Acta Gastro-Enterologica Belgica最新文献

Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower oesophagus. In 1976, Paull et al. described three types of columnar epithelia lining the distal oesophagus: a junctional or cardiac-type epithelium, a gastric fundic-type epithelium and a distinctive type of intestinal metaplasia referred to as specialized columnar epithelium. Even the normal oesophagus can be lined by 2 cm of columnar epithelium. To avoid the problem of false-positive diagnoses, arbitrary criteria for the extent of oesophageal columnar lining necessary to include patients in studies of Barrett's oesophagus were established in the early 1980s. The latter criteria require a circumferential segment of columnar lined epithelium of 2 or 3 cm in length. There are, however, a number of technical and conceptual problems related to this approach. The traditional definition excludes shorter segments and tongues of columnar lined epithelium. Only the specialized columnar epithelium defined by intestinal type goblet cells carries an inherent risk of malignancy. Therefore, a number of investigators currently define Barrett's oesophagus as any amount of columnar mucosa in the lower esophagus that has histologic evidence of goblet cells (highlighted in biopsies using the alcian blue pH 2.5 stain). Recently, short segments of specialized intestinal metaplasia in the distal oesophagus ("short segment Barrett's oesophagus") have attracted considerable attention. It has also become clear that intestinal metaplasia can occur at a normally located gastro-oesophageal junction. The etiology and clinical significance (in terms of possible relationship to the adenocarcinoma of the cardia) of this "intestinal metaplasia of the gastric cardia" and its potential relationship to Barrett's oesophagus are not yet completely understood.

In the gastrointestinal tract, epithelial dysplasia is defined as an "unequivocal neoplastic transformation, confined within the boundaries of the basement membrane" or "the presence of unequivocally neoplastic cells that replace a variable proportion of the normal epithelium". It can be recognized by microscopy because of cytological and architectural changes. Reactive changes or equivocal changes should thus not be called "dysplasia". As dysplasia is confined within the basement membrane, it is a noninvasive neoplastic transformation. In the lower esophagus lined by columnar epithelium (Barrett's esophagus) dysplasia is classified as negative, indefinite or positive. Positive lesions are subdivided into low-grade and high-grade dysplasia according to the severity of the lesions. Carcinoma in situ (intraepithelial carcinoma) is included in the category of high-grade dysplasia. The presence of dysplasia can be recognized on biopsies and on cytological preparations. Several techniques have been introduced with the purpose to improve the diagnostic yield. These include special stains for the assessment of mucin, enzymehistochemistry and immunohistochemistry for tumor markers such as CEA and CA 19-9 and molecular techniques. Mucin histochemistry, enzymehistochemistry and immunohistochemistry for traditional markers have limited practical value. The nuclear presence of abnormal products such as mutant p53 can be identified using immunohistochemistry and appropriate antibodies. Flow cytometry can identify aneuploid cell populations and Fluorescent In Situ Hybridization (FISH) can identify chromosomal gains and losses. These techniques provide additional information but they identify other phenomena which do not necessarily appear at the same moment as dysplasia during the process of carcinogenesis. Application of these techniques can however certainly help to support a diagnosis of dysplasia while negative results do not necessarily disproof such a diagnosis. The temporal course of the progression of dysplasia and the development of carcinoma is not well known and seems to be variable. Low-grade dysplasia may persist for long periods. A direct progression towards carcinoma has been noted although more often an increase in the severity of the dysplasia, before the development of carcinoma, was seen during the observation period. High-grade dysplasia can also persist for many months, sometimes even years without obvious evolution but it can also progress rapidly to carcinoma.

