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Oesophagogastric adenocarcinoma (EGA) includes oesophageal (EA), gastro-oesophageal junctional (GEJA), and gastric (GA) adenocarcinomas. The prognostic values of clinicopathological factors in these tumours remain obscure, especially for GEJA that has been inconsistently classified and staged. We studied the prognosis of EGA patients among the three geographic groups in 347 consecutive patients with a median age of 70 years (range 47-94). All patients were male, and 97.1% were white. Based on tumour epicentre location, EGAs were sub-grouped into EA (over 2 cm above the GEJ; n=3, 18.1%), GEJA (within 2 cm above and 3 cm below the GEJ; n=231, 66.6%), and GA (over 3 cm below the GEJ; n=53, 15.3%). We found that the median overall survival (OS) was the longest in EA (62.9 months), compared to GEJA (33.4), and GA (38.1) (p<0.001). Significant risk factors for OS included tumour location (p=0.018), size (p<0.001), differentiation (p<0.001), adenocarcinoma subtype (p<0.001), and TNM stage (p<0.001). Independent risk factors for OS comprised low-grade papillary adenocarcinoma [odds ratio (OR) 0.449, 95% confidence interval (CI) 0.214-0.944, p<0.05), mixed adenocarcinoma (OR 1.531, 95% CI 1.056-2.218, p<0.05), adenosquamous carcinoma (OR 2.206, 95% CI 1.087-4.475, p<0.05), N stage (OR 1.505, 95% CI 1.043-2.171, p<0.05), and M stage (OR 10.036, 95% CI 2.519-39.993, p=0.001)]. EGA was further divided into low-risk (common well-moderately differentiated tubular and low-grade papillary adenocarcinomas) and high-risk (uncommon adenocarcinoma subtypes, adenosquamous carcinoma) subgroups. In this grouping, the median OS was significantly longer in the low-risk (83 months) than in the high-risk (10 months) subgroups (p<0.001). In conclusion, the prognosis of EGA patients was significantly better in EA than in GEJA or GA and could be stratified into low and high-risk subgroups with significantly different outcomes., (Copyright © 2024 Royal College of Pathologists of Australasia. All rights reserved.)

