Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.     

Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation

OBJECTIVE: Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. METHODS: Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. RESULTS: Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. CONCLUSION: ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.     

Reconstitution of squamous epithelium in Barrett's oesophagus with endoscopic argon plasma coagulation: a prospective study

BACKGROUND: Barrett's oesophagus is a premalignant condition. Recent reports have suggested that laser coagulation or photodynamic therapy combined with acid suppression may induce reconstitution of squamous mucosa. However, a high percentage of residual glands remain in cases treated with both techniques. Argon plasma coagulation (APC) appears to be an attractive alternative to other thermoablative techniques. The aim of this study was to investigate the reconstitution of squamous epithelium in Barrett's oesophagus after APC. METHODS: Fifteen patients with histologically proven Barrett's oesophagus were included in a prospective study. After base-line documentation by videotaping and biopsies, Barrett's epithelium was treated by repeated APC at intervals of 4-6 weeks until complete squamous restoration was achieved. All patients were kept under high-dose proton pump inhibitor therapy. RESULTS: In 13 patients complete reconstitution of squamous epithelium was achieved. Buried glands after squamous restoration were detected transiently in only one case after the first session. As side effects seven patients had mild retrosternal discomfort. One patient reported severe retrosternal pain for 1 week. He then refused further APC sessions. Another patient was excluded because of noncompliance. During the follow-up period (6-13 months) recurrence of Barrett's epithelium was observed in one patient. CONCLUSIONS: APC is a suitable technique for achieving squamous restoration in Barrett's oesophagus. The rare occurrence of remaining buried glands may result from the homogeneous coagulation achieved by the ionized argon gas beam.     

Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.     

High grade dysplasia/esophageal adenocarcinoma in short segment Barrett's esophagus

Short segment Barrett's esophagus (SSBE) is a frequent finding in patients having endoscopy, but its clinical significance is not fully understood. With the rising incidence of esophageal adenocarcinoma, a potential role of SSBE has been suggested. Biopsy of such lesions may have to be done when seen on endoscopy.     

Charcoal deposits in the esophageal and gastric mucosa

We report the case of a 75-yr-old woman referred for gastrointestinal endoscopy to investigate severe iron deficiency anemia. Black linear lesions were observed in the distal esophagus and stomach. Biopsies revealed aggregates of coarse black foreign material, which was later identified as charcoal. The patient's previous medical history included an antidepressant overdose 5 yr before the current admission. The patient had a gastric lavage, using a large bore orogastric tube, followed by the administration of activated charcoal. The patient had no other history of charcoal ingestion. We propose that the charcoal became entrapped in mucosal tears caused by the traumatic intubation 5 yr previously, causing the incidental mucosal tattooing seen at endoscopy.     

Evaluation of the protracted stress in the esophageal mucosa of rats

The effect of protracted stress upon the DNA synthesis of the esophageal mucosa of the rat was investigated at various time intervals ranging from one to 56 days. A total of 80 Sprague-Dawley rats were investigated. Lots of 25 rats each were either shock-plunged, subjected to swimming in large basins for two hours or were only transported to the swimming laboratory and used as controls. The remaining 5 rats were non-transported (resting) controls. At the end of the above described procedures, all 80 rats received an intraperitoneal injection of 1 microCi3H-thymidine/gr bodyweight. one hour later the rats were killed. Half of the esophagus was processed for DNA extraction and the other half for autoradiography. When compared to day 0 (resting control rats), the DNA values in experimental animals had increased significantly at day 1, decreased significantly at day 7 in swimming rats and risen once again in both experimental groups at day 14 and more notably at day 28. By 56 days, the values had reached those of day 0. When compared to transported controls at each time interval, both experimental groups had significantly higher DNA values at day 1, significantly lower at day 7 and once again, significantly higher at day 28. Autoradiographic studies of plunged rats showed similar fluctuations in the percentage of labelled basal-parabasal cells in the esophageal mucosa at the various time intervals. The results of this work are similar to those reported previously for the gastric mucosa, the duodenal mucosa and the colonic mucosa of rats subjected to the same stressors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cervical esophageal web associated with a patch of heterotopic gastric mucosa

Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed.     

