Category Archives: Gastroenterology

Investigative tests can be divided into:
1 Blood tests
(a) Liver ‘function’ tests
(i) Serum albumin
(ii) Prothrombin time
(b) Liver biochemistry
(i) Reflecting hepatocellular damage-serum aspartate and alanine aminotransferases
(ii) Reflecting cholestasis-serum alkaline phosphatase, y-glutamyl transpeptidase
(c) Viral markers
(d) Additional blood investigations, e.g. autoantibodies
2 Imaging techniques-to define gross anatomy
3 Liver biopsy-for histology
Most routine ‘liver function tests’ sent to the laboratory will be processed by an automated multichannel analyser to produce serum levels of bilirubin, aminotransferases, alkaline phosphatase, y-glutamyl transpeptidase (yG T) and serum proteins. These routine tests are markers of liver damage but not actual tests of ‘function’ per se. Subsequent investigations are often based on these tests.

Blood tests

Liver function tests

SERUM ALB UMIN. This is a marker of synthetic function and is a valuable guide to the severity of chronic liver disease. A falling serum albumin in liver disease is a bad prognostic sign. In acute liver disease initial albumin levels may be normal.

PROTHROMBIN TIME (PT). This is also a marker of synthetic function. Because of its short half-life it is a sensitive indicator of both acute and chronic liver disease. Vitamin K deficiency should be excluded as the cause of a prolonged PT by giving an intravenous bolus (10 mg) of vitamin K. Vitamin K deficiency commonly occurs in biliary obstruction, as the low intestinal concentration of bile salts results in poor absorption of vitamin K. Liver biochemistry BILIRUBIN. In the serum, bilirubin is normally almost all unconjugated. In liver disease increased serum bilirubin is usually accompanied by other abnormalities in liver biochemistry. Determination of whether the bilirubin is conjugated or unconjugated is only necessary in congenital disorders of bilirubin metabolism  or to exclude haemolysis.
AMINOTRANSFERASES. These enzymes (often referred to as transaminases) are present in hepatocytes and leak into the blood with liver cell damage. The two enzymes measured are:
1 Aspartate aminotransferase (AST), which was previously known as serum glutamic oxaloacetic transaminase (SGOT). This is a mitochondrial enzyme and is also present in heart, muscle, kidney and brain. High levels are seen in hepatic necrosis, myocardial infarction, muscle injury and congestive cardiac failure.
2 Alanine aminotransferase (ALT), which was previously known as serum glutamic pyruvic transaminase (SGPT). This is a cytosol enzyme and is more specific to the liver than AST.
ALKALINE PHOSPHATASE (AP). This is present in the canalicular and sinusoidal membranes of the liver, but is also present in many other tissues, e.g. bone, intestine and placenta. If necessary, its origin can be determined by electrophoretic separation of isoenzymes or, alternatively, if there is also an abnormality of, for example, the ‘YGT, the AP can be presumed to come from the liver.
Serum AP is raised in cholestasis from any cause, whether intrahepatic or extrahepatic disease. The synthesis of AP is increased and this is released into the blood. In cholestatic jaundice, levels may be up to four to six times the normal limit. Raised levels may also occur in conditions with infiltration of the liver, e.g. metastases, and in cirrhosis, frequently in the absence of jaundice.
The highest serum levels due to liver disease (>1000 IU litre “) are seen with hepatic metastases and primary biliary cirrhosis.
‘Y-GLUTAMYL TRANSPEPTIDASE. This is a microsomal enzyme that is present in many tissues as well as the liver. Its activity can be induced by such drugs as phenytoin and by alcohol. If the AP is normal, a raised serum ‘YGT is a good guide to alcohol intake and can be used as a screening test . Mild elevation of the ‘YGT is common even with a small alcohol consumption and does not necessarily indicate liver disease if the other liver biochemical tests are normal. In cholestasis the ‘YGTrises in parallel with the AP as it has a similar pathway of excretion. This is also true of the 5-nucleotidase, another microsomal enzyme that can be measured in blood. SERUM PROTEINS. Serum albumin is discussed above.
Hyperglobulinaemia occurs in chronic liver disease. This is thought to be due to reduced phagocytosis by sinusoidal and Kupffer cells of the antigens absorbed from the gut, which then stimulate antibody production in the spleen and lymph nodes. In chronic liver disease, immunoglobulins are formed by lymphoid and plasma cells that infiltrate the portal tracts. The routine plasma electrophoretic strips contain immunoglobulins in the f3 and ‘Yregions. In cirrhosis there is f3-1’ fusion due to an increase in the faster-moving globulins; the diagnostic value of these strips is, however, limited. In primary biliary cirrhosis the predominant serum immunoglobulin that is raised is IgM, and in autoimmune chronic active hepatitis it is IgG.

Viral markers

These are available for most of the common viruses that cause hepatitis

ADDITIONAL BLOOD INVESTIGATIONS

lIaematologicaI

A full blood count is always performed. Anaemia may be present. The red cells are often macrocytic and can have abnormal shapes-target cells and spur cells-owing to membrane abnormalities. Vitamin BI2 levels are normal or high, and folate levels are often low owing to poor dietary intake. Other changes are caused by the following:
• Bleeding produces a hypochromic, microcytic picture
• Alcohol causes macrocytosis, sometimes with leucopenia and thrombocytopenia
• Hypersplenism results in pancytopenia
• Cholestasis can often produce abnormal-shaped cells and also deficiency of vitamin K
• Haemolysis accompanies acute liver failure and jaundice
• Aplastic anaemia is present in up to 2% of patients with acute viral hepatitis
• Serum ferritin and transferrin saturation Biochemical
aI-ANTITRYPSIN. A deficiency of this enzyme can produce cirrhosis.
a- FETOPROTEIN. This is normally produced by the fetal liver. Its reappearance in increasing and high concentrations in the adult indicates hepatocellular carcinoma. Increased concentrations in pregnancy in the blood and amniotic fluid suggest neural-tube defects of the fetus. Blood levels are also slightly raised in patients with hepatitis, chronic liver disease and also in teratomas.

