Barrett's intestinal metaplasia (BIM) may harbor genomic mutations before the histologic appearance of dysplasia and cancer and requires frequent surveillance. We explored next-generation sequencing to detect mutations with the analytical sensitivity required to predict concurrent high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus by testing nonneoplastic BIM. Formalin-fixed, paraffin-embedded (FFPE) routine biopsy or endoscopic mucosal resection samples from 32 patients were tested: nonprogressors to HGD or EAC (BIM-NP) with BIM, who never had a diagnosis of dysplasia or EAC (N = 13); progressors to HGD or EAC (BIM-P) with BIM and a worse diagnosis of HGD or EAC (N = 15); and four BIM-negative samples. No mutations were detected in the BIM-NP (0 of 13) or BIM-negative samples, whereas the BIM-P samples had mutations in 6 (75%) of 8 cases in TP53, APC, and CDKN2A (P = 0.0005), detected in samples with as low as 20% BIM. We found that next-generation sequencing from routine FFPE nonneoplastic Barrett's esophagus samples can detect multiple mutations in minute areas of BIM with high analytical sensitivity. Next-generation sequencing panels for detection of TP53 and possibly combined mutations in other genes, such as APC and CDKN2A, may be useful in the clinical setting to improve dysplasia and cancer surveillance in patients with Barrett's esophagus.
The case of a 57-year-old woman admitted with symptoms and signs suggesting an intestinal infection caused by Vibrio cholerae, and who also developed a clinical picture compatible with acute cholecystitis, is presented. Cholera was diagnosed by examining a fresh sample of stools and cultures. An abdominal sonogram disclosed signs of acute acalculous cholecystitis. She underwent cholecystectomy, and cultures of a clear fluid and a "milky" sediment found within the gallbladder were also positive for V. cholerae. This microorganism was seen at the gallbladder mucosa microscopically. The strain was serotyped V. cholerae 01 (El Tor) Ogawa and was the etiology of the acute acalculous cholecystitis in this patient.
25 Background: In Europe, Asia, and North America, studies have identified that approximately 20% of patients with gastric adenocarcinoma exhibit overexpression of HER2/neu. This group of patients has been shown to benefit from combination therapy with the anti-HER2/neu monoclonal antibody trastuzumab. These findings have not been studied in Hispanics who may possess a distinct gastric cancer genotype. The aim of this study is to determine the rate of HER2/neu positivity in a completely Hispanic population with gastric adenocarcinoma and to analyze the clinical factors associated with HER2/neu. Methods: We conducted a retrospective study in three different hospitals in Monterrey, Mexico. The study population consisted of Hispanic patients with gastric adenocarcinoma who have had a gastric resection and for whom there were adequate amounts of tissue available in paraffin blocks. Tissue was tested for HER2/neu using both Immunohistochemistry (IHC) and the fluorescent in situ hybridization (FISH) techniques. Results: From 2000 to 2010, we initially evaluated 27 gastric cancer tumor samples. Sex distribution was 15 males and 12 females with a mean age of 57±15 (SD) years. Anatomic distribution of tumor was 4% in the cardias, 40% in the body and 56% in the antrum. Lauren's histological type distribution was 52% diffuse and 48% intestinal. Fifty-three percent of the tumors were high grade and nodal positivity was present in 69%. Overexpression of Her-2/neu (IHC ++ and +++) was found in five (17.4%) of the samples, being moderate (++) in two (7.4%) and strong (+++) in three (11%) tumor samples. FISH amplification for the HER2/neu gene was found in two (7.4%) tumors and was only seen in samples with a strong (+++) IHC result. There was no association identified between HER2/neu status with age, gender, degree of differentiation, T stage, or nodal status. Conclusions: In a homogeneous Hispanic population, 17.4% of gastric cancer patients were found to overexpress HER2/neu by IHC. FISH did not identify any additional HER2/neu positive tumors. It is important to consider IHC testing for HER2/neu in Hispanic gastric cancer patients as they could benefit from a chemotherapy regimen containing trastuzumab. No significant financial relationships to disclose.
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