Objective: To investigate the clinicopathological and prognostic significance of intestinal metaplasia (IM) in endoscopically resected early gastric carcinoma (EGC)., Methods: Altogether 136 consecutive cases with EGC resected by endoscopic submucosal dissection over 5 years were included and divided into the early gastric cardiac (EGCC; n = 60) and non-cardiac carcinoma (EGNCC; n = 76) groups. Goblet cell IM and subtypes were determined with histology and immunostaining. Recurrence-free survival (RFS) was compared among various IM groups., Results: IM was identified in 128 (94.1%) EGC cases, including complete IM (n = 39), incomplete IM (n = 27), and mixed IM (n = 62). Incomplete IM was significantly more common in EGCC and exhibited a lower frequency of en bloc resection than the complete subtype. The frequency of synchronous or metachronous gastric tumor was significantly more common in EGCC with complete IM than in those with incomplete IM. Compared to EGC without IM, EGC with IM showed a significantly higher frequency of non-poorly cohesive carcinoma, en bloc resection, and non-eCuraC-1 grade. EGNCC with IM was significantly associated with negative resection margins and en bloc resection. The 5-year RFS was significantly lower in EGNCC patients with incomplete IM compared with those with mixed IM. The independent risk factors for RFS included tumor size >2 cm and eCuraC-1 grade., Conclusions: Subtyping IM in EGC helped predict endoscopic resectability, prognosis, and risk of synchronous or metachronous gastric tumor. The significance of IM differed between EGCC and EGNCC. Large studies with longer follow-up are warranted to validate our findings., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Introduction: High risk of lymph node metastasis (LNM) in gastric papillary adenocarcinoma causes endoscopists to worry about the suitability of endoscopic resection for early gastric papillary adenocarcinoma (EPAC). We compared risk factors and attempted to establish a scoring system to stratify LNM risk in patients with EPAC., Methods: A retrospective analysis was performed on 2,513 patients with early gastric carcinoma (EGC) who underwent radical resection in 4 tertiary hospitals in China. Univariate and multivariate analyses were performed to compare the invasiveness in EPAC and other types of EGC and to evaluate potential factors in predicting LNM risk in EPAC groups., Results: Three hundred thirty-five patients with EPAC were enrolled in our study, of which 62 patients were found to have LNM. After comparing clinicopathological characteristics of EPAC with and without LNM, the following factors were included in the risk scoring system: 1 point each for lower stomach location and tumor size >2.0 cm, 3 points for lymphovascular invasion, and 4 points for submucosal invasion; the risk scoring system was validated in a small internal validation set with an area under the curve of 0.844., Discussion: Our results suggested that EPAC was highly invasive compared with other EGCs, especially differentiated EGC types, and need to be treated more rigorously. This proposed risk scoring system could stratify LNM risk in patients with EPAC, and endoscopic resection may only be performed safely on the groups with a low LNM rate., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Gastric cancer (GC) is a heterogeneous disease; the tumor distribution and molecular subtype could affect the prognosis of patients with GC. However, the clinicopathological difference between GC in the lesser and that in the greater curvature remains unknown. In this study, we aimed to investigate the difference and provide new clues for the treatment of GC. Between January 2010 and August 2014, 1249 consecutive patients with GC in the lesser or greater curvature were treated in our surgery department; data related to the demographic characteristics, pathological type, tumor grade, tumor size, TNM stage, tumor markers, operative methods, complications, and follow-up were retrospectively analyzed using a univariate analysis and the Kaplan-Meier method. The tumor size in lesser curvature was larger than that in the greater curvature (4.95 ± 2.57 vs 4.43 ± 2.62 cm, P = .034); patients with GC in the lesser curvature had a higher incidence of total gastrectomy and a lower incidence of distal gastrectomy than those with GC in the greater curvature (60.2% vs 43.2%, and 34.8% vs 49.2%, P = .002). No significant differences were found in the 5-year survival rate between patients with GC in the greater curvature and those with GC in the lesser curvature (62.6% vs 66.1%, P = .496). The epidermal growth factor receptor (EGFR) expression rate of tumors in the lesser curvature was 40.55%, which was significantly higher than that of tumors in the greater curvature (25.92%, P = .024), while the 5-year survival rate of patients with EGFR-positive expression was 50.8%, which was significantly lower than that of patients with EGFR-negative expression (64.8%, P = .021). Significant differences were observed in the clinicopathological features between GC in the lesser curvature and that in the greater curvature. These differences contribute to the improvement in the treatment outcome., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Papillary early gastric carcinoma (EGC) is believed to have a low risk of lymph node metastasis (LNM) and thus can be resected endoscopically. We observed anecdotally that some papillary EGC tumors showed conspicuous high-grade dysplastic features, but the significance of these observations is unknown. In this bicenter study we investigated papillary EGCs that were divided into high-grade (n=96) and low-grade (n=118) groups among 1136 consecutive EGC radical resection cases. Concurrent 464 well-moderately differentiated tubular EGCs were served as the control group. Compared with low-grade papillary and well-moderately differentiated tubular EGCs, high-grade papillary EGC displayed significantly larger sizes (mean 2.51 cm), higher frequencies of the elevated macroscopic type (51%), lymphovascular invasion (LVI) (38.5%), and LNM (31.2%). Low-grade papillary EGCs exhibited a higher prevalence of the elevated macroscopic type, but not LVI nor LNM, compared with tubular EGC. Independent risk factors for LNM included high-grade histology, female sex, distal location, submucosal invasion, and LVI. The 5-year overall survival rate was significantly lower in high-grade (79.6%) papillary than in low-grade (88.9%) papillary or tubular (92.8%) EGCs, while no significant difference in prognosis was observed in the latter 2 groups. Age of 66 years or older and LNM were independent risk factors for overall survival. In conclusions, high-grade papillary EGC was associated with high frequencies of LVI, LNM, and poor prognosis, and thus unsuitable for endoscopic therapy, while low-grade papillary EGC showed clinicopathologic features and prognosis similar to well-moderately differentiated tubular EGC and may be treated endoscopically in appropriate clinical settings., Competing Interests: Conflicts of Interest and Source of Funding: Supported by a research grant from the Youth Talents Program of the Health Commission of the Changzhou City (QN201935 to Yuqing Cheng) and a research grant from the Recruited Foreign Talents Program of the Science and Technology Bureau of the Changzhou City (CQ20204036 to Yuqing Cheng) in China. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment for early gastric cardiac cancer (EGCC). Here, we investigate the clinical outcomes of the EGCC patients who underwent ESD in different indications., Methods: From January 2011 to October 2019, we enrolled 502 EGCC lesions from 495 patients which were resected by ESD at our center. We retrospectively analyzed the short-term and long-term clinical outcomes among different indication groups., Results: The number of the patients in the absolute indication (AI), expanded indication (EI) and beyond the expanded indication (BEI) groups was 265, 137 and 93, respectively. The en bloc resection rate was 100%, 100% and 98.9% (P = 0.185). The complete resection rate was 99.3%, 98.5% and 74.5%, respectively (P < 0.001). During a median follow-up of 48.1 months, the lymph node metastasis rate was 0%, 0% and 2.3% (P < 0.001). The distant metastasis rate was 0.4%, 0% and 2.3% (P = 0.150). The five-year disease-specific survival rate in the BEI group was 96.6% (P = 0.016), compared to 99.6% in the AI group and 100% in the EI group., Conclusion: The efficacy for ESD patients in EI group was almost equal to the AI group. Patients in the BEI group showed generally favorable clinical outcomes and needed to be carefully checked after ESD. ESD may be an optional treatment for patients unsuitable for gastrectomy.

Aim and Background: The aim of this study was to compare the efficacy and safety between endoscopic full-thickness resection (EFR) and laparoscopic or surgical resection methods for gastric gastrointestinal stromal tumor (GIST) in size of 5.0 cm or less. Gastric GISTs are common, and resection is the most effective treatment., Method: We retrospectively reviewed 216 resections of gastric GISTs in size of up to 5.0 cm at our center from 2009 to 2017.Eligible resection cases were divided into EFR (n = 85), laparoscopic(n = 64), and surgical (n = 67) groups. The clinical records, patient demographic, symptoms, perioperative data, pathological findings, and long-term follow-up outcomes were collected and compared statistically., Results: No tumor rupture or recurrence occurred in the three groups. The prevalence of complications was significantly lower in EFR (5.9%) than both laparoscopic (7.8%) and surgical group (16.4%) (P < 0.01). In EFR group, the R0 resection rate (95.3%) was significantly lower than in the laparoscopic group and surgical group (100%) (P < 0.001). The hospital cost (OR = 62.79, CI: 12.954-304.363, P < 0.0001) were significantly lower in the EFR than in the laparoscopic group. The hospital cost (OR = 39.032, CI: 8.045-189.371, P < 0.0001) and post-operative diet time (OR = 2.779, CI: 1.225-6.304, P < 0.05) were also significantly lower in the EFR than in the surgical group., Conclusion: EFR was a feasible treatment for gastric GISTs of size of ≤ 5.0 cm with an acceptable complete resection rate. In addition, EFR had significantly fewer postoperative complications, shorter length of hospital stay, and lower cost.

