Person:

Mashimo, Hiroshi

Objective: To investigate the clinicopathological features of columnar-lined esophagus (CLE) in Chinese patients. Methods: Among 182 consecutive resections of proximal gastric cancer with residual esophageal tissue, 114 were eligible for the study. The maximal lengths of CLE and superficial esophageal glands (SEG) and the presence or absence of chronic inflammation (CI), lymphoid follicles (LF), Helicobacter pylori (H. pylori) infection, intestinal metaplasia (IM), pancreatic metaplasia (PM) and dysplasia were analyzed and compared with those in the adjacent proximal gastric mucosa. Results: SEG were present in 110 cases with a mean length of 5.4 mm (range 1–16 mm, 90% equal to or under 10 mm and 10% between 11–16 mm). These glands were associated with CI (95%), LF (85%), H. pylori infection (42%), IM (25%), PM (36%) and dysplasia (10%). CLE was found in 65% of the cases and was associated with SEG (mean length of 4.0 mm, range 1–13 mm, 97% within 10 mm and 3% between 11–13 mm). The frequencies of CI (97%), LF (86%), H. pylori infection (65%) and PM (46%) in CLE were similar to those in the proximal stomach (CI 90%, LF 54%, H. pylori infection 58%, PM 39%). In contrast, the frequencies of IM (37%) and dysplasia (15%) in CLE were significantly lower than those in the proximal stomach (66% and 31%, respectively; P < 0.01). Conclusions: CLE in Chinese patients was within 10 mm in length in 97% of cases, and with SEG and H. pylori infection-related changes similar to those in the proximal stomach.

AIM: To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE). METHODS: Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009. Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE. Each tumor was re-staged, following the guidelines on esophageal adenocarcinoma, according to the 7th edition of the American Joint Commission on Cancer Staging Manual. All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features, i.e., age, gender, Helicobacter pylori (H. pylori) infection, surgical modality, Siewert type, tumor Bormann's type, size, differentiation, histology type, surgical margin, lymphovascular and perineural invasion, and pathologic stage in relation to survival after surgical resection. Prognostic factors for overall survival were assessed with uni- and multi-variate analyses. RESULTS: Patients' mean age was 65 years (range: 47-90 years). The male: female ratio was 3.3. The 1-, 3- and 5-year overall survival rates were 87%, 61% and 32%, respectively. By univariate analysis, age, male gender, H. pylori, tumor Bormann's type, size, histology type, surgical modality, positive surgical margin, lymphovascular invasion, and pT stage were not predictive for overall survival; in contrast, perineural invasion (P = 0.003), poor differentiation (P = 0.0003), > 15 total lymph nodes retrieved (P = 0.008), positive lymph nodes (P = 0.001), and distant metastasis (P = 0.005) predicted poor post-operative overall survival. Celiac axis nodal metastasis was associated with significantly worse overall survival (P = 0.007). By multivariate analysis, ≥ 16 positive nodes (P = 0.018), lymph node ratio > 0.2 (P = 0.003), and overall pathologic stage (P = 0.002) were independent predictors for poor overall survival after resection. CONCLUSION: Patients with PGCE showed worse overall survival in elderly, high nodal burden and advanced pathologic stage. This cancer may be more accurately staged as gastric, than esophageal, cancer.

In Western countries, distal esophageal adenocarcinoma has outnumbered squamous cell carcinoma because of a dramatic increase in the prevalence of columnar-lined esophagus. Because the relative prevalence of these diseases remains unknown in China, we investigated the histopathology of distal esophageal neoplasm in resection specimens from a high-volume medical center in China. A computerized search of esophageal cancer was conducted in the pathology database between 2004 and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal junction were retained for analysis. Pathology reports were reviewed along with medical, radiologic, and endoscopic records. All histology slides of selected cases were reevaluated (median, 13 per case). Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma were categorized according to the World Health Organization classification of esophageal cancers. The presence of columnar-lined esophagus and other pathologic changes were assessed in cases with residual esophageal mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1% of the cases, respectively. Synchronous carcinomas were found in 12% and consisted of primarily squamous cell carcinoma (50%) and proximal gastric adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases, among which intestinal metaplasia was present in 30% and low-grade dysplasia in 7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide histopathologic spectrum with predominant squamous cell carcinoma and rare esophageal adenocarcinoma. Although common, columnar-lined esophagus appears pathogenetically insignificant for most distal esophageal carcinomas.

Background: The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods: To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results: Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions: The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.