Barrett's esophagus is an acquired condition characterized by a progressive columnar metaplasia of the distal esophagus caused by longstanding gastroesophageal reflux and reflux esophagitis. Barrett's esophagus is a premalignant condition associated with a significantly increased risk of developing esophageal adenocarcinoma. The purpose of this article is to provide an overview of the radiologic aspects of Barrett's esophagus and esophageal adenocarcinoma. Review of the literature shows that some findings on esophagography that are relatively specific for Barrett's esophagus are not sensitive, while others that are sensitive have a low specificity. Specific radiologic features allowing a confident diagnosis of Barrett's esophagus are a high esophageal stricture or ulcer associated with a hiatal hernia and/or gastroesophageal reflux. A reticular mucosal pattern is a relatively specific sign particularly if located adjacent to a stricture and is highly suggestive of Barrett's esophagus. Unfortunately, these findings are only present in a minority of cases. More common but nonspecific findings include gastroesophageal reflux, hiatal hernia, reflux esophagitis and/or peptic stricture in distal esophagus. These findings may also be present in patients with uncomplicated reflux disease. Barrett's esophagus carries a risk of malignant change. Early adenocarcinoma may appear as a plaque-like lesion or with focal irregularity, nodularity, and ulceration of the esophageal wall. Invasive adenocarcinoma may be seen as an infiltrating ulcerated mass. The radiologic diagnosis of Barrett's esophagus is limited by lack of criteria that are both sensitive and specific. The major value of double-contrast esophagography is its ability to classify patients into high risk (high stricture, ulcer or reticular pattern), moderate risk (esophagitis and/or distal peptic strictures), and low-risk (absence of esophagitis or stricture) for Barrett's esophagus determining the relative need for endoscopy and biopsy. Endoscopy and biopsy are generally advocated to make a definitive diagnosis. Endoscopic ultrasound plays a role in the early detection of invasive carcinoma and the staging of proven carcinoma but has no role in the surveillance of Barrett's esophagus.

The purpose of endoscopic surveillance in Barrett's esophagus is to detect dysplasia and to diagnose carcinoma in an early, treatable stage. Prospective trials that study the efficacy of a surveillance program in reducing mortality from esophageal adenocarcinoma are lacking. Retrospective studies have shown a significantly better outcome in patients with esophageal cancer that is detected during a surveillance program. Obviously, surveillance is only indicated for those patients fit enough to undergo esophagectomy if high-grade dysplasia (HGD) or malignancy is detected. There is no consensus upon what to do with HGD: some recommend esophagectomy when HGD is diagnosed, because an important proportion of these patients host an adenocarcinoma; others feel that histological proof of malignancy should be established before esophagectomy is proposed. Dysplasia is not a uniform process, causing sampling problems. Using a strict biopsy protocol is helpful to differentiate HGD from carcinoma, but contradictory results about this type of rigorous biopsy protocol have been published. Most groups propose four biopsy specimens, in a circular fashion, from every 2 cm of the Barrett-epithelium, with additional biopsies from any mucosal abnormality. Patients with long-segment Barrett's esophagus need endoscopic surveillance, even if they underwent antireflux surgery. At this moment there are not enough data to support a systematic surveillance of patients with short-segment's Barrett's esophagus. The following endoscopic strategy can be proposed. No dysplasia: surveillance every 2 years. Low-grade dysplasia: surveillance every year; in these cases it is recommended to repeat four-quadrant biopsies at 1 cm interval if numerous biopsies reveal dysplasia to detect foci of HGD/cancer. High-grade dysplasia: repeat immediately four-quadrant biopsies at 1 cm interval; if HGD is confirmed esophagectomy is advised to a patient with acceptable operative risk. Ablation therapy remains experimental.