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Early gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus-corpus and antrum-angularis-pylorus subgroups, especially between EGCC with and without oesophageal invasion., Methods: In this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs., Results: Compared to the EGNCC antrum-angularis-pylorus (n = 181), but not fundus-corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum-angularis-pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation., Conclusions: There exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.

Background: Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. Therefore, we collected EBV-GCLS cases and studied clinicopathology and prognosis., Methods: By a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into intramucosal, SM1, and SM2 subgroups. The latter 2 subgroups were classified according to the submucosal invasion depth below or over 500 μm., Results: All 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was significantly more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not with age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons in the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that in conventional early gastric carcinomas (p < 0.05) and the 5-year survival rate of patients with EBV-GCLS was better than that with conventional early gastric carcinomas in 3 subgroups (100% vs 91.5, 85.7, 83.9%, respectively), although the differences did not reach a statistically significant level due to the small sample size. Significant differences among 4 subgroups were found in tumor grade, lymphovascular invasion, LNM, pathological stage, and synchronous tumor, but not in age, gender, macroscopic type, tumor size, location, perineural invasion., Conclusions: Even with poor differentiation and SM2 invasion, EBV-GCLS showed very low risk of LNM and may be a candidate for endoscopic therapy such as endoscopic submucosal dissection.

Compared with early gastric intramucosal carcinoma, submucosal carcinoma is known to have a higher risk for lymph node metastasis (LMN), but risk factors in submucosal carcinoma remain elusive. In this multicenter study with 621 radical gastrectomies for submucosal early gastric carcinoma, we investigated tumor budding and other risk factors of LMN that were identified in 172 cases (27.7%). Overall, independent high-risk factors for LMN included lymphovascular invasion (odds ratio, 3.9; 95% confidence interval, 2.5-6.1), tumor budding (odds ratio, 3.3; 95% confidence interval, 1.9-5.9), mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma (odds ratio, 2.1; 95% confidence interval, 1.0-4.3), and female sex (odds ratio, 1.6; 95% confidence interval, 1.0-2.6), whereas gastric cardiac submucosal carcinomas had a significantly lower risk for LMN (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). In 276 well/moderately differentiated tubular or papillary submucosal early gastric carcinomas, independent risk factors were tumor budding (odds ratio, 3.7; 95% confidence interval, 1.6-8.7), deep submucosal (SM2) invasion (odds ratio, 3.1; 95% confidence interval, 1.3-7.6), and lymphovascular invasion (odds ratio, 2.7; 95% confidence interval, 1.3-5.6). In 174 cases without tumor budding and lymphovascular invasion, no LMN was identified in 47 cardiac tumors, and 15 tumors <1.0 cm in size. In conclusion, tumor budding, lymphovascular invasion, mixed tubular/papillary adenocarcinoma with poorly cohesive carcinoma, and female gender were found to be significant high-risk factors for LMN in submucosal early gastric carcinoma, while submucosal gastric cardiac carcinoma had a significantly lower risk for nodal metastasis.

