

Patient should be fasted prior to surgery.

Co-morbidity should be addressed wherever possible to limit perioperative mortality risk.

Perioperative antibiotic prophylaxis is essential and should cover coliform and anaerobic organisms.’

The Association of Coloproctology of Great Britain and Ireland. Guidelines for the Management of Colorectal Cancer 3rd edition (2007). http://www.acpgbi.org.uk/assets/documents/COLO_guides.pdf

Güenaga KF, Matos D, Wille-Jørgensen P. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD001544. DOI: 10.1002/14651858.CD001544.pub4.

Prevention and management of venous thromboembolism. Scottish Intercollegiate Guideline Network. http://www.sign.ac.uk/pdf/sign122.pdf

Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD001217. DOI: 10.1002/14651858.CD001217.

Antibiotic prophylaxis in surgery. Scottish Intercollegiate Guideline Network. http://www.sign.ac.uk/pdf/sign104.pdf

Nelson RL, Glenny AM, Song F. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001181. DOI: 10.1002/14651858.CD001181.pub3.

Emergency colorectal resection

In cases of perforation or obstruction of colorectal cancer, there is a substantially increased risk of perioperative mortality. The patient should be resuscitated before laparotomy is undertaken. For obstructed right-sided colon cancer, right hemicolectomy is the operation of choice. An ileo-transverse anastomosis can be safely performed, as the ileum has an excellent blood supply and the distal colon is not obstructed. Treatment of obstructed left colon cancer is best achieved by a one-stage resection with anastomosis whenever possible. Measures that may be employed to reduce the risk of anastomotic leakage in such cases include on-table colonic lavage to remove faecal residue. Resection of the entire colon and ileorectal anastomosis avoid a colocolic anastomosis and also remove any synchronous tumour (3% of cases). Patients with gross faecal peritonitis secondary to perforation of left colon cancer usually require resection with the creation of an end-colostomy (Hartmann’s procedure). If contamination is minimal, a specialist surgeon may elect to carry out primary resection and anastomosis. As in the elective setting, surgery should be covered with perioperative antibiotics and DVT prophylaxis.

Pathology and staging

Macroscopically, colorectal cancer may be polypoidal, ulcerating or stenosing (Fig. 16.35). Two-thirds are ulcerating and a typical lesion has raised everted edges, a slough-covered floor and indurated base. Tumours of the caecum tend to be large exophytic growths. Tumour differentiation may be classified as good, moderate or poor. Around 10–20% of tumours have mucinous histology and this tumour type has a poor prognosis. There is an increasing proportion of proximal tumours in the UK, as right colonic cancer is more common in the elderly and the UK population is ageing.

Fig. 16.35 Macroscopic characteristics of colorectal cancer.

A Stenosing. B Ulcerating. C Polypoidal.

Colorectal cancer may spread by lymphatic invasion, via the portal blood to the liver and/or by trans-peritoneal seeding. Once the peritoneum is breached, dissemination throughout the abdominal cavity is likely. Invasion of lymphatics results in regional lymph node involvement. Very low rectal tumours may also involve the inguinal nodes. Systemic metastases may occur in the later stages of the disease. Tumour staging systems include Dukes’ and TNM staging (Tables 16.7 and 16.8). TNM stages can be grouped using the American Joint Committee on Cancer (AJCC) system (Table 16.9). Pathological staging has important implications for prognosis and also for directing clinical management (EBM 16.6). Staging information informs both predicted survival outcome and also decision-making on whether adjuvant chemotherapy is indicated.

Table 16.7 Dukes’ staging for colorectal cancer

Dukes’ stage	Description	Proportion of colorectal cancers (%)
A	Spread into, but not beyond, muscularis propria	10
B	Spread through full thickness of bowel wall	30
C	Spread to involve lymph nodes	30
D*	Distant metastases	20

* There is formally no D stage in Dukes’ staging; this is a misnomer, as Dukes’ staging refers only to degree of local invasion and to lymphatic spread. However, the term is widely used in clinical practice.

