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We reviewed a set of cases of early neoplasia (low grade / high grade dysplasia / IEN and mucosal carcinoma) to reach better defined criteria for subtypes of dysplasia/differentiation in the columnar lined (Barretts) esophagus. We discuss criteria that we categorized for recognizing low and high-grade dysplasia and mucosal carcinoma in patterns of neoplasia that we regarded as intestinal, gastric and mixed.

This chapter deals with pre-malignant epithelial lesions of the gastrointestinal tract that have the potential to become cancers. Pre-malignant lesions are divided into two types: those characterized by dysplastic mucosa and those without dysplasia. Examples of the two types are present in the oesophagus, stomach and intestine. In the oesophagus, dysplasia of the squamous epithelium is a precursor to squamous carcinoma. There are differences in interpretation between Western and Japanese pathologists in the diagnosis of oesophageal squamous lesions. Dysplasia in Barrett's oesophagus is regarded as a precursor of adenocarcinoma. The goal of endoscopic surveillance in Barrett's mucosa is the detection of high-grade dysplasia. There are several problems with our current knowledge of high-grade dysplasia and controversies regarding its management. There are differences in the interpretation of biopsies of gastric epithelial dysplasia between Japanese and Western pathologists. In the colon, pre-malignant lesions include dysplasia seen in inflammatory bowel disease and colonic adenomas. The most significant predictor of the risk of malignancy in patients with inflammatory bowel disease is the presence of dysplasia in colonic biopsies. Because of the similarity of neoplasia throughout the gastrointestinal tract, there have been attempts to unify its classification, terminology and diagnostic criteria internationally, the most recently proposed modified classification of gastrointestinal neoplasia being the Vienna classification. Dysplasia of the columnar mucosa has a similar appearance in Barrett's oesophagus, the stomach and the colon. Criteria for its histological diagnosis and grading are reviewed, with an emphasis on areas of diagnostic difficulty such as interobserver variation, and discrepancies between Western and Japanese pathologists. Implication of the presence of dysplasia that are specific to each organ site are discussed, highlighting weaknesses and controversies in current knowledge., (Copyright 2001 Harcourt Publishers Ltd.)

Background: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions., Aim: To develop common worldwide terminology for gastrointestinal epithelial neoplasia., Methods: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology., Results: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond)., Conclusion: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

It has become increasingly apparent that the Japanese and Western systems of classifying dysplasia and carcinoma in the gastrointestinal tract are not the same. The implication of these differences is that in an article in a Western journal on gastrointestinal 'cancer' originating from Japan, it is often impossible to repeat the study to confirm or refute it because of these differences in definitions. 'Carcinoma' is diagnosed in Japan by virtue of its structural and cytological features but by invasion in the Western system. Adenoma does not mean a dysplastic lump in the Japanese system (although it can), but in most cases is similar to low grade dysplasia irrespective of the macroscopic and/or endoscopic appearances (hence flat and depressed adenomas in the Japanese system); however, most examples of high grade dysplasia in the Western system, as well as some low grade dysplasia, are 'cancer' in the Japanese system. Conversely, both have conceptual areas that are useful in the other's system.

Background: In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries., Methods: Eight expert pathologists from Japan (4), North America (2), and Europe (2) individually reviewed microscope slides of 20 colorectal lesions from Japanese patients who had undergone endoscopic mucosal resection or surgery because early stage carcinoma and/or adenoma was suspected. The pathologists indicated the pathologic findings on which they based each diagnosis., Results: For 11 slides that showed adenoma according to the Western pathologists with low grade dysplasia according to at least half of them, the Japanese diagnosed definite carcinoma with or without adenoma in 4 cases and adenoma in 5, and in 2 cases they were equally divided between a diagnosis of adenoma and carcinoma. For five slides showing adenoma with high grade dysplasia according to the Western pathologists, the Japanese diagnosed definite carcinoma with adenoma in three cases and adenoma in one, and in one case they were equally divided between a diagnosis of adenoma and carcinoma. For one case in which the Western pathologists were equally divided between a diagnosis of carcinoma and adenoma with high grade dysplasia, all the Japanese pathologists diagnosed definite carcinoma with or without adenoma. Three slides showed definite carcinoma with or without adenoma, according to both the Western and the Japanese pathologists. The presence of invasion was the most important diagnostic criterion of colorectal carcinoma for the Western pathologists, whereas for the Japanese the nuclear features and glandular structures were more important., Conclusions: In Japan, colorectal carcinoma is diagnosed on the basis of nuclear and structural criteria, even in cases considered by Western pathologists to be noninvasive lesions with low grade dysplasia. This diagnostic practice may contribute to the relatively high incidence of early stage colorectal carcinoma reported in Japan as compared with Western countries.