Clinicopathology and risk factors of lymph node metastasis (LNM) in micropapillary early (pT1) gastric carcinoma (MEGC) remain elusive because of the extreme rarity. In this multicenter study, we investigated 1890 consecutive radical resections of early gastric carcinoma diagnosed with the World Health Organization criteria and identified 29 (1.5%) MEGC cases with a small (≥5%) micropapillary component. MEGC showed a male predominance (male-to-female ratio, 21:8). Most (93.1%; 27/29) tumors invaded submucosa. Lymphovascular invasion was detected in 14 (48.3%) of 29 cases. LNM was found in 13 cases (44.8%; 11 identified with a routine hematoxylin-eosin stain and 2 additional cases with a positive pancytokeratin immunostain). Overall, independent risk factors for LNM in early gastric carcinoma included patient age of 62 years or less, female sex, noncardiac location, ulcerative pattern, tumor size of greater than 2 cm, submucosal invasion, Lauren diffuse type, lymphovascular invasion, and MEGC. In MEGC, advanced pathologic stages were demonstrated in 6 (20.7%) of 29 cases. The 5-year overall survival rate of MEGC patients was 58.6%. Submucosal invasion, lymphovascular invasion, and LNM were significantly more frequent in the MEGC group than in the non-MEGC groups. Advanced pathologic stages were significantly more common in MEGC than in nonmicropapillary Lauren intestinal- but not diffuse-type early gastric carcinomas. In conclusion, MEGC demonstrated a high propensity for lymphovascular invasion, LNM with advanced stages, and dismal prognosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Gastric cancer is common in China. At present, early detection with prompt resection of early gastric carcinoma (EGC) is crucial for improving patient's survival. Because of high heterogeneity of EGC in Chinese patients we reviewed recent clinicopathological and molecular evidence and proposed a grouping EGC in three subgroups according to their location for appropriate management. In group 1 (cardia), most patients with EGC in this small location were elderly men. The tumors originated in the cardiac mucosa with a high proportion of cases with slightly elevated gross patterns and intestinal adenocarcinoma histology with moderate to well differentiation. Poorly cohesive carcinoma was infrequent. As the risk for lymph node metastasis in this kind of tumor was significantly lower than that in the distal stomach, endoscopic therapy is preferred. Group 2 (fundus-corpus), many patients with EGC in this large location were young women. The EGCs originated in the oxyntic mucosa with pure and mixed poorly cohesive carcinomas that are more commonly present in this area than in any other. Most tumors were poorly differentiated with a high risk for lymph node metastasis. Thus, endoscopic therapy may be appropriate for intramucosal, but not for submucosal, carcinoma. Group 3 (antrum-pylorus). EGC tumors arose from the antral mucosa, primarily because of Helicobacter pylori infection, following the Correa gastric cancer tumorigenetic pathway. Erosive and ulcerated gross patterns were most frequently observed. While most EGCs in this location were mainly intestinal adenocarcinomas, poorly differentiated EGCs were substantial in number. Because the risk of lymph node metastasis remains to be illustrated, clinical management requires an individualized approach. This preliminary observation requires verification in large nationwide multicenter studies., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in a Chinese population., Methods: The data were analyzed to determine risk factors of LNM. The patients' characteristics, the tumor's location, gross features, histological type, differentiation, invasive depth, lymphovascular invasion (LVI), perineural invasion and the numbers of lymph nodes retrieved and involved were statistically analyzed., Results: A total of 734 patients with EGC were finally enrolled in the study, and LNM was present in 14.2% (104/734) of them. By univariate analysis, significant risk factors for LNM included depressed or excavated gross patterns, size ≥1.0 cm, SM2, moderate/poor differentiation, histological type of hepatoid or micropapillary adenocarcinoma, LVI, perineural invasion and tumor necrosis. By multivariate analysis, independent risk factors for LNM were size ≥3.0 cm (odds ratio [OR] 4.9), SM2 (OR 2.4), moderate (OR 3.6) and poor (OR 5.0) differentiation, LVI (OR 3.1) and tumor necrosis (OR 1.7). Early gastric cardiac carcinoma (OR 0.3) had a significantly lower risk than non-cardiac carcinoma. No LNM was identified in 67 EGC of <1.0 cm in size and without poor differentiation, in 142 intramucosal EGC cases of smaller than 2.0 cm and without poor differentiation, in 129 cases of well-differentiated EGC without deep SM2 submucosal invasion, or in 54 intramucosal EGC located in the gastric cardia., Conclusion: Independent risk factors for LNM in EGC include tumor size ≥3.0 cm, SM2 invasion, moderate/poor differentiation, LVI and tumor necrosis. Early cardiac carcinoma had a significantly lower risk of LNM than non-cardiac EGC., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Clinical decision-making on endoscopic vs. surgical resection of early gastric cardiac carcinoma remains challenging because of uncertainty on risk of lymph node metastasis. The aim of this multicenter study was to investigate risk factors of lymph node metastasis in early gastric cardiac carcinoma. Guided with the World Health Organization diagnostic criteria, we studied 2101 radical resections of early gastric carcinoma for risk factors associated with lymph node metastasis, including tumor location, gross pattern, size, histology type, differentiation, invasion depth, lymphovascular, and perineural invasion. We found that the risk of lymph node metastasis was significantly lower in early gastric cardiac carcinomas (6.7%, 33/495), compared with early gastric non-cardiac carcinomas (17.1%, 275/1606) (p < 0.0001). In early gastric cardiac carcinoma, no lymph node metastasis was identified in intramucosal carcinoma (0/193) and uncommon types of carcinomas (0/24), irrespective of the gross pattern, size, histologic type, differentiation, and invasion depth. Ulceration, size > 3 cm, and submucosal invasion were not significant independent risk factors for lymph node metastasis. In 33 early gastric cardiac carcinomas with lymph node metastasis, either lymphovascular invasion or poor differentiation was present in 16 (48.5%) cases and together in six cases. By multivariate analysis, independent risk factors of lymph node metastasis in early gastric cardiac carcinoma included lymphovascular invasion (Odds Ratio (OR): 7.6, 95% Confidence Interval (CI): 2.8-20.2) (p < 0.0001) and poor differentiation (OR: 6.0, 95% CI: 1.4-25.9) (p < 0.05). In conclusion, lymph node metastasis was not identified in early gastric cardiac intramucosal carcinoma and uncommon types of carcinoma. The risk of lymph node metastasis was also significantly lower in tumors with submucosal invasion, especially for cases without lymphovascular invasion or poor differentiation. These results lend support to the role of endoscopic therapy in the treatment of patients with early gastric cardiac carcinoma.

Carcinosarcoma is a rare malignant neoplasm, consisting of both epithelial and mesenchymal component. Primary gastric carcinosarcoma is rare and poorly understood. We reported clinicopathologic features of 4 cases and analysis of 76 cases published in the literature. Clinical symptoms were nonspecific with epigastric pain, weight loss, and melena, as the most common complaints. The prognosis of patients was dismal with high mortality. The tumor commonly occurred in the upper stomach in Chinese patients, whereas, it was more prevalent at the lower stomach in Japanese and other populations. The two malignant components of this rare cancer showed considerable histological heterogeneity with a wide range of differentiation. We propose that carcinosarcomas be divided in two main subtypes: conventional carcinosarcoma and carcinosarcoma, not-otherwise-specified (NOS). Such distinction may provide useful information for targeted treatment of various sarcomatous components of this tumor. Immunohistochemistry should be routinely applied in the diagnosis of this rare tumor.