The prevalence of Barrett's oesophagus has risen over a short time interval implying environmental in addition to genetic aetiological factors. Bile salt effects from duodenogastro-reflux are assuming increasing importance with deoxycholic and taurodeoxycholic acid being particularly associated with Barrett's oesophagus. The cellular biology changes appear to follow a progression from initial inflammation and oesophagitis to metaplasia and dysplasia through to adenocarcinoma. Mechanisms of restitution include epidermal growth factor mediated increases in epithelial thickness. This results in basal stem cells becoming superficially placed and exposed further to luminal refluxed bile salts. Immature stem cells result which undergo mutation to a metaplastic glandular phenotype with intestinal metaplasia. P53 mutation increasingly occurs in progression to dysplasia and carcinoma and may confer a survival advantage of these cell clones by delaying apoptosis. Cell cycling gene mutations occur with accumulation of cells in G2 phase. Disruption of cellular checkpoint mechanisms in the mitotic process result in loss of heterozygosity and aneuploidy including loss of the Y chromosome. Identical mutations between adjacent areas of dysplasia and adenocarcinoma supports clonal expansion as the mechanism of carcinogenesis. APC tumour suppressor gene mutations are conserved in synchronous carcinomas in Barrett's dysplasia and are associated with beta-catenin accumulation in the nucleus and cellular migration with invasion. Cumulative genetic errors result in abnormal clones with metastatic or angiogenic potential. When a clone with malignant potential occurs adenocarcinoma can result completing the progression from inflammation to metaplasia and dysplasia through to adenocarcinoma.

Accurate prediction of short-term survival rate after liver transplantation is one way of selecting recipients and should improve organ allocation. We observed, during the first ten years of our program a striking decline in postoperative mortality with time, a well known observation in Europe as well as in the United States. In 65 adults with parenchymal cirrhosis having received a liver transplant between 1984 and 1994, we examined the possible influence of various preoperative risk factors on one-month mortality rate which was 13.8% in this series. Univariate analysis led to the identification of five significant risk factors: date of transplantation, low serum sodium, previous history of jaundice, ascites and encephalopathy. In the final multivariate analysis however, the date of transplantation emerged as the sole predictive factor of early mortality rate. Therefore, factors such as pretransplantation state of the patient and poor hepatic reserve are counterbalanced by the improvement of surgical skill and other technical aspects, as well as by better perioperative management which have all contributed to the improved results of liver transplantation with time.

Hepatitis C-related cirrhosis is the major indication for liver transplantation (LT). This disease recurs histologically in nearly all the HCV-infected patients during the first postoperative year. Chronic hepatitis C evolves to cirrhosis in 20% of the cases within 5 years after LT. However, the 5-year survival for a HCV-infected recipient is still comparable to that of a patient grafted for another indication; it will become worse later. High viremia after LT is associated with a more severe liver recurrent disease. The influence of viral genotype remains controversial. The impact of the type of immunosuppression on HCV recurrence is unclear. Steroids, that increase viremia, might have a deleterious effect on the outcome of chronic HCV-disease after LT. Antiviral combined therapy (Interferon + Ribavirin) soon after transplantation, before disease recurrence, is probably the best treatment at the present time; this remains still unproven. Retransplantation for HCV recurrent cirrhosis allows a 60% survival at 1 year.

Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their use is still hampered by some drawbacks including delay before efficacy, 20-35% of non responders, relapse at withdrawal of the drugs, possible bone marrow toxicity and other side effects. During the last few years, these drawbacks have been challenged by important studies showing that a better knowledge of the metabolism of these drugs may help to improve their use.

With current antiulcer therapies to eliminate H. pylori infection, non-steroidal antiinflammatory drug use is the main factor involved in resistant peptic ulcers which must be defined as those ulcers that do not heal after 6 (duodenal ulcers) or 8 (gastric ulcers) weeks of treatment with proton pump inhibitors, despite H. pylori eradication. NSAID use (especially aspirin abuse) in patients with resistant ulcers is often surreptitious. Ulcers tend to complicate with stenosis and bleeding, commonly change site, are multicentric and have poorly defined margins. These patients should never undergo surgery unless they develop uncontrolled complications, since ulcer recurrence is the rule. Analgesic abuse and personality disorders might present in some of these patients. Refractory ulcers with no evidence of NSAID use and no evidence of H. pylori infection are rare but not exceptional. Smoking and genetic background seem important factors in patients with this type of ulcers. Idiopathic basal gastric acid hypersecretion might be important in a few patients, but the Zollinguer-Ellison syndrome must be ruled out.