Immunological tests

There are no specific antibodies to the liver itself that are routinely measured. Autoantibodies found are:
ANTIMITOCHONDRIAL ANTIBODY (AMA) is found in the serum in over 95% of patients with primary biliary cirrhosis (see p. 268). Many different AMA subtypes have been described, depending on their antigen specificity. AMA is demonstrated by an immunofluorescent technique and is neither organ nor species specific.
Some subtypes are occasionally found in autoimmune chronic active hepatitis and other autoimmune diseases.
NUCLEIC, SMOOTH MUSCLE (ACTIN), LIVER/KIDNEY MICROSOMALANTIBODIES can be found in the serum in high titre in patients with autoimmune chronic active hepatitis. These antibodies can be found in the serum in other autoimmune conditions and other liver diseases.

Bromsulphthalein (BSP) clearance test

This is now very rarely performed. The liver normally clears BSP from the blood. The level of BSP in the blood after an intravenous injection of BSP is a sensitive guide to hepatocellular damage. A second recirculation peak occurs in the congenital hyperbilirubinaemia of the Dubin-Johnson syndrome. Anaphylactic reactions may occur.
Useful blood tests for certain liver diseases are shown.

The peritoneal cavity is a closed sac lined by mesothelium. It normally contains a little fluid that allows the intra-abdominal organs to move freely. Some conditions that can affect the peritoneum are shown . Peritonitis can be acute or chronic, as seen in TB. Most cases of infective peritonitis are secondary to gastrointestinal diseases but it occasionally occurs without intraabdominal sepsis in ascites due to liver disease. Very rarely, fungal and parasitic infections can also cause primary peritonitis, e.g. amoebiasis, candidiasis. Peritonitis is discussed further. The peritoneum can be involved by secondary malignant deposits and the commonest cause of ascites in a young to middle-aged woman is an ovarian carcinoma.

A subphrenic abscess is usually secondary to infection in the abdomen and is characterized by fever, malaise, pain in the right or left hypochondrium and shouldertip pain. A plain abdominal X-ray shows gas under the diaphragm, impaired movement of the diaphragm on screening and a pleural effusion. Ultrasound is usually diagnostic.
Ascites is associated with all diseases of the peritoneum. The fluid that collects is an exudate with a high protein content. It is also seen in liver disease. The mechanism, causes and investigation of ascites are discussed.

Tuberculous peritonitis

This is due to reactivation of a tuberculous focus in the abdomen, often a lymph node. It is common in developing countries and is seen in the UK in debilitated patients, alcohol-dependent patients and in certain racial groups, e.g. Asians. Usually the onset is insidious, with fever, anorexia and weight loss. Abdominal pain is common, accompanied by ascites (75%) or an abdominal mass caused by an inflamed mesentery. Diagnosis is made by examination of the peritoneal fluid, if present, which shows an increase in lymphocyte count; occasionally tubercle bacilli are seen on staining. Culture of the fluid should be performed. Ultrasound shows mesenteric thickening and enlargement of lymph nodes. At laparoscopy the peritoneum is seen to be studded with tubercles that can be biopsied and sent for culture and histology. Treatment is with conventional chemotherapy for 18 months to 2 years.

Retroperitoneal fibrosis

This is a rare condition in which there is a marked fibrosis over the posterior abdominal wall and retroperitoneum. The aetiology is usually unknown but it has been associated with the drug methysergide and occasionally with the carcinoid syndrome. The disease usually presents in middle age with malaise, fever and loss of weight. There is often anaemia and a raised ESR-a CT scan is diagnostic.
The major complication is urinary tract obstruction from ureteric involvement, which may require surgery. Further reading Bailliere’s Clinical Gastroenterology-quarterly reviews of gastroenterology. London: Bailliere Tindall. Field M et al. (1989) Intestinal electrolyte transport and diarrhoeal disease. New England Journal of Medicine, 321, 879.
Gastroenterology Clinics of North America (1993), 22.
Review articles on H. pylori infection.
Lynch HT et al. (1993) Genetics, natural history, tumour spectrum and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104, 1535.
Sleisenger MH & Fordtran JS (1993) Gastrointestinal Disease:
Pathophysiology, Diagnosis, Management, 5th edn.
Philadelphia: WB Saunders.

Most intestinal obstruction is due to a mechanical block. Sometimes the bowel does not function, leading to a paralytic ileus. This occurs temporarily after most abdominal operations and with peritonitis. Some causes of intestinal obstruction are shown. Obstruction of the bowel leads to bowel distension above the block, with increased secretion of fluid into the distended bowel. Bacterial contamination occurs in the distended stagnant bowel. In strangulation the blood supply is impeded, leading to gangrene, perforation and peritonitis unless urgent treatment of the condition is undertaken.

CLINICAL FEATURES

The patient complains of colicky abdominal pain, vomiting and constipation without passage of wind. In upper gut obstruction the vomiting is profuse but in lower gut obstruction it may be absent. Examination of the abdomen reveals distension with increased bowel sounds. Marked tenderness suggests strangulation and urgent surgery is necessary. Examination of the hernial orifices and rectum must be performed.
X-ray of the abdomen reveals distended loops of bowel proximal to the obstruction. Fluid levels are seen in small bowel obstruction on an erect film. In large bowel obstruction, the caecum and ascending colon are distended. A water-soluble barium enema may help to demonstrate the site of the obstruction.