Objective: To investigate risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in four tertiary medical centers in Jiangsu Province, China., Methods: Among 10 097 consecutive combined gastric cancer radical resections, 1903 EGC were identified and reviewed, 283 excluded and 1620 included in the study. All pathological and some endoscopic reports were reviewed for patients' characteristics, tumor location, gross features, and the number of lymph nodes retrieved and involved. Two pathologists independently investigated the pathological features of tumor type, differentiation, invasion depth, lymphovascular invasion (LVI), and perineural invasion. The data were statistically analyzed to identify risk factors for LNM., Results: The average number of lymph nodes retrieved was 17.5 per patient. LNM was diagnosed in 15.5%. By univariate analysis, significant risk factors for LNM included age ≥ 41 years, female sex, size over 1 cm, submucosal invasion, poor differentiation, poorly cohesive carcinoma, micropapillary adenocarcinoma, adenocarcinoma mixed with signet-ring cell carcinoma, LVI, perineural invasion, and distal gastric location. By multivariate analysis, independent risk factors for LNM were size ≥ 3 cm (odds ratio [OR] 1.9), poor differentiation (OR 2.5), adenocarcinoma mixed with signet-ring cell carcinoma (OR 1.7), LVI (OR 5.8) and submucosal invasion (OR 2.9). In contrast, size < 3 cm and ulcer were not significant risk factors. Early cardiac carcinoma (OR 0.4) had significantly lower risk., Conclusions: Independent risk factors for LNM in EGC in Chinese patients included tumor size ≥ 3 cm, poor differentiation, submucosal invasion, adenocarcinoma mixed with signet-ring cell carcinoma and LVI. Early cardiac carcinoma had a significantly lower risk for LNM., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

As a cancer stem cell marker, CD44 variant 6 (CD44v6) has been implicated in carcinogenesis, tumor progression, and metastasis in a variety of human carcinomas. However, little is known about the expression of CD44v6 in Gastric Carcinoma (GC). Therefore we investigated CD44v6 expression in clinical specimen and further explore the underlying molecular mechanisms.In this study, we systemically investigated CD44v6 expression by immunohistochemistry in normal, premalignant gastric mucosa (low and high grade intraepithelial neoplasia), and GC at various stages. The correlation of CD44v6 expression with clinicopathological characteristics, and prognosis in GC was also analyzed. Next, we investigated cell proliferation, migration and invasion in GC cell lines. Furthermore, we explored a novel mechanism by which CD44V6 was upregulated in GC cell.The immunohistochemistry results showed that enhanced expression of CD44v6 was closely associated with tumor differentiation, lymph node metastasis, TNM stage and poor prognosis in GC patients. In gastric cancer cell lines, CD44v6 involved in cell proliferation, invasion and metastasis in Next, report on a novel mechanism by which interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling up-regulates expression of CD44v6. RNA interference silencing of STAT3 resulted in decrease of CD44v6 levels. We also found that STAT3 inhibitor AG490 decrease expression of CD44v6 by blocking activation of STAT3, even in the presence of IL-6. Targeting STAT3-mediated CD44v6 up-regulation may represent a novel, effective treatment by eradicating the stomach tumor microenvironment.

