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Huang, Qin

Two main nonsurgical endoscopic approaches for ablating dysplastic and early cancer lesions in the esophagus have gained popularity, namely, radiofrequency ablation (RFA) and cryospray ablation (CSA). We report a uniquely suited endoscopic and near-microscopic imaging modality, three-dimensional (3D) optical coherence tomography (OCT), to assess and compare the esophagus immediately after RFA and CSA. The maximum depths of architectural changes were measured and compared between the two treatment groups. RFA was observed to induce 230~260 μm depth of architectural changes after each set of ablations over a particular region, while CSA was observed to induce edema-like spongiform changes to ~640 μm depth within the ablated field. The ability to obtain micron-scale depth-resolved images of tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess treatment efficacy. Such information could be potentially used to provide real-time feedback for treatment dosing and to identify regions that need further retreatment.

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.

Gastric Antral Vascular Ectasia (GAVE) may be an enigmatic source of non-variceal upper GI bleeding associated with various systemic diseases such as connective tissue disorders, liver disease, and chronic renal failure. Successful treatment of GAVE continues to be a challenge and has evolved through the years. Currently, given the rapid response, safety, and efficacy, endoscopic ablative modalities have largely usurped medical treatments as first-line therapy, particularly using argon plasma coagulation. However, other newer ablative modalities such as radiofrequency ablation, cryotherapy, and band ligations are promising. This paper is an overview of GAVE and its various endoscopic and medical therapies.

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.

Early gastric carcinoma (EGC) in Chinese patients remains poorly understood and endoscopic therapy has not been well established. Here, we compared endoscopic and clinicopathologic features between early proximal gastric carcinoma (PGC, n = 131) and distal gastric carcinoma (DGC, n = 307) in consecutive 438 EGCs diagnosed with the WHO criteria. By endoscopy, PGCs showed protruding and elevated patterns in 61.9%, while depressed and excavated patterns in 33.6%, which were significantly different from those (32.6% and 64.5%) in DGCs. PGCs were significantly smaller (1.9 cm in average, versus 2.2 cm in DGCs), invaded deeper (22.9% into SM2, versus 13% in DGCs), but had fewer (2.9%, versus 16.7% in DGCs) lymph node metastases. Papillary adenocarcinoma was significantly more frequent (32.1%, versus 12.1% in DGCs), as were mucinous and neuroendocrine carcinomas, carcinoma with lymphoid stroma (6.9%, versus 1.6% in DGCs); but poorly cohesive carcinoma was significantly less frequent (5.3%, versus 35.8% in DGCs). The overall 5-year survival rate was 92.9% in EGCs, and PGC patients showed shorter (42.4 months, versus 48.3 in DGCs) survival. Papillary and micropapillary adenocarcinomas and nodal metastasis were independent risk factors for worse survival in EGCs. EGCs in Chinese were heterogeneous with significant differences in endoscopy and clinicopathology between PGC and DGC.

SummaryClinicopathological characteristics of small gastric carcinoma have not been well defined in Chinese patients. The aim of this study was to investigate and compare small proximal (PGC, n = 111) with distal (DGC, n = 202) gastric carcinoma in 313 consecutive surgically resected small (≤2 cm) gastric carcinomas diagnosed with the WHO criteria. PGC patients were significantly older (average age 63 years versus 59 in DGCs) with a male/female ratio of 3:1. Most tumours were clustered along the lesser curvature (74% in PGCs and 65% in DGCs). Compared to DGCs, PGCs showed a protruded gross pattern significantly more frequently and were significantly better differentiated with a significantly wider histomorphological spectrum. Surprisingly, PGCs were composed of significantly fewer signet-ring cell carcinomas (1% versus 16% in DGCs) but were significantly more deeply invasive, compared to DGCs. Lymph node metastasis was detected in 23% overall, but was significantly less frequent in PGCs (16%) than in DGCs (26%) (p < 0.05). However, the difference in survival between the two groups was not statistically significant. Our results demonstrate that in Chinese patients, PGCs display distinct clinicopathological characteristics, compared to DGCs.

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+ cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+ cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.