MANAGEMENT

Initial management is by nasogastric intubation to decompress the bowel and replacement of fluid loss by intravenous fluids (mainly isotonic saline). Laparotomy with removal of the obstruction is necessary in most cases of small bowel obstruction and if the bowel is gangrenous owing to strangulation gut resection will be required. A few patients, e.g. those with Crohn’s disease, may have recurrent episodes of subacute intestinal obstruction that can be managed conservatively. Large bowel obstruction can often be managed conservatively with a defunctioning colostomy being performed, if necessary. Volvulus of the sigmoid colon can be managed by the passage of a rectal tube to unkink the bowel, but recurrent volvulus may require sigmoid resection.

Rarely the clinical features of obstruction are produced by a condition in which the nerve plexuses of the bowel are damaged – intestinal pseudo-obstruction. This condition is managed conservatively.

Acute intestinal ischaemia

Mesenteric artery occlusion, either from an embolus or from thrombosis in an arteriosclerotic artery, leads to gut ischaemia and, if not dealt with promptly, necrosis of the intestine. The patient presents with severe abdominal pain and vomiting. Bloody diarrhoea is a helpful indicator of the diagnosis but does not occur for some time. The abdomen is usually tender and bowel sounds are absent. The diagnosis must be considered in any elderly patient with arteriosclerotic disease or in patients with atrial fibrillation. Early surgery may prevent gut necrosis but sometimes massive resection of the dead gut is required to save the patient’s life. Mesenteric venous thrombosis occurs mainly in patients who have circulatory failure and can lead to gut necrosis. Often the patient is extremely ill from the underlying condition but surgery may be necessary if the patient is fit enough.

This section deals with acute abdominal conditions that cause the patient to be hospitalized within a few hours of the onset of their pain. It is important to make the diagnosis as quickly as possible to reduce morbidity and mortality. Although a specific diagnosis should be attempted, the immediate problem in management is to decide whether an ‘acute abdomen’ exists and whether surgery is required.

History

This should include previous operations, any gynaecological problems and whether any concurrent medical condition is prsent.

Pain

The onset, site, type and subsequent course of the pain should be determined as accurately as possible. ‘Visceral’ pain due to distension of a viscus or stretching of a capsule is poorly localized. However, in general, upper abdominal pain is produced by upper gastrointestinal tract lesions and lower abdominal pain by lesions of the lower gastrointestinal tract. Localized pain in the right iliac fossa suggests acute appendicitis.

Sudden pain suggests:
• A perforation, e.g. of a duodenal ulcer
• A rupture, e.g. of an aneurysm
• Torsion, e.g. of an ovarian cyst
• Acute pancreatitis Back pain suggests:
• Pancreatitis
• Rupture of an aortic aneurysm
• Renal tract disease
Inflammatory conditions, e.g. appendicitis, produce a more gradual onset of pain while in intestinal obstruction the pain is typically colic in nature. With peritonitis the pain is continuous and may be made worse by movement.

Vomiting

Vomiting may accompany any acute abdominal pain, but if persistent it suggests an obstructive lesion of the gut. The character of the vomit should be asked – does it contain blood, bile or small bowel contents?

Other symptoms

Any change in bowel habit or of urinary frequency should be documented and, in females, a gynaecological history taken.

Physical examination

The general condition of the patient should be noted. Does he or she look ill? Is the patient shocked? Large volumes of fluid may be lost from the vascular compartment into the peritoneal cavity or into the lumen of the bowel giving rise to hypovolaemia, a pale cold skin, a weak rapid pulse and hypotension.

Abdomen

INSPECTION. Look for the presence of scars, distension or masses.
PALPATION. The abdomen should be examined gently for sites of tenderness and the presence or absence of guarding. Guarding is involuntary spasm of the abdominal wall and it indicates peritonitis. This can be localized to one area or it may be generalized, involving the whole abdomen.
BOWEL SOUNDS. Increased high-pitch tinkling bowel sounds indicate obstruction; this occurs because of fluid movement within the large dilated bowel lumen. Absent bowel sounds suggest peritoneal involvement. In an obstructed patient, absent bowel sounds suggest strangulation or ischaemia.
It is essential that the hernial orifices are examined if intestinal obstruction is suspected. Pelvic and rectal examination. These can be very helpful, particularly in diagnosing gynaecological causes of an acute abdomen, e.g. a ruptured ectopic pregnancy. Rectal examination may detect localized tenderness or blood in the stools, which is suggestive of a vascular lesion.

Other observations

1 Mouth-the tongue is furred in most acute abdominal disease and a fetor is present.
2 Temperature-fever is more common in acute inflammatory processes.
3 Urine-examine for:
(a) Blood-suggests urinary tract infection or renal colic.
(b) Glucose and ketones-ketoacidosis can present with acute pain.
(c) Protein and white cells (to exclude acute pyelonephritis).
4 Think of other conditions, e.g.
(a) Diabetes mellitus (ketoacidosis).
(b) Pneumonia (referred pain).
(c) Myocardial infarction (referred pain).
(d) Lead poisoning.
(e) The irritable bowel syndrome (this can produce acute severe pain).
(f) Renal colic.
(g) Porphyria is a rare cause of abdominal pain.

Investigation

BLOOD COUNT A raised white cell count occurs with inflammatory conditions.

SERUM AMYLASE High levels of greater than five times normal indicate acute pancreatitis. Raised levels below this can occur in any acute abdomen and should not be considered diagnostic of pancreatitis.
SERUM ELECTROLYTES are not particularly helpful for diagnosis, but useful for general evaluation of the patient. X-RAY OF THE ABDOMEN. Chest and supine X-rays of the abdomen are useful to detect air under the diaphragm (perforation) or dilated loops of bowel or fluid levels suggestive of obstruction.
ULTRASOUND-is useful in the diagnosis of acute cholangitis and in good hands is reliable in the diagnosis of acute appendicitis. Gynaecological and other pelvic causes of pain can also be detected.
LAPAROSCOPy-is being increasingly used in the diagnosis of the acute abdomen when, in addition, therapeutic manoeuvres, such as appendicectomy, can be performed.

