The best prospect of realizing a reduction in mortality from colorectal cancer appears to be by presymptomatic detection in a screened population. Presently, the only feasible method of mass population screening is by the detection of faecal occult blood and it is encouraging that all the major trials demonstrate that asymptomatic malignancy may be detected in this way. Furthermore, the screen-detected cancers are generally at an earlier pathological stage than those appearing in control populations. However, a note of caution is required. At the present time it is too early to demonstrate a reduction in mortality from the disease and there is evidence of a length bias, with more of the screen-detected cancers being well differentiated. The results of the large controlled trials will enable the benefits of screening to be viewed objectively and a recommendation for, or against, screening to be made.

It is possible to make a histopathological diagnosis of colorectal carcinoma from ulcerating lesions by means of forceps biopsy, but this presents problems in polypoid tumours. In order to make the diagnosis of invasive carcinoma, evidence of invasive growth into the submucosa is necessary. In polypoid tumours, this can be done usually only by endoscopic or surgical polypectomy. In addition to histopathological diagnosis, one of the most important tasks for the contemporary pathologist is the exact classification of colorectal tumours. The most important parameters are typing, grading, staging and the R classification, i.e. the assessment of presence or absence of residual tumour following treatment. Typing and grading is done according to the WHO recommendations; the great majority of colorectal carcinomas are adenocarcinomas or mucinous adenocarcinomas. In grading, one can differentiate into either four grades (G1 to 4) or between low and high grade. The internationally accepted TNM/pTNM system, as described in the 4th edition, is used for staging. This system has considerable advantages over the traditional, but often misused Dukes' classification. After treatment, the surgeons and the pathologists must work together to determine the R classification. Typing, grading and staging are of great importance in deciding on the indication for either a limited surgical procedure or a radical resection. Together with the R classification, they decisively influence the indications for post-treatment after surgical therapy. R classification is the most important factor for prognosis after surgical removal of tumours. Following resection for cure, the prognosis is especially affected by the pTNM classification and its corresponding stages. The independent prognostic significance of other clinical, macroscopic and histological findings cannot yet be definitively determined.

The nature of gastric infiltrates consisting primarily of benign-appearing small lymphocytes is at present a controversial issue. Earlier reports of gastric lymphoma developing in gastric pseudolymphoma and more recent immunohistochemical studies demonstrating monoclonal B-cell populations in pseudolymphoma suggest that at least some cases represent low-grade lymphomas or clonal precursor lesions that may develop into lymphoma. Observations of a small lymphocytic infiltrate arising in the region of a gastric ulcer that lacked definitive morphologic evidence of malignancy (lymphoma) but was clearly a monoclonal B-cell proliferation by immunohistochemical and gene rearrangement studies support the notion that some gastric lymphoproliferative lesions that histologically have been called pseudolymphomas may include one or more clonal lymphoid expansions. A histopathologic/molecular model suggesting a potential pathway for the development of morphologically recognizable lymphoma from benign-appearing small lymphocytic infiltrates is presented, and the concept that for a variety of lymphoid proliferations clonality and malignancy may not be synonymous is discussed.

Familial adenomatous polyposis (FAP) affects around 1 in 10,000 individuals; the gene for this condition was recently shown to be located on chromosome 5, and it is only a matter of time before its precise location and function are determined, making prephenotypic, and even prenatal, diagnosis more generally available and reliable. In the mean time, care of FAP families will continue to depend on careful registration of family information, prophylactic bowel surgery and surveillance for other potentially serious manifestations of the disease. Upper gastrointestinal malignancies and desmoid tumours have overtaken colorectal cancer as the leading causes of death in some centres. Other dominantly-inherited colorectal cancer syndromes produce less striking phenotypes, but affect far more individuals than FAP. It appears that there are two patterns of hereditary non-polyposis colorectal cancer (HNPCC) syndromes, one involving cases of bowel cancer alone, the other associated with breast and gynaecological cancers; these may prove to be variable expressions of a common gene abnormality. More effort is required by clinicians managing cases of colorectal cancer to identify affected families in order to offer surveillance and appropriate treatment in the hope that such measures may prevent cancer in family members.