Table 16.8 TNM staging of colorectal cancer

T (Tumour)

• Tx

Primary tumour cannot be assessed

• Tis

Radiotherapy

Adjuvant preoperative radiotherapy has an important place in the management of rectal cancer, and so preoperative staging of rectal cancer is essential in order to plan optimal management. Radiotherapy has been shown to reduce local recurrence rates but there is no effect on overall survival (EBM 16.6). Most specialist centres in the UK offer selective preoperative radiotherapy for those at increased risk of local recurrence, because there is significant morbidity associated with pelvic irradiation and many patients will be cured by surgery alone. Risk factors include a low tumour, bulky fixed lesion, anterior lesion, evidence of T₃ or T₄ stage and/or involved lymph nodes on imaging. Either a 5-day short-course regimen of 45 Gy daily or a long-course regimen of 52 Gy given weekly over 3 months is administered. The former is reserved for patients with operable but tethered tumours or very low or anterior tumours, or if extra-rectal spread is evident. Fixed, inoperable tumours are best dealt with by radical radiotherapy over 3 months, and this may be combined with chemotherapy (capecitabine or 5-fluorouracil (5-FU)). Postoperative radiotherapy results in poor bowel function and may damage the small intestine, and hence the importance of preoperative staging to guide administration of radiotherapy before surgery whenever possible.

Adjuvant chemotherapy

Systemic adjuvant chemotherapy using 5-FU alone or in combination with other agents has been shown to improve survival for Dukes’ C colorectal cancer after surgical resection (EBM 16.6). Intravenous regimens employing intravenous 5-FU has largely been replaced in current practice by targeting the same pathway through inhibition of thymidylate synthase using chemical inhibitors such as capecitabine. Capecitabine is less toxic than 5-FU and can be administered orally. There is an overall 30% improvement in survival for patients with Dukes’ C tumours who receive chemotherapy, equating with an 11% absolute improvement in survival for that group and a 6% overall improvement in survival for patients with colorectal cancer of all stages. In the UK, it is now routine practice to offer chemotherapy based on 5-FU to all patients with stage C cancers who do not have significant comorbidity, particularly cardiovascular disease. Regimens now routinely combine capecitabine with oxaliplatin as first line therapy. Recently, it has also been shown that Dukes’ B tumours gain modest survival benefit (∼︀2%). However, adjuvant chemotherapy for Dukes’ B tumours is restricted to poor-prognosis lesions (poor differentiation, venous or lymphatic invasion). Capecitabine (or 5-FU) chemotherapy is considered a conventional ‘first-line’ chemotherapeutic regimen for colorectal cancer. Other newer agents, such as cetuximab (monoclonal antibody to epidermal growth factor receptor) and bevacizumab (antibody to vascular endothelial growth factor), have shown promise in patients with relapsed disease after first-line chemotherapy. Other agents such as temozolomide, used either alone or in combination with other standard agents are also used in relapsed disease and in trials. Although irinotecan (CPT-11) showed initial promise, a number of negative trials indicate it may only have a place in the management of a small selected subset of patients.

Squamous cancer of the large bowel

Such tumours are not simply metastatic anal carcinomas, but may arise in the caecum and proximal colon from an area of squamous metaplasia in long-standing ulcerative colitis. In the absence of chronic inflammation, an adenosquamous pattern may be seen and the prognosis is poor.

Carcinoid tumour of the large bowel

Large bowel carcinoid tumours are very rare, but benign lesions may be found incidentally during rectal examination as solitary, spherical, hard, sessile, yellowish submucosal nodules. Malignant carcinoid tumors of the colon are frequently highly malignant and may give rise to the carcinoid syndrome. Around 60% have metastasized by the time of diagnosis.

Lymphoma of the large intestine

Primary lymphomas usually arise in the rectum or caecum but are occasionally multicentric. Secondary involvement of the large bowel in generalized disease is more common. Barium enema shows a long rigid segment with intramural thickening. The diagnosis is established by endoscopic or operative biopsy. Primary lymphomas are treated by resection, followed by chemotherapy and radiotherapy. Secondary malignant lymphoma and malignant lymphomatous polyposis are treated by systemic chemotherapy and targeted radiotherapy.

Gastrointestinal stromal tumours (including leiomyosarcoma)

These tumours are rare in the large bowel and are discussed above with respect to the small bowel. They arise from the muscle of the bowel wall, most usually the rectum, and are usually diagnosed by digital examination or by sigmoidoscopy. As discussed, there is a spectrum from benign to malignant and the tumours are often impossible to distinguish clinically; resection is therefore advisable. Metastases occur via the bloodstream to the liver and lungs.