SPECIFIC CONDITIONS

Acute appendicitis

This is the commonest surgical emergency. It affects all age groups, but is rare in the very young and the very old. Appendicitis should always be considered in the differential diagnosis if the appendix has not been removed. Acute appendicitis mostly occurs when the lumen of the appendix becomes obstructed with a faecolith; however, in some cases there is only generalized acute inflammation. If the appendix is not removed at this stage, gangrene occurs with perforation, leading to a localized abscess or to generalized peritonitis.

CLINICAL FEATURES AND MANAGEMENT

Most patients present with abdominal pain; in many it starts vaguely in the centre of the abdomen, becoming localized to the right iliac fossa in the first few hours. There is nausea, some vomiting and occasional diarrhoea. Because of the variable position of the appendix, symptoms and signs differ.
Examination of the abdomen reveals tenderness in the right iliac fossa, with guarding due to the localized peritonitis. Rectal examination may reveal tenderness to the right. There may be a tender mass in the right iliac fossa. Laboratory tests are unhelpful, except that the white cell count may be raised. An ultrasound is accurate for the detection of an inflamed appendix and will also indicate an appendix mass or other localized lesion. In the differential diagnosis all abdominal conditions must be considered, including:
• Non-specific mesenteric lymphadenitis may mimic appendicitis.
• Acute terminal ileitis (see p. 216) -due to Crohn’s disease;
Yersinia infection also gives similar symptoms and signs.
• Acute salpingitis-should be considered in women.
There is usually a vaginal discharge and on vaginal examination adnexal tenderness is found.

• Inflamed Meckel’s diverticulum.
• Functional bowel disease.

TREATMENT

The appendix is removed by open surgery or laparoscopically. If an appendix mass is present, the patient is treated conservatively with antibiotics. The pain subsides over a few days and the mass usually disappears over a few weeks. Appendicectomy is recommended at a later date to prevent further acute episodes.

Acute peritonitis

Localized peritonitis

There is virtually always some degree of localized peritonitis with all acute inflammatory conditions of the gastrointestinal tract, e.g. acute appendicitis, acute cholecystitis. Pain and tenderness are largely features of this localized peritonitis. The treatment is for the underlying disease.

Generalized peritonitis

This is a serious condition resulting from irritation of the peritoneum due to infection, e.g. perforated appendix, or from chemical irritation due to leakage of intestinal contents, e.g. perforated ulcer. In the latter case, superadded infection gradually occurs; E. coli and Bacteroides are the commonest organisms. The peritoneal cavity becomes acutely inflamed with production of an inflammatory exudate that spreads throughout the peritoneum leading to intestinal dilatation and paralytic ileus.

CLINICAL FEATURES AND MANAGEMENT

In perforation the onset is sudden with acute severe  bdominal pain, followed by general collapse and shock. The patient may improve temporarily, only to become worse later as generalized toxaemia occurs. When the peritonitis is secondary to inflammatory disease, the onset is less rapid with the initial features being those of the underlying disease. Investigations should always include an abdominal Xray to detect free air under the diaphragm and a serum amylase to diagnose acute pancreatitis, which is treated conservatively.
Peritonitis is always treated surgically after initial treatment of the patient’s general condition, including insertion of a nasogastric tube, intravenous fluids and antibiotics. Surgery has a two-fold objective:
1 Drainage of the abdominal cavity
2 Specific treatment of the underlying condition

COMPLICATIONS

Any delay in treatment of peritonitis produces more profound toxaemia and septicaemia. In addition, local abscess formation occurs and should be suspected if the patient continues to remain unwell postoperatively with a swinging fever, high white cell count and continuing pain. Abscesses are commonly pelvic or subphrenic. Both are now localized chiefly by ultrasound examination;
treatment is with antibiotics and drainage is often required.

This is the general term used to embrace two syndromes:
1 Non-ulcer dyspepsia
2 The irritable bowel syndrome
These conditions are extremely common worldwide, making up to 60-80% of patients seen in a gastroenterology clinic. The two conditions overlap, with some symptoms being common to both. gives some gastrointestinal symptoms that are suggestive of psychosomatic disorders.

Non-ulcer dyspepsia

This consists of a heterogeneous group of patients whose symptoms are mainly stress-related. Patients complain of indigestion, wind, nausea, early satiety, heartburn, i.e. dyspepsia, when no ulcer is found. It can be difficult on the history to differentiate it from the symptoms of peptic ulceration, but typically patients with ulcers have nocturnal pain and also respond to antacids. Barium studies or endoscopy are often performed to exclude ulceration, but are best avoided in patients under 35 years, as no abnormality is found in the majority (80%). Chronic active gastritis due to H. pylori is found more frequently than in asymptomatic controls, but the relationship of this finding with symptoms is unclear.
Treatment is by reassurance. Antacids and Hz-receptor antagonists are probably of little benefit apart from the placebo effect. Cisapride 10 mg three times daily and metoclopramide 10 mg three times daily sometimes help particularly in the patients with fullness and early satiety, some of whom have been shown to have slow gastric emptying. The irritable bowel syndrome.

CLINICAL FEATURES

The pain is classically situated in the left iliac fossa and is usually relieved by defecation or the passage of wind. The patient may complain of constipation or diarrhoea with the passage of frequent small-volume stools and a feeling of incomplete emptying of the rectum. Stools may be ribbon-like or rabbity in appearance. True watery diarrhoea suggests organic disease. The pain, however, can be very variable and occur in any part of the abdomen and the bowel habit may be normal.

Abdominal distension and bloating are extremely common and if present strongly suggest the diagnosis of the irritable bowel. Women are more frequently affected than men, and often the symptoms occur at the time of the period. The length of history is usually long with frequent recurrent episodes and long symptom-free intervals. The patient may give a history of recurrent episodes of abdominal pain as a child and there is an increase of childhood or sexual abuse in some series. Mild episodes of pain occur frequently (approximately 40%) in the normal population and are often disregarded. The reason why some patients attend doctors is unclear, but it is sometimes related to other social factors. The patient with the irritable bowel syndrome looks well despite frequent episodes of pain, some of which can be very a cute and require hospital admission to rule out an acute abdominal condition.