Gastric mucosa after partial gastrectomy

A partial gastrectomy of Billroth I or II type was performed in a series of 146 patients with peptic ulcer. Gastric biopsy was carried out two years later and the histology of the specimens compared with that of the body mucosa at the time of operation. In 138 patients without body atrophic gastritis (AG) before operation this condition was found in 74 (54%) two years after (46% of DU patients and 73% of GU patients). Those with antral or pyloric canal ulcers were particularly liable to develop AG (81%). Apart from site of ulcer various other factors possibly associated with the development of AG were examined: no positive correlations were found with the possible exception of anaemia. Gastric parietal cell antibodies were not found in any patient with AG tested. The cause of gastritis after partial gastrectomy and its possible relationship with gastric carcinoma are discussed.     

Hydroxyurea synchronization of cellular proliferation in the esophageal epithelium of mice with tumors

The synchronizing effect of hydroxyurea on the passage of the esophagus epithelia cells through the stage of the DNA synthesis and mitosis was investigated in albino mice bearing sarcoma. Dinrnal variations in the number of epithelial cells at these stages of the mitotic cycle were taken into consideration. Two mutually complementary indices for the measurement of the shifts in the cell population and the rate of the synchronization are used. Two cell groups which passed the S-phase and mitosis synchronously were found in artificial synchronization in the esophageal epithelium. The synchronization indices characterizing the first group were lower than control. In the second group the cell count during the DNA synthesis was double as compared with the number of cells synthesizing DNA in natural synchronization; however, the rate of the changes in the synchronism was the same in the experimental and control groups.     

Clonal heterogeneity in human esophageal squamous cell carcinomas on DNA analysis

Cancers are thought to arise through multistep accumulation of somatic mutations in the progeny of a single cell. Multiple mutations may induce molecular intratumor heterogeneity. Therefore, we examined molecular clonal heterogeneity in esophageal squamous cell carcinomas. Twenty-four esophageal squamous cell carcinomas and associated lymph node metastases were examined for microsatellite alterations, and abnormalities of the p53 and transforming growth factor-beta type II receptor (TGF-beta RII) genes. There were eight cases (33%) showing different patterns of loss of heterozygosity in primary tumors and metastatic lymph nodes with microsatellite markers. On the other hand, the abnormalities of p53 were identical in all these cases. No mutation was detected in the simple repeated sequences of the TGF-beta RII gene. These results indicate that molecular clonal heterogeneity exists in esophageal squamous cell carcinomas. Therefore, care is necessary in preoperative genetic diagnosis using biopsy samples.     

Biological characteristics of esophageal squamous cell carcinoma associated with contiguous intraepithelial carcinoma

To evaluate the biological significance of esophageal squamous cell carcinoma that is associated with contiguous intraepithelial carcinoma, we analyzed 95 patients with operated esophageal carcinoma. Of these 95 patients, eight had in situ carcinoma. Among 87 cases in which the tumo had invaded more deeply than the lamina propria, there were 42 cases (48.3%) of contiguous intraepithelial carcinoma associated with the main tumor. The biological characteristics (proliferative activity of cells, as revealed by immunostaining with the Ki-67 monoclonal antibody) of 45 tumors without contiguous intraepithelial carcinoma (group A) were compared with those of 42 tumors with contiguous intraepithelial carcinoma (group B). The more advanced was the main lesion, the lower was the incidence of contiguous intraepithelial carcinoma. The mean Ki-67 score of the main tumors in group A was 51.6% and that of the main tumors in group B was 45.9%. The mean Ki-67 score of the main tumors in group B was very similar to that of the contiguous intraepithelial carcinomas that were associated with the main tumors (44.4%, P = 0.682). Furthermore, the mean Ki-67 score of contiguous intraepithelial carcinomas associated with main tumors was very similar to that of carcinomas in situ (41.2%, P = 0.529). From our results, it is suggested that tumors with high proliferative activity may be assumed to grow rapidly and, as a result, the region of intraepithelial carcinoma may develop into an invasive tumor. By contrast, tumors with low proliferative activity may grow slowly and, in such cases, the carcinoma may remain in the epithelium around the invasive tumor.     

Skeletal metastases and bone marrow infiltration from squamous cell carcinoma of the buccal mucosa

Distant metastasis from head and neck cancer is an extremely rare phenomenon. Squamous carcinomas of the buccal mucosa is not known to spread to distant organs. We report a case of buccal mucosal carcinoma with biopsy proven metastasis to bone and bone marrow.     

Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.