Gastric cardiac carcinoma (GCC) was and is considered as a part of esophageal adenocarcinoma (EAC) and staged with the rules for EAC. This may change. Recent comprehensive integrated genomic investigations on gastric and esophageal carcinomas discovered similar chromosomal instability profiles in these two groups of carcinomas with a gradual increasing gradient from the lowest percentage in the distal gastric antrum to a high level in the proximal gastric cardia, and to the peak of almost 100% in EAC. Therefore, most GCCs and EAC share similar chromosomal instable features of gastric carcinoma and should be grouped as a single disease entity because EAC may be the proximal extension of chromosomal instable GCCs. This breakthrough discovery in genomic characteristics of GCC and EAC would dramatically change the strategy on how patients should be appropriately managed clinically and also greatly help future investigation on detailed molecular pathogenetic mechanisms of GCC, leading to cure this fatal cancer., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Early-onset gastric cancer (EOGC) is predominant in females, diffuse histology, and hereditary pattern. Germline mutation of CDH1 and p53 has been reported previously and female dominance was speculated to be associated with estrogen and its receptors. Expression of E-cadherin, estrogen receptor α (ERα), estrogen receptor β (ERβ), and p53 in EOGC remains unclear, which was the focus of this study, to assess clinical significance of their expression in EOGC. The expression of E-cadherin, ERα, ERβ, and p53 in tumors and normal tissues from surgically resected EOGCs was assessed by immunohistochemistry (n = 139) and Western blot (n = 7) methods, respectively. The expression in tumor tissues was significantly higher for ERα, ERβ, and p53, but lower for E-cadherin, compared to uninvolved mucosa. Positive staining of ERβ and p53 was more frequently observed in younger patients with advanced TNM stages. For E-cadherin, significant correlation was observed between the immunopositivity and TNM stages IA+IB. P53-negative patients had significantly better outcomes than p53-positive patients. Significant association between expression of E-cadherin and histologic types was found in familial, but not in sporadic, EOGC. In conclusion, our results demonstrated E-cadherin may have a role in initiation of EOGC and positive ERβ and p53 expression may partially explained early-onset and tumor progression of EOGC., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate risk factors of lymph node metastasis (LNM) in Chinese early gastric carcinoma (EGC) patients diagnosed using the World Health Organization (WHO) criteria and compare the differences in those factors between proximal (PGC) and distal gastric carcinoma (DGC)., Methods: Among 3 176 gastric cancer resections we identified 379 (11.9%) consecutive EGC (104 PGC and 275 DGC) with lymphadenectomy performed at the Affiliated Nanjing Drum Tower Hospital of Nanjing University (Nanjing, Jiangsu Province, China) between January 2005 and December 2012. Endoscopic and clinicopathological features related to LNM were analyzed., Results: LNM occurred in 49 (12.9%) EGC, including three PGC and 46 DGC. In early DGC, middle age (41-60 years), tumor size ≥3.1 cm, submucosal invasion, poorly cohesive carcinoma, micropapillary adenocarcinoma and lymphovascular invasion were risk factors by univariate analysis. In contrast, no risk factors of LNM were identified in early PGC. By multivariate analysis, female sex (odds ratio [OR] 2.4), DGC (OR 8.1), poorly cohesive carcinoma (OR 8.8) and lymphovascular invasion (OR 38.8) were found to be significant independent risk factors for LNM. The risk of LNM was effectively stratified using a scoring model of mild (score ≤3.5), moderate (score 4.0-8.5) and high (score ≥16) risk groups., Conclusions: LNM occurred in 12.9% of EGC diagnosed with the WHO criteria in Chinese patients. Independent risk factors of LNM were identified in early DGC only and included female sex, DGC, poorly cohesive carcinoma and lymphovascular invasion. Early PGC has a much lower risk for LNM than early DGC., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The American Joint Committee on Cancer (AJCC) staging scheme requires staging proximal gastric carcinoma (PGC) as esophageal adenocarcinoma (EAC), which has been shown to be controversial by recent research results. To update the current research findings on PGC, we systematically reviewed and analyzed the scientific evidence on key arguments related to PGC. The data of high-quality research articles showed that PGC arised in the cardiac mucosa in the proximal stomach within 3 cm below the gastroesophageal junction. Its incidence is rising in East Asian countries, but decreasing in the West, and plateaued at a low level in the United States. PGC is a slowly progressive cancer with unknown independent risk factors and the mechanisms of pathogenesis. This carcinoma exhibits a wide histopathological spectrum and heterogeneous post-resection patient survival characteristics, and cannot be adequately staged for prognotic stratification by the current AJCC staging classification. The results on PGC genomics reveal unique genetic profiles, especially in East Asian populations. In conclusion, mounting evidence defies a simple placement of PGC in a single category of EAC for disease classification; further investigations on the mechanisms of PGC pathogenesis are urgently needed., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Little is known about clinicopathological characteristics of gastric carcinoma (GC) in young (≤40 years) Chinese patients. We aimed in this study to analyze those features along with family history and prognostic factors after resection. We retrospectively reviewed all 4671 GC resections (surgical and endoscopic) performed at our center from 2004 to 2014 and identified 152 (3.2%) consecutive young patients. Patient demographics, clinical results, family history, and endoscopic-pathological findings were analyzed along with the older (>41 years) GC controls recruited in the same study period. Clinicopathological factors related to postresection outcomes were assessed statistically. The trend of GC resections in young patients was not changed over the study period. Compared to old GCs, the young GC cohort was predominant in women, positive family history, middle gastric location, the diffuse histology type, shorter duration of symptoms, and advanced stage (pIII+pIV, 53.3%). Radical resection was carried out in 90.1% (n = 137) with a better 5-year survival rate (70.3%) than palliative surgery (0%, n = 15). There was no significant difference in clinicopathological characteristics between familial GC (FGC, n = 38) and sporadic GC (SGC, n = 114) groups. Very young patients (≤ 30 years, n = 38) showed lower Helicobacter pylori (Hp) infection and significantly higher perineural invasion rates, compared to older (31-40 years) patients. Hp infection was more commonly seen in the Lauren's intestinal type and early pT stages (T1+T2). Independent prognostic factors for worse outcomes included higher serum CA 72-4, CA 125 levels, positive resection margin, and stage pIII-pIV tumors. The 5-year survival rate was significantly higher in patients with radical resection than those without. GCs in young Chinese patients were prevalent in women with advanced stages but showed no significant differences in clinicopathology between FGC and SGC groups. High serum CA 72-4 and CA 125 levels may help identify patients with worse outcomes. Radical resection improved postresection survival.

Clinicopathological 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.

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.