Background: There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan., Methods: Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis., Findings: For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important., Interpretation: In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries.

Now that many of the problems associated with the recognition, classification and terminology of dysplasia in ulcerative colitis have been overcome, the clinical effectiveness of such a classification needs to be investigated. Because dysplasia has been defined as an unequivocally neoplastic transformation of the epithelium which is capable of giving rise to an invasive carcinoma, it follows that in waiting for the development of dysplasia in patients at risk, there will always be an associated and as yet undefined incidence of invasive carcinoma already being present. Nevertheless, it is currently inappropriate to consider proctocolectomy before such changes develop. It is emphasised that waiting for high grade dysplasia to develop may lead to an unacceptably high level of associated invasive carcinoma. Also, because dysplasia is frequently focal, the changes of detecting it on random biopsy are directly proportional to the number of biopsies taken, and if found in flat mucosa it may be difficult to confirm the presence of such dysplasia by re-biopsy. Colectomy at this stage is aimed at cancer prevention rather than early cancer detection. Conversely, targeted biopsies of endoscopically visible plaques, nodules or other abnormalities, which may already be the superficial part of invasive carcinomas, offer the best hope of early detection of carcinoma. However, a proportion of these may have metastasised already; this is much more likely to have occurred if such a lesion is found at the first colonoscopy rather than in a patient in whom several surveillance colonoscopies have been carried out. Finally, the initial stages of many colitic cancers are undetectable endoscopically or radiologically but may be biopsied accidentally. All of these factors suggest that unexpected carcinomas will occur in any long-term prospective study. Surprisingly, most will not be lethal and they can be kept to a minimum if proctocolectomy is considered once unequivocal dysplasia is demonstrated on biopsy, particularly in parts of the world where large bowel cancer is already common. Data are required which assess accurately the risk of an invasive carcinoma being present or developing when epithelium indefinite for dysplasia, low grade dysplasia or high grade dysplasia are present both with and without an endoscopic abnormality being the source of the biopsy, and when such biopsies are obtained at the first or at subsequent colonoscopies. Only then can the risks of colectomy be weighed adequately against the likelihood of carcinoma already being present.(ABSTRACT TRUNCATED AT 400 WORDS)

Fifty-one patients with metastatic colorectal carcinoma confined to the liver received intraarterial chemotherapy through the hepatic artery via a subcutaneous pump. The chemotherapy consisted of sequential 14-day infusions of floxuridine (FUDR) and dichloromethotrexate (DCMTX) or a 14-day infusion of FUDR and bolus mitomycin (MMC). Twenty-four patients (47%) developed hepatitis with an elevation of hepatic serum transaminase (serum glutamic oxaloacetic transaminase, SGOT, or serum glutamic-pyruvic transaminase, SGPT). The median time to develop hepatitis was 11 weeks after initiation of chemotherapy. The morphologic effects of chemotherapy were evaluated in eight patients with hepatitis. All the patients with hepatitis had normalization of the serum transaminases after temporary cessation of chemotherapy. There was a trend toward a greater chance of remission in patients who developed hepatitis. Sixty-seven percent of the patients with a therapeutic response had hepatitis, whereas only 33% of the patients without a response had hepatitis. However, this difference was not statistically significant. The occurrence of hepatitis was not related to FUDR dose, drug program (FUDR-DCMTX vs. FUDR-MMC), pump flow rate, hepatic arterial anatomy, sex, or age of the patients.

Six patients with Crohn's disease and intestinal carcinoma are presented who demonstrated dysplastic changes in their intestinal mucosa. These changes were present adjacent to and/or distant from the infiltrating carcinoma and were extensive in 2 of these patients. The dysplasia affected many different cell types and was in many ways similar to that seen in ulcerative colitis. In view of the difficulties in making a clinical diagnosis of carcinoma in Crohn's disease, the finding of these changes on biopsy should be a strong indication for resection. However, as many of the carcinomas in Crohn's disease occur in excluded loops and in the small intestine, these changes will be of less value clinically than in ulcerative colitis, because access to these areas is difficult.

A young man presenting with Cushing's syndrome was found to have multiple endocrine neoplasia type 2b MEN 2b and adenomatous colonic polyposis with duodenal and gastric polyps. The entire syndrome of MEN 2b was present, including metastatic medullary carcinoma of the thyroid, a pheochromocytoma, and peripheral nerve abnormalities. The concurrence of these two inherited multiple neoplasia syndromes may reflect a common pathogenetic step in this patient.