Seminars in gastrointestinal disease最新文献

Flat adenomas have a higher risk of association with adenocarcinoma than the protruded type, and flat cancer has a tendency to invade deeply despite its small size. Furthermore, it has been suggested that flat, small carcinomas readily invade through the muscularis mucosa into the submucosa and are associated with an increased risk of early metastasis into lymph nodes, as compared with polypoid growth pattern cancers. It has become evident that these lesions are becoming more common in Japan, as well as in some western countries. It has been generally believed that the colon is comparable to the stomach in terms of endoscopic diagnostic capability and accuracy. Therefore, we were surprised to learn that flat neoplasms, including flat or depressed adenomas and cancers, exist in the colon, as they seem to have previously been overlooked. Recent significant advances in endoscopic resolution and the development of improved diagnostic techniques and modalities may play an important role in the detection of such lesions. In the present study, the diagnosis and management of such lesions, along with their genetic background, is reviewed. Some techniques for their detection currently being used in Japan will also be reviewed using several actual cases.

Screening for colorectal cancer is only beginning to receive the attention it deserves. As screening emerges into the mainstream and utilization increases, competing technologies will battle to assume a greater percentage of the market share of testing. In this review, the standards and principles with which screening tests are evaluated are outlined. Current modalities for screening, including fecal occult blood testing (FOBT), flexible sigmoidoscopy, colonoscopy, barium enema, and the combination of FOBT with sigmoidoscopy, are discussed and critically reviewed. New techniques and technologies for screening, including virtual colonoscopy and molecular methods of screening stool, are previewed. Increased attention on screening and the competition for supremacy among the modalities undergoing evaluation make the prospects for a continued diminution in colorectal cancer mortality promising.

The adenoma-carcinoma sequence postulates that colorectal carcinomas arise from precursor lesions, called adenomas. All adenomas contain dysplastic epithelium that arises from mutations in either the adenomatous polyposis coli gene or DNA mismatch repair genes. The earliest lesion detected with dysplasia is the aberrant crypt focus. Over time, as this lesion acquires additional mutations, it evolves into a classic adenomatous polyp. Adenomatous polyps are classified as tubular, tubulovillous, or villous. Generally, as polyps increase in size, the degree of dysplasia worsens, the villous component increases, the number of genetic abnormalities increases, and the likelihood of harboring invasive carcinoma increases. Carcinomas associated with DNA mismatch repair mutations are more likely to be poorly differentiated and incite a host lymphocytic response. These tumors seem to have a better prognosis, stage for stage, than typical colorectal carcinomas.

Our understanding of the biology of colon cancer has matured to the point that it is a useful general paradigm for understanding solid tumor development. Recent advances provide insight into the genetic alterations underlying the development of colon cancer. These insights provide unique opportunities for genetic testing in predisposed, asymptomatic patients that can direct screening efforts and their clinical management. This review examines several inherited colon cancer predispositions, well described clinically for a century, that are now amenable to genetic testing. Additional discussion focuses on colon cancer predisposition traits that occur with high frequency but low penetrance characteristics. Finally, genetic tests for tumor markers that potentially have prognostic or therapeutic implications are reviewed.

The genes responsible for each of the inherited syndromes of intestinal polyposis and colorectal cancer are now known. This knowledge has led to genetic testing for syndrome diagnosis and for determining which persons in an affected family actually have the condition. Genetic testing has also allowed a more precise clinical characterization of each of the syndromes and their subtypes. Optimal application of genetic testing, proper cancer prevention, and management of nonmalignant features of each of the syndromes are the next goals. This report summarizes each of the syndromes, their genetics, and management and provides an approach for genetic testing.

Bile duct and gallbladder cancer are relatively uncommon. Predisposing factors include primary sclerosing cholangitis and gallstones larger than 3 centimeters. Patients present with signs of biliary obstruction and cholestasis. A serum CA 19-9 elevated above 100 U/mL is a useful marker. The diagnosis is implied on imaging studies and confirmed by tissue obtained at endoscopic retrograde cholangiopancreatography or surgery, or by the clinical course. Surgery is the only curative therapy and survival is improved with resection of early stage disease. Endoscopic or percutaneous transhepatic stenting provides effective palliation. Generally, survival is less than 1 year.

Diet and lifestyle modification offers means of reducing risk of developing colon cancer. Current data suggest that consuming a Western style diet, that is, one high in meat, refined grains, and sugar and low in vegetables and fiber, may contribute to risk of colon cancer. There also are data to support a reduction in colon cancer risk from consuming high levels of calcium and folate. Energy balance and maintaining an appropriate body weight have been associated with a reduced risk of colon cancer. An important part of the energy balance equation is physical activity. High levels of physical activity have consistently been identified as being associated with a reduced risk of colon cancer. It is estimated that 13% of colon cancer can be attributed to being physically inactive, 12% of colon cancer can be attributed to eating a Western style diet, and 8% of colon cancer can be attributed to having a first degree relative with colorectal cancer.

Adjuvant therapy is widely recommended for stage III colon cancer and stages II and III rectal cancer. Although fluorouracil-based regimens are standard, newer agents either alone or in combination may improve response rates. Although nearly all patients enter a postoperative surveillance program after surgical resection, the clinical effectiveness of such surveillance, which is not standardized, is questionable. Critical review of the use of different components (laboratory, radiographic, and endoscopic) of these programs finds little support for intensive surveillance.

The discovery of Helicobacter pylori and its relationship to upper gastrointestinal tract diseases has emphasized the significance of infectious pathogens in clinical disease. Severe manifestations of H. pylori-associated diseases include gastric adenocarcinoma and the recently described gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Ongoing worldwide investigations of the interactions of H. pylori and the host response are rapidly clarifying the role of this bacterium in multiple gastrointestinal diseases. This review will address diagnosis, management, and follow-up of the patient presenting with gastric MALT lymphoma, including a discussion of the issues related to premalignant lesions associated with gastric adenocarcinoma. Prospective trials and long-term follow-up studies are in progress and will guide appropriate management of these diseases.

Carcinoid tumors most commonly occur in the gastrointestinal tract and are known best for the bizarre manifestations of the carcinoid syndrome caused by the release of tumor products. However, many carcinoid tumors do not present with or cause the carcinoid syndrome, and this has led to the development of new diagnostic markers for these tumors. New treatments have emerged recently and are being developed, because although these tumors are relatively indolent, they can metastasize. The biology of carcinoid tumors of the gastrointestinal tract can be classified in large part by the embryologic regions of the gut in which they occur. More carcinoid tumors will be discovered as the indications and use of gastrointestinal endoscopies increase, so the diagnosis and initial management of carcinoid tumors will fall largely on the gastroenterologist.