PATHOPHYSIOLOGY

Motility abnormalities have been found in the irritable bowel syndrome, but these abnormal findings have not been consistent and do not always correlate with episodes of pain.
Psychological factors are important and most patients find the symptoms are exacerbated by stress. Some patients are depressed, and this fact may be missed unless carefully looked for.

EXAMINATION

Examination reveals no abnormality. Rectal examination and sigmoidoscopy should be performed. Although sigmoidoscopy shows a normal mucosa, air insufflation may reproduce the pain. If diarrhoea is a feature, a rectal biopsy should be performed, even if the mucosa looks normal, to help rule out inflammatory bowel disease.

INVESTIGATION

The amount of investigation varies in individual patients. A young girl with pain in the left iliac fossa exacerbated by stress will require no investigation. Conversely, an elderly person who has developed pain or diarrhoea for the first time must be investigated, with a full radiological assessment, before the diagnosis of functional bowel disease is made.

MANAGEMENT

In many patients symptoms are not severe and are clearly stress-related. These patients often require nothing but a discussion of their life-style and reassurance. Over-investigation (Information box 4.6) and drug therapy should be avoided.
• Patients must be reassured of the benign nature of the condition. Cancer phobia must be dispelled. Patients are encouraged to learn to cope with their symptoms, as they tend to be recurrent.
• A high-fibre diet or even a change in diet help some patients.

• Antispasmodics, e.g. mebeverine, are given.
• A small group of patients who are often hospital attenders have severe symptoms and treatment here is difficult. Many are depressed and improve with antidepressant therapy. Other therapies, i.e. biofeedback and hypnotherapy, have been tried.

Adenocarcinoma of the large bowel is the second commonest tumour in the UK with a lifetime incidence of about 1 in 50 (both male and female). The incidence increases with age, the average age at diagnosis being 60-65 years. The disease is rare in Africa and Asia and this difference is thought to be largely environmental rather than racial. There is a correlation between the consumption of meat and animal fat and colonic cancer. Western diets are low  in fibre and the resulting intestinal stasis increases the time for which any potential carcinogen is in contact with the bowel wall. The bacterial flora in the colon is also affected by different diets, particularly in amount of fibre present, and it is speculated that certain bacteria convert bile acids to potential carcinogens. Ulcerative colitis and FAP are predisposing factors.

GENETIC INHERITANCE

The development of colon cancer is now felt to involve multiple genetic alterations which occur in a stepwise fashion. The widespread recognition of the adenoma-carcinoma sequence and the identification of many molecular genetic abnormalities has led to the development of a molecular model for colon cancer tumorigenesis . The changes include the activation of dominantly acting proto-oncogenes and the inactivation of recessive tumour suppressive genes. Oncogenes, many of which have a physiological role in the regulation of normal cell division and differentiation, may result in inappropriate stimulation signals. Those most commonly associated with colon cancer are c-KRAS and c-MYC which are overexpressed in up to 50% and 70% of colon tumours respectively. Other less frequently altered oncogenes include c-SRC, c-MYB and c-ERB-2. Tumour suppressor genes conversely inhibit cell proliferation and tumorigenesis.
Mutations of the ape gene located on the long arm of chromosome 5 is responsible for the FAP syndrome, but also plays a role in sporadic colon cancer. It appears, however, that the accumulation rather than the order of changes is most important in tumour development.

Cancer families

There is a two to three times increased lifetime risk of developing colon cancer with one first-degree affected family member. Hereditary non-polyposis colon cancer (HNPCC) occurs in 5-10% of colorectal cancers. The putative gene responsible has recently been localized on chromosome 2. These patients have tumours at an early age and, more commonly, in the right colon. Many of these patients also have a high risk of endometrial and other non-gastrointestinal cancers (Lynch type II) whilst others are colon specific (Lynch type I).

Screening

The case for universal faecal occult blood screening has been made with a reduction of the 13-year cumulative mortality by 33%. It is not yet recommended in the UK. A single, flexible sigmoidoscopy at the age of 55 years or over is being recommended by some as another screening method. Universal colonoscopic screening has not shown any benefit, but colonoscopy should be performed in anyone with a history of cancer in their first- and seconddegree relatives. Measurement of DNA in the stools is also being developed for screening.

PATHOLOGY

Two-thirds of carcinomas occur in the rectosigmoid area. The tumour, which is usually a polypoid mass with ulceration, spreads by direct infiltration through the bowel wall. It then invades the lymphatics and blood vessels with early spread to the liver. Widespread metastases, e.g. to the lung, can occur. Synchronous tumours are present in 2% of cases.

CLINICAL FEATURES

Alteration in bowel habit, with or without abdominal pain, is a common symptom of left-sided colonic lesions. Rectum and sigmoid carcinomas usually bleed, blood being mixed in with the stool. Carcinoma of the caecum may become large and still remain asymptomatic. It can present simply as an iron deficiency anaemia. The elderly often present with intestinal obstruction. Any change in bowel habit or bleeding per rectum must be investigated, particularly in the older age group.
Clinical examination is usually unhelpful, but a mass may be palpable. With liver metastases, hepatomegaly is found. Digital examination of the rectum is essential and sigmoidoscopy should be performed in all cases. Fibreoptic sigmoidoscopy can be performed on an outpatient basis after a single enema and increases, by three to four times, the extent of the colon seen covering the area with the highest risk of carcinoma.

INVESTIGATION

A BLOOD COUNT and routine biochemistry are performed.
A DOUBLE-CONTRAST BARIUM ENEMA is still the investigation of choice but good preparation to ensure that the colon is free of faeces is essential.