Objective: The incidence of proximal gastric carcinoma (PGC) is rising worldwide for unknown reasons. Herein we compare the risk factors of early PGC with distal gastric carcinoma (DGC) in patients treated at a single tertiary hospital in China., Methods: Risk factors of 379 consecutive surgically resected early gastric carcinoma (EGC) diagnosed according to the 2010 World Health Organization criteria were studied by reviewing their medical records and esophagogastroduodenoscopy/biopsy findings and interviewing patients and family members for the patients' history of environmental toxin exposure (ETE), dietary habits, family (FCH) and personal cancer history (PCH) and survival. Differences between PGC (n = 115), DGC (n = 264) and age-matched and gender-matched controls (n = 225) were compared., Results: Proportion of early PGC in all EGC patients was increased significantly (P < 0.05). The independent risk factors for both PGC and DGC identified by multivariate analysis were intake of preserved food and little fruit, and gastric mucosal intestinal metaplasia and atrophy (all P < 0.05). Advanced age (odds ratio [OR] 9.83, P < 0.01), PCH (OR 5.09, P < 0.05), a high body mass index (>24 kg/m(2) ) (OR 2.79, P < 0.01) and ETE (OR 2.31, P < 0.05) were independent risk factors for PGC, but not male gender, tobacco or alcohol abuse, hiatus hernia, gastroesophageal reflux disease or columnar-lined esophagus. In contrast, FCH (OR 2.34, P < 0.01) and Helicobacter pylori infection (OR 2.81, P < 0.001) were independent risk factors for DGC., Conclusion: Independent risk factors for PGC in Chinese patients differ from those of DGC or esophageal adenocarcinoma, supporting the classification of PGC as a separate gastric carcinoma entity in the Chinese populations., (© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Objective: Guided by the recently established histological criteria of the gastroesophageal junction (GEJ), we aimed to investigate and compare trends in the proportions of small (≤ 2 cm) proximal gastric carcinoma (PGC) vs non-PGC (NPGC) in Chinese patients over an 8-year period., Methods: The study was conducted with consecutive surgical resected specimens of small PGC that was located within 3 cm below the GEJ and NPGC (located at all other gastric regions) treated at a single medical center in China. Differences in proportions between the two groups were compared., Results: Among all 313 cases, 111 (35.5%) were classified as PGC and the remaining 202 (64.5%) as NPGC. Patients with PGC were significantly elder than those with NPGC, and none aged younger than 40 years. The proportions of PGC significantly and progressively increased from 16% in 2004 to 45% in 2011, in contrast to a steady decreasing trend for NPGC from 84% to 55% over the same period. The difference in trends between the two groups approached, but was not at a statistically significant level (P = 0.08). Proportions of small cancers in the gastric corpus and in female patients remained low and stable, in contrast to a significantly higher proportion in male patients (P < 0.05)., Conclusions: Our data showed a significantly upward-shifting trend in the proportions of small PGC, primarily in elderly male patients, in contrast to a downward shifting trend in NPGC over the most recent 8-year period in Chinese patients., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background and Aim: In this retrospective study, we investigated the safety and efficacy of endoscopic excavation of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer., Materials and Methods: Between November 2007 and June 2012, 212 patients with gastric SETs originating from the MP layer were treated via endoscopic excavation. The key procedures were: (1) injecting a mixture solution (100 mL saline+2 mL indigo carmine+1 mL epinephrine) into the submucosa around the tumor; (2) making a cross-incision of the mucosa and then excavating the tumor by the technique of endoscopic excavation. After the tumor was completely excavated from the MP layer, it was removed using a snare; (3) closing the artificial ulcer with clips., Results: The mean diameter of the 212 tumors was 16.5 mm. Complete resection by endoscopic excavation was achieved in 204 cases (96.2%). The rate of complete resection was significantly higher for tumors <2 cm (98.0%) than for tumors >2 cm (91.9%) (P=0.035). Perforation occurred in 32 cases (15.1%), and massive bleeding occurred in 9 cases (4.2%) during the procedure. The rate of perforation was significantly higher for the fundus and the body than for antrum (21.5%, 11.5%, 0%, respectively; P=0.036), and also differed significantly in relation to histologic diagnosis (23.7% for gastrointestinal stromal tumors vs. 7.8% for leiomyoma; P=0.001). Histologic diagnosis showed that the density of gastrointestinal stromal tumors located in the fundus and the body of the stomach was significantly higher than in the antrum (44.1%, 51.9%, 13.3%, respectively; P=0.036)., Conclusions: Endoscopic excavation is a safe and efficient method for resecting small (>3.5 cm) gastric SETs originating from the MP layer.

Background: The benefit of adjuvant treatment in gastric adenocarcinoma was demonstrated by randomized, controlled trials of patients with locally advanced tumors. Thus, its role for stage IIB-IIIC disease is widely accepted. We aimed to identify patients with stage IA-IIA gastric adenocarcinoma who have a poor prognosis and thus may benefit from adjuvant treatment., Methods: Patients with gastric adenocarcinoma who underwent surgical resection with pathological evaluation of ≥15 lymph nodes and had available disease-specific survival (DSS) data were identified from the Surveillance Epidemiology and End Results Registry. Survival differences were evaluated with the log-rank test and Cox multivariate analysis., Results: Stage and TN grouping strongly predicted DSS (P < 0.001, P < 0.001). Stage IA tumors had an excellent outcome: 91 ± 1.2 % 5-year DSS. The TN groupings of stages IB and IIA had the next best outcomes with 5-year DSS from 66 ± 4.6 % to 81 ± 2.3 %. Older age (P < 0.001), higher grade (P = 0.004), larger tumor size (P < 0.001), and proximal tumor location (P < 0.001) were independent predictors of worse DSS in stage IB-IIA tumors. We devised a risk stratification scheme for stage IB-IIA tumors where 1 point was assigned for age >60 years, tumor size >5 cm, proximal tumor location, and grade other than well-differentiated. Five-year DSS was 100 % for patients with 0 points; 86 ± 4.3 %, 1 point; 76 ± 3 %, 2 points; 72 ± 2.8 %, 3 points; and 48 ± 4.9 %, 4 points (P < 0.001)., Conclusions: Patients with stage IB-IIA gastric adenocarcinoma and ≥2 adverse features (age >60 years, tumor size >5 cm, proximal location, and high-grade) have 5-year DSS ≤76 %. Adjuvant therapy may be warranted for these patients.