The occurrence of hepatobiliary disease with or without jaundice during pregnancy provides both the hepatologist and obstetrician with an interesting and urgent diagnostic challenge. Advances in our understanding and management of liver disorders unique to pregnancy and hepatobiliary disease in general have resulted in a significant improvement in the outcome for both mother and fetus. Certain disorders such as acute fatty liver of pregnancy and hepatic haemorrhage associated with toxaemia should be considered medical emergencies and delay in diagnosis of these conditions will probably adversely affect maternal and fetal outcome. A careful clinical history, physical examination, appropriate laboratory tests and radiological investigations should allow a diagnosis within 24-48 hours of presentation. Liver biopsy is rarely required. A careful history may provide important information. Does the patient have pre-existent liver disease? Has there been contact with hepatitis, intravenous drug abuse or any other factor predisposing to acute viral hepatitis? Does the patient have a family history of pruritus and/or jaundice to suggest intrahepatic cholestasis of pregnancy? Is the patient's alcohol consumption excessive? Has the patient received any hepatotoxic medications? Has there been abdominal pain and/or fever to suggest gallstones, hepatic bleeding or acute fatty liver of pregnancy? Laboratory investigations may give valuable diagnostic clues. Marked aminotransferase elevation would suggest acute viral or 'ischaemic' hepatitis. Haematological features of microangiopathic haemolysis would point towards toxaemia or AFLP. Hepatitis A and B serological tests may be helpful in viral liver disease. Radiological investigations may be indicated depending on the clinical context. Abdominal ultrasonography may be useful in the diagnosis of gallstones, biliary obstruction, liver tumours or intrahepatic bleeding. Fatty infiltration of the liver may be diagnosed by ultrasonography but computed tomography (CT) of the abdomen is probably more reliable for a diagnosis of acute fatty liver of pregnancy as it allows measurement of liver density which is typically reduced by fatty infiltration. CT scanning is also probably more valuable than ultrasound in assessing the extent of capsular rupture and haemorrhage into the liver and peritoneal cavity.

A large number of drugs may be associated with impaired bile flow. Drug-associated cholestasis presents like other forms of cholestasis with pale stools, dark urine, pruritus and jaundice. Abdominal pain may be present in some instances and can be so severe as to lead to a false diagnosis of acute cholecystitis. Biochemically, drug-associated cholestasis resembles other forms of cholestasis although the presence of eosinophilia may suggest drug involvement. Many types of drug-induced cholestasis run a benign course with resolution of signs and symptoms within 3 months but occasionally the jaundice can take a year or more to resolve. Progression to cirrhosis is uncommon. Some patients may develop a syndrome resembling primary biliary cirrhosis. The mechanisms of drug-associated cholestasis are uncertain but may arise from alteration of bile formation within the hepatocyte or bile excretion at the level of the canaliculus or the extrahepatic ducts. Histological examination of the liver may be helpful in classifying the types of jaundice but the diagnosis of drug-induced cholestasis is usually one of temporal association and exclusion of other causes.

Cholestatic syndromes present symptomatically with pruritus and biochemically either with elevated levels of serum bile acid as an early manifestation of hepatocellular disease or with elevated levels of serum alkaline phosphatase if the disease originates in the biliary tree. Slow progression to cirrhosis occurs, with recurrent cholangitis and/or pancreatitis as the major problems if the obstruction is in the larger duct system. Maintenance of nutrition and relief of pruritus are important supportive measures. Colchicine and ursodeoxycholic acid administered orally have been proposed as useful therapies for delaying the progression to cirrhosis. Liver transplantation has proven successful in those patients in whom spontaneous remission does not occur.

The development of computer-assisted diagnostic systems for the differential diagnosis of jaundice has been attempted in several studies during the last 25-30 years. All working systems have depended on numerical methods whereas expert systems have not yet become operational. The first step in the construction of a system is the collection of a data base from a series of jaundiced patients of clinical information (indicants) i.e. symptoms, signs, and the results from laboratory tests. The best discriminating indicants are selected and processed into a mathematical rule. The performance of this rule must be tested on an independent test sample of relevant patients. The performance may also be compared to that of clinicians. So far the computerized diagnoses have not been more accurate than those of clinicians. However, computer-assisted diagnostics may form an important first step in clinical decision making regarding the selection of a confirmatory diagnostic test (direct cholangiography, ultrasonography, liver biopsy, etc.) in the evaluation of the jaundiced patient.

Ultrasonography is the most useful technique for screening patients with suspected obstructive jaundice. Additional information may be gained with CT when US fails either because of disturbing gas-filled loops of bowel or because the patient is obese. A more specific diagnosis is usually obtained from the ERCP which can be combined with percutaneous biopsy and drainage of obstructed bile ducts. PTC and PTCD are left for those patients in whom ERCP has failed.

While Gilbert's syndrome is extremely common and benign, its pathogenesis may not be as straightforward as once believed. It has been used as a model to examine aberrations of virtually every step in bilirubin metabolism. The clinical hallmarks are of a hereditary, chronic, mild unconjugated hyperbilirubinaemia. Not infrequently subclinical haemolysis may coexist. Liver histology is normal although some minor ultrastructural abnormalities may be evident. The universal defect appears to be a reduction in hepatic bilirubin-GT activity. However, other associated abnormalities in bilirubin metabolism, which occur less consistently, suggest that this may not be the sole defect in all patients. The syndrome is almost certainly part of a spectrum which includes the Crigler-Najjar syndromes; molecular biology data suggests that there is an absence of one (or even more) GT isoenzymes in these disorders. Whether one or more genes is consistently culpable remains open to speculation. Despite the complicated pathogenesis of Gilbert's syndrome, management remains simply reassurance alone.