COLONOSCOPY is used for confirmation of doubtful lesions and to obtain specimens for histological examination.
OCCULT BLOOD TESTS have been used for mass screening but are of no value in hospital practice.
ULTRASOUND. Evaluation of secondary spread is performed prior to surgery with abdominal ultrasound and rectal ultrasound, which is valuable to indicate tumour size and local spread.

TREATMENT

This is surgical, with resection and end-to-end anastomosis if possible. Anastomosis is now possible with all but the most distal rectal carcinomas, when colostomy is necessary. The 5-year survival rate is 30% overall, but in tumours confined to the bowel wall (i.e. not reaching the serosa-Dukes’ grade A), the 5-year survival is over 95% . Adjuvant chemotherapy increases survival in Dukes’ grade Band C. Adjuvant chemotherapy and radiotherapy increase survival in grade C rectal carcinoma. Chemotherapy is sometimes used when metastases are present, but results are poor.

These important conditions largely present to surgeons. The major conditions presenting initially to the physician include the following.

Pruritus ani

Pruritus ani, or an itchy bottom, is common and often no cause is found. Treatment consists of good personal hygiene and keeping the area dry. Secondary causes include any local anal lesions such as haemorrhoids, infestation, e.g. with threadworm (Enterobius vermicularis), or fungal infection, e.g. candidiasis. The latter condition often occurs secondary to the use ofhydrocortisone creams, which should be avoided.

Haemorrhoids

Haemorrhoids usually produce rectal bleeding and pruritus ani. Patients may notice red blood on the toilet paper on wiping. They are the commonest cause of rectal bleeding and if minor, require no treatment. Diagnosis is made on proctoscopy.

Anal fissures

Anal fissures cause painful defecation and minor rectal bleeding and can often be seen in the anal margin on inspection. Treatment is by application of a local anaesthetic gel. Dilatation is not required.

Faecal incontinence

This can be a major problem in the elderly, infirm or demented patient. It is often secondary to impaction. Some of the major factors responsible are rectal prolapse, carcinoma of the rectum and diarrhoea from any cause. The patient should be carefully examined and investigation and treatment instituted as appropriate.

Faecal impaction

This occurs in the elderly with constipation. It can lead to overflow incontinence. It usually requires manual removal of faeces, and care to prevent recurrences (see constipation).

Solitary rectal ulcer

These ulcers occur in young adults and produce bowel irregularity and rectal bleeding with the passage of mucus. The cause is unclear, but many seem to be due to excess straining at stool with prolapse of the rectal mucosa (descending perineal syndrome).
Rectal examination is usually normal but sigmoidoscopy reveals redness or an ulcer approximately 10 cm from the anal margin on the anterior rectal wall. It often has an appearance not unlike that of a carcinoma. Histology is diagnostic; there are non-specific inflam matory changes with bands of smooth muscle extending into the lamina propria. Treatment is unsatisfactory and many cases run an indolent chronic course with continuation of symptoms. Local steroids may help and surgical excision should be avoided. Patients should be advised to stop straining on defecation.

Rectal prolapse

In this common condition affecting children and the elderly the rectal mucosa prolapses through the anus owing to excessive straining. Initially prolapse occurs only during defecation but later ulceration, mucosal discharge and faecal incontinence can occur. Surgical treatment is required in complete prolapse.

COLONIC TUMOURS

Colon polyps and polyposis syndromes 

A polyp is an elevation above the mucosal surface. The majority of colorectal polyps are adenomas with malignant potential. Polyps range in size from a few millimetres to 10 cm in diameter. They may be single or multiple and in the polyposis syndromes hundreds may be found. Not all colorectal polyps are adenomas.
In adults, 2-5 mm polyps in the rectum are often found: 90% of these will be of the innocent metaplastic type. Larger polyps in the rectum and 70-80% of all polyps in the colon are adenomas and 5% (20% of those 2 cm or greater in diameter) will contain invasive carcinoma at discovery. Most polyps are asymptomatic and found by chance when patients are investigated for pain, altered bowel habit, bleeding haemorrhoids or some other cause.
HAMARTOMATOUS POLYPS are commonly large and stalked and are either juvenile or Peutz-Jegher in type.

JUVENILE POLYPS (occurring in children and teenagers) are confined mainly to the colon and histologically show mucus-retention cysts. They are inherited as an autosomal dominant and are a cause of bleeding and intussusception, often in the first year of life. In juvenile polyposis (more than 10 colonic polyps) there is an increased risk of colonic cancer and surveillance and removal of polyps must be undertaken.
PEUTZ-JEGHER POLYPS are usually multiple and histologically have characteristic fibromuscular fronds radiating between disorganized mucosal crypts. They can occur in the large intestine, producing chronic anaemia.
Other non-neoplastic polyps are less common and are shown. In the Cronkhite-Canada syndrome, polyps similar to Peutz-Iegher, are associated with ectodermal abnormalities such as alopecia, nail dystrophy and skin hyperpigmentation.

NEOPLASTIC POLYPS Adenomas occur in about 10% of the population in the Western World but are rare elsewhere in the world. Genetic and environmental factors have been implicated but no definite aetiological factors have been identified.
Polyps rarely produce symptoms and most are diagnosed on X-ray or on colonoscopy performed for other reasons. Large polyps may bleed intermittently and cause anaemia. Large sessile villous adenomas of the rectum can present with profuse diarrhoea and hypokalaemia. The frequency with which invasive carcinoma occurs in adenomas increases with the size of the polyp and most, if not all, colonic carcinomas originate as adenomas. Once a polyp has been found on X-ray or endoscopy it is usually removed endoscopically. Further polyps may develop (30-50% probability) and continuous surveillance in patients under 75 years of age is necessary. An initial colonoscopy examination is made at 3 years, followed by 3-5 yearly colonoscopies thereafter.