Aim: To investigate HER2 expression and its correlation with clinicopathological variables between proximal and distal gastric cancers (GC) in the Chinese population., Methods: Immunostaining of HER2 was performed and scored on a scale of 0-3 in 957 consecutive GC cases, according to the revised scoring criteria of HercepTest(TM) as used in the ToGA trial. Correlations between HER2 expression and clinicopathologic variables of proximal (n = 513) and distal (n = 444) GC were investigated., Results: Our results showed that HER2 expression was significantly higher in the proximal than in distal GC (P < 0.05). Overall, HER2 expression was significantly higher in male patients (P < 0.01), the Lauren intestinal type (P < 0.001), low-grade (P < 0.001) and pM1 (P < 0.01) diseases, respectively. There was a significant difference in HER2 expression among some pTNM stages (P < 0.05). In contrast, HER2 expression in the distal GC was significantly higher in male patients (P < 0.001), low-grade histology (P < 0.001), the Lauren intestinal type (P < 0.001), and pM1 (P < 0.001). In the proximal GC, however, higher HER2 expression scores were observed only in tumors with low-grade histology (P < 0.001) and the Lauren intestinal type (P < 0.001)., Conclusion: HER2 over-expression in GC of Chinese patients was significantly more common in proximal than in distal GC, and significantly correlated with the Lauren intestinal type and low-grade histology in both proximal and distal GC, and with pM1 disease and male gender in distal GC.

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., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Carcinoma of the gastroesophageal junction (GEJ) is defined as carcinoma that crosses the GEJ line, irrespective of where the tumor epicenter is located. This group of cancer is rare but controversial. Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries, this cancer is believed to arise from Barrett's esophagus (BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology, clinicopathology, and molecular pathobiology in relation to BE. As such, the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma (EA). This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients. The emerging evidence derived from those studies suggests: (1) both BE and EA are uncommon in the Chinese population; (2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer, not those of EA; (3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively; and (4) prognostic factors of GEJ cancer in Chinese are similar, but not identical, to those of EA. In conclusion, the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA. Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.

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.

The aim of this study was to systematically investigate clinicopathologic features of the recently described pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus (n = 43). Patient median age was 66 years (range, 51-90 years). The male-to-female ratio was 7.6. Grossly, pancreatic acinar-like adenocarcinoma tumors were nonencapsulated with the median size of 5.5 cm (range, 2-10.5). Bormann's types 1 to 4 tumors were in 7%, 9%, 67%, and 16% cases, respectively. Frank necrosis, hemorrhage, and cysts were rare or absent. Lymphovascular (81%), perineural (74%), and lymph node (81%) invasions were more common in the pancreatic acinar-like adenocarcinoma than in the non-pancreatic acinar-like adenocarcinoma (n = 94) groups. Microscopically, pancreatic acinar-like adenocarcinoma tumors showed acinar (78%), micropapillary (12%), microcystic, solid, trabecular, and mixed neuroendocrine or signet ring (33%) patterns of growth. No adenosquamous differentiation was noted in the pancreatic acinar-like adenocarcinoma group. Nuclei were round to oval with thickened nuclear membrane, stippled chromatin, and single prominent nucleoli. Mitotic figures were variable. The cytoplasm was moderate, eosinophilic, finely granular, and diffusely immunoreactive to the α1-chymotrypsin antibody in all cases to various degrees. Tumor stroma was nondesmoplastic, delicate, and fibrovascular. Pancreatic acinar-like adenocarcinoma tumors staged pI, pII, pIII, and pIV were in 2%, 21%, 70%, and 7% of cases, respectively. The median number of follow-up months after surgery was 29. The 2-year survival rate was 67%, lower than that (73%) in the non-pancreatic acinar-like adenocarcinoma group. A worse overall survival trend was found for patients in the pancreatic acinar-like adenocarcinoma than in non-pancreatic acinar-like adenocarcinoma groups, but the difference was not statistically significant. Age older than 75 years and overall pathology stage were independent risk factors., (Published by Elsevier Inc.)

SIRT1 is a deacetylase that modifies gene expression. Some researchers have found that SIRT1 is upregulated in malignant tumor tissues. Therefore, this study investigated the SIRT1 expression in gastric cardiac carcinoma and its correlation with clinicopathologic features and prognosis. Tissue microarray technique and immunohistochemical stains were used to detect the expression of SIRT1, p53, and Ki-67 in 176 gastric cardiac carcinoma tissues and 32 normal gastric cardiac region tissues. SIRT1 expression in gastric cardiac carcinoma was significantly higher than that in normal gastric cardiac tissues and was associated with lymphatic metastasis, TNM stage, survival rate and mean survival time. Expression of Ki-67 in the SIRT1 positive group was significantly higher than that in the negative group. In conclusion, high expression of SIRT1 in gastric cardiac carcinoma was correlated with lymphatic metastasis, TNM stage, proliferative status and prognosis. SIRT1 might be a biological parameter to evaluate malignant degree and prognosis of gastric cardiac carcinoma.

Background: Radical resection with regional lymphadenectomy is recommended for