Expression of alpha-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett's esophagus.
ABSTRACT Two different studies demonstrated alpha-methylacyl coenzyme A racemase (AMACR) to be a highly specific marker in Barrett's neoplastic lesions. Reactive atypia was positive in 3/30 cases in these studies. We present a retrospective study of early Barrett's adenocarcinoma treated with surgery (2000-2005, n=29; M:F=5:1, median age 67 years). We analyzed the role of AMACR expression in reactive and neoplastic lesions associated with the disease of 77 different specimens (60 biopsy and 17 surgical specimens) of these patients. In our cohort, 70% of cases demonstrated infiltration of the submucosa, 38% were poorly differentiated, and/or 31% demonstrated lymph vessel infiltration. We used a multi-tissue array, with reactive and neoplastic samples for each patient to analyze the immunoreactivity of AMACR. Barrett's epithelium that was negative for dysplasia and columnar epithelial cell changes indefinite for dysplasia (n=30) did not demonstrate AMACR immunoreactivity. AMACR immunoreactivity was demonstrated in 27% (8/30) of cases of Barrett's epithelium with columnar epithelial cell changes indefinite for dysplasia. Altogether 91% of cases with low-grade dysplasia were AMACR-positive and 96% of cases with high-grade dysplasia and early Barrett's adenocarcinoma were positive for AMACR. In summary, the sensitivity of AMACR expression in low-grade dysplasia and subsequent early Barrett's adenocarcinoma was significantly higher in our study compared with previous data. This might be a new diagnostic marker for dysplasia carcinoma sequence in Barrett's low-grade neoplastic lesions. Further studies are required to investigate this point with well-defined controls having at least 5-years follow-up.
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ABSTRACT: Double-balloon enteroscopy (DBE) is a new endoscopic tool that not only allows diagnostic workup of small bowel diseases, but also makes it possible to carry out therapeutic interventions. However, for a variety of reasons, endoscopic therapy appears to be more difficult to carry out deep in the small bowel than in the upper or lower gastrointestinal tract. The purpose of this study was to evaluate the acute technical success and acute complication rate of DBE. Between June 2003 and July 2006, 353 patients (152 women, 201 men; mean age 60.3 +/- 17.1 yr) with suspected or known small bowel disease underwent 635 consecutive DBE procedures. The majority of the patients were suffering from midgastrointestinal bleeding (N = 210, 60%). The overall diagnostic yield was 75% (265/353) for relevant lesions in the small bowel. The overall therapeutic yield was 67% (236/353). Endoscopic therapy was performed in 59% of these patients (139/236). All therapeutic interventions were done in an inpatient manner. The majority of the procedures were carried out with the patients under conscious sedation (N = 130, 73%); sedation with propofol was administered in 37 (20.8%) and with a combination of propofol and meperidine in 11 (6.2%) investigations. A total of 178 therapeutic procedures was carried out. A median of 270 cm of the small bowel was visualized using the oral route and a median of 150 cm using the anal route. The investigation time averaged 78 +/- 30 minutes. The endoscopic treatments included argon plasma coagulation (APC, 102 treatment sessions), injection therapy (N = 2), a combination of APC and injection (N = 6), polypectomies (N = 46), dilation therapy (N = 18), and foreign-body extraction (N = 3). In 6/178 cases (3.4%), polypectomy (N = 2), dilation (N = 3), and implantation of a self-expanding metal stent (N = 1) could not be performed successfully for technical or anatomical reasons. Severe treatment-associated complications occurred in six of the 178 therapeutic procedures (3.4%) and 4/139 patients (2.9%), consisting of bleeding (N = 2) and perforation (N = 3) during and after polypectomy of large polyps (>3 cm in size), as well as one case of segmental enteritis after APC. Endoscopic therapeutic interventions can be performed safely even in the more difficult conditions of the small bowel in the majority of patients. Polypectomy of large polyps appears to be the procedure associated with the highest risk.The American Journal of Gastroenterology 04/2007; 102(3):527-35. · 7.55 Impact Factor
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ABSTRACT: The need for extensive surgical resection for early-stage esophageal adenocarcinoma has been challenged by the increasing frequency of early detection in patients with Barrett's esophagus undergoing surveillance endoscopy. Limited endoscopic or surgical procedures are promoted as alternatives to radical esophagectomy and lymphadenectomy in such patients. Currently available data show that limited surgical resection of the distal esophagus with regional lymphadenectomy and interposition of an isoperistaltic jejunal segment is a safe and oncologically adequate procedure in this situation and provides good quality of life. This is in contrast to endoscopic ablation or endoscopic mucosal resection, which are associated with high tumour recurrence rates and persistence of premalignant Barrett esophagus. New technologies for accurate prediction of the presence and pattern of lymphatic spread-e.g. sentinel node techniques and artificial neural networks-may allow a further reduction of the invasiveness of surgical resection without compromising cure rates.Baillière' s Best Practice and Research in Clinical Gastroenterology 01/2006; 19(6):927-40. · 3.16 Impact Factor
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ABSTRACT: To correlate immunohistochemical expression patterns and prognosis in oesophageal adenocarcinoma. The expression of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor (EGFR) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples. The expression analysis on protein level was performed on routine paraffin wax-embedded material, with immunohistochemical staining of the samples, assembled on a tissue microarray. The results were correlated with clinicopathological features (pT, pN and G) and survival. 22 (16%) tumours showed an overexpression of the c-erbB-2 oncoprotein. Expression of EGFR was observed in 72 (55%) cases, accumulation of p53 in 68 (52%) cases and of cyclin D1 in 102 (77%) cases. Loss of p16INK4A expression was observed in 101 (76%) cases and low expression of p27KIP1 in 91 (71%) cases. Expression of these proteins did not correlate with tumour stage, grade, Lauren's or World Health Organization classification or lymph node status. On univariate survival analysis, more advanced tumour stage (p = 0.002), lymph node involvement (p = 0.003), high tumour grade (p = 0.017) and lack of EGFR expression (p = 0.034) were found to be associated with poorer survival. On multiple regression analysis, only tumour stage (p = 0.03) and lymph node involvement (p = 0.004) were shown to have an association with the survival of the patient. The immunohistochemical expression of c-erbB-2 oncoprotein, cylin D1, p16INK4A, p27KIP1, p53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity. None of the molecular markers assessed, however, was of prognostic value. Identification of any marker superior to or even approaching the prognostic value of conventional histopathological markers (pT and pN) was therefore not possible.Journal of Clinical Pathology 07/2006; 59(6):631-4. · 2.44 Impact Factor