FAMILIAL ADENOMATOUS POLYPOSIS (FAP) is inherited as an autosomal dominant trait. Linkage studies in families have shown that the gene involved (ape) is on the long arm of chromosome 5. In FAP, multiple polyps are found throughout the gastrointestinl tract, the colon and duodenum being particularly involved. Constant endoscopic surveillance is necessary as all patients with FAP eventually develop cancer if followed long enough. An attempt should be made to remove all colonic polyps, but this is often impossible and, therefore, in this high-risk group and in any relative found to have polyps (relatives must be screened after 12 years of age) a colectomy with an ileorectal anastomosis is performed with long-term surveillance of the rectal stump. A new test using lymphocytes isolated from peripheral blood that can identify APC mutations in approximately 7% of patients may become generally available. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) can be seen in two-thirds of FAP patients and is useful for screening in young patients. Gardner’s syndrome is a variant of this condition in which, in addition to adenomatosis, there are mesodermal tumours (e.g. dermoid tumours, osteomas of the skull) and pigmented ocular fundal lesions.

Acute attacks are treated with bowel rest, intravenous fluids and antibiotics, e.g. gentamicin (or a cephalosporin) and metronidazole. Most attacks settle on this regimen, but a few require emergency surgery, which usually consists of a defunctioning colostomy to be followed later by resection.
Acute episodes do not necessarily recur and elective surgery is mainly reserved for patients with intestinal obstruction or fistulae.

CONSTIPATION

This is such a major problem in the general population that it need not be considered a disease. Most people simply require reassurance and dietary advice. Constipation is common in the elderly, possibly due to immobility and a poor diet. Constipation in young women is common and in some slow transit through the colon has been identified as the cause, whilst some women after childbirth have pelvic floor abnormalities preventing defecation. A list of the causes of constipation is given. Most have simple constipation, often due to a low fibre intake. Drugs are a common cause and may need to be stopped. A rectal examination should always be performed. Long-standing constipation does not require investigation, but a change in bowel habit in the middle-aged or elderly requires a barium enema examination.

TREATMENT

Laxatives should be avoided if at all possible and patients encouraged to take a high-fibre diet. Glycerol suppositories,
which can be used by the patient, are often useful. The types of laxatives available are shown . Bulking agents should be tried first. Stimulant laxatives often cause cramp and their long-term use should be avoided as they cause an atonic non-functioning colon. Magnesium sulphate is useful in very severe constipation.

Megacolon

The term megacolon is used to describe a number of congenital and acquired conditions in which the colon is dilated. In many instances it is secondary to chronic constipation and in some parts of the world Chagas’ disease is a common cause.
All young patients with megacolon should have Hirschsprung’s disease excluded. In this disease, which presents in the first years of life, an aganglionic segment of the rectum gives rise to constipation and subacute obstruction. Occasionally Hirschsprung’s disease affecting only a short segment of the rectum can be missed in childhood and a rectal biopsy, using special stains for ganglion cells in the submucosal plexus, should be performed in adult patients with megacolon to exclude it; frozen rectal mucosa should be stained for acetylcholinesterase. Pressure studies show failure of relaxation of the internal sphincter, which is diagnostic of Hirschsprung’s disease. This disease can be successfully treated surgically. Treatment of megacolon is similar to simple constipation,
but saline wash-outs and manual removal of faeces are sometimes required.

Pneumatosis cystoides intestinalis

This is a rare condition in which multiple gas-filled cysts are found in the submucosa of the intestine, chiefly the colon. The cause is unknown, but many cases are associated with chronic bronchitis and some with peptic ulceration. Patients are usually asymptomatic but abdominal pain and diarrhoea do occur and occasionally the cysts rupture to produce a pneumoperitoneum. This condition is diagnosed on X-ray of the abdomen, barium enema or at sigmoidoscopy when cysts are seen. Treatment is often unnecessary but continuous oxygen therapy will help to disperse the largely nitrogen-containing cysts. Metronidazole may help.

Ischaemic disease of the colon (ischaemic colitis)

This commonly presents in the older age group (over 50 years) with sudden onset of abdominal pain and the passage of bright red blood with or without diarrhoea. There may be signs of shock and there is sometimes evidence of other cardiovascular disease. This condition has also been described in young women taking the contraceptive pill. On examination, the abdomen is distended and tender. Sigmoidoscopy is normal apart from the presence of blood. Investigations include an abdominal X-ray to exclude perforation. Thumbprinting-a characteristic sign for ischaemic disease-can be seen on a barium enema performed when the patient is well; strictures can also be seen.
The differential diagnosis is of other causes of acute colitis, but these can usually be excluded on the basis of the sigmoidoscopy findings.

TREATMENT

Most patients with this condition settle on symptomatic treatment. A few develop gangrene and perforation andrequire urgent surgery. Some develop strictures.

STRUCTURE

The large intestine starts at the caecum, on the posterior medial wall of which is the appendix. The colon is made up of ascending, transverse, descending and sigmoid parts, which join the rectum at the rectosigmoid junction. The muscle wall consists of an inner circular layer and an outer longitudinal layer. The outer layer is incomplete, coming together to form the taenia coli, which produce the haustral pattern seen in the normal colon. The mucosa of the colon is lined with epithelial cells with crypts but no villi, so that the surface is flat. The mucosa is full of goblet cells. A variety of cells, mainly lymphocytes and macrophages, are found in the lamina propria. The blood supply to the colon is from the superior and inferior mesenteric vessels. Generally there are good anastomotic channels, but the caecum and splenic flexure are areas where ischaemia can occur.
The rectum is about 12 cm long. Its interior is divided by three crescentic circular muscles producing shelf-like folds. These are the rectal valves and can be seen at sigmoidoscopy. The anal canal has an internal and an external sphincter.

PHYSIOLOGY

The main role of the colon is the absorption of water and electrolytes (Table 4.11). Approximately 2 litres of fluid passes the ileocaecal valve each day. The absorption of fluid and electrolytes takes place mainly in the right side of the colon, and only about 150 rnl is passed in the faeces. The role of the rectum and anus in defecation is complex. The rectum is usually empty and collapsed; the entry of faeces from the colon produces relaxation of the internal sphincter and the puborectalis muscle. This decreases the acute angle between the rectum and the anal canal. When the rectum contains approximately 100 ml of faeces the urge to defecate is experienced. The rectum is emptied by relaxation of the external anal sphincter (under voluntary control) and an increase in intraabdominal pressure.

Diverticular disease

Diverticula are frequently found in the colon and occur in 50% of patients over the age of 50 years. They are most frequent in the sigmoid, but can be present over the whole colon.
The term diverticulosis’ indicates the presence of diverticula; diverticulitis implies that these diverticula are inflamed. It is perhaps better to use the more general term diverticular disease, as it is often difficult to be sure whether the diverticula are inflamed. The precise mechanism of diverticula formation is not known. There is thickening of the muscle layer and, because of high intraluminal pressures, pouches of mucosa extrude through the muscular wall through weakened areas near blood vessels to form diverticula. Diverticular disease seems to be related to the low-fibre diet eaten in the western hemisphere.

Diverticulitis occurs when faeces obstruct the neck of the diverticulum causing stagnation and allowing bacteriato multiply  and produce inflammation. This can then lead to bowel perforation (peridiverticulitis), abscess formation, fistulas into adjacent organs, or even generalized peritonitis.

CLINICAL FEATURES AND MANAGEMENT

Diverticular disease is asymptomatic in 90% and is usually discovered incidentally on a barium enema examination; no treatment is required. Left iliac fossa pain, constipation and diarrhoea are often attributed to diverticular disease, but as these symptoms are very similar to those seen in the irritable bowel syndrome, it is debatable whether they are due to diverticular disease. In practice, both conditions are treated symptomatically with a high-fibre diet, antispasmodic drugs (e.g. mebeverine 135 mg three times daily) and agents to regulate the bowel. A barium enema is often performed to exclude colonic carcinoma. Diverticular disease can produce rectal bleeding, which is sometimes massive, particularly from right-sided diverticula. In most cases the bleeding stops and the cause of the bleeding can be established by X-ray, colonoscopy and sometimes angiography. In rare cases emergency colectomy is necessary. It is unwise to ascribe an iron deficiency anaemia to a bleeding diverticulum unless all other causes, e.g. piles or carcinoma, have been excluded.

ACUTE DIVERTICULITIS almost always affects diverticula in the sigmoid colon. It presents with severe pain in the left iliac fossa, often accompanied by fever and constipation. These symptoms and signs are similar to appendicitis but on the left side. On examination there is tenderness, guarding and rigidity on the left side of the abdomen. Tachycardia and pyrexia are present and the white cell count shows a leucocytosis. Chest and abdominal X-rays are necessary to exclude free air under the diaphragm and an ultrasound is performed to detect an abscess following localized perforation.

Complications of acute diverticulitis

ABSCESS FORMATION, causing pain, pyrexia and a palpable tender mass in the left iliac fossa. Ultrasound or CT scanning can show the mass. Surgical drainage with or without a defunctioning colostomy may be required. Antibiotics are always given.

PERFORATION, leading to generalized peritonitis.
FISTULA FORMATION into the bladder, causing dysuria or pneumaturia, or into the vagina, causing discharge; the diverticular disease is often chronic, without evidence of acute inflammation. Surgery is usually required.

Blood tests

Anaemia is common and is usually the normocytic, normochromic anaemia of chronic disease. Deficiency of iron and/or folate also occurs. Despite terminal ileal involvement in Crohn’s disease, megaloblastic anaemia due to vitamin B\2 deficiency is unusual, although the vitamin B’2 level can be low. There is often a raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and a raised white cell count. Hypoalbuminaemia is present in severe disease. Liver biochemistry may be abnormal. Blood cultures are required if septicaemia is suspected.

Stool cultures

These should always be performed on presentation if diarrhoea is present.

Radiology

CROHN’S DISEASE. A small bowel follow-through is usually performed first unless the disease is predominantly Crohn’s colitis.
A small bowel follow-through shows an asymmetrical alteration in the mucosal pattern with deep ulceration and areas of narrowing (string sign) largely confined to the ileum. Skip lesions with normal bowel between are also seen.
Barium enema has been superseded by colonoscopy, if this is available, for colonic disease. Early changes on barium enema consist of aphthous ulceration; this involvement is again usually patchy with deep ulceration developing later.
Ultrasound and CT scanning are helpful in delineating abscesses, masses, thickened bowel wall and mesentery, or other extraluminal problems in Crohn’s disease.
ULCERATIVE COLITIS. A plain X-ray of the abdomen is performed in severe colitis cases to look for colonic dilatation. The extent of the disease can be judged by the air distribution in the colon.

In an instant, unprepared barium enema, barium is run into the rectum without pressure and a single film taken. This is a good investigation to show the extent of the disease. Barium enema is again being superseded by colonoscopy. If performed, there may be ulceration and in longstanding disease the colon is shortened and narrowed . The disease is usually continuous.

Colonoscopy

In Crohn’s disease, this is performed if colonic involvement is suspected when biopsies of the whole colon can be taken. In ulcerative colitis, colonoscopy shows the exactextent of the disease and, again, biopsies from the whole colon and ileum can be taken to differentiate between Crohn’s disease and ulcerative colitis.

Small bowel function tests

When Crohn’s disease involves the small bowel, other tests may be necessary, e.g. a breath test for bacterial overgrowth or a test for vitamin Bl2 absorption.

ACTIVITY OF DISEASE

A rough estimate of the activity can be made on the clinical picture and laboratory tests of ESR, serum albumin and acute-phase protein (e.g. CRP or orosomucoids). In some centres scans to localize areas of inflammation are performed using radiolabelled leucocytes injected intravenously; these may help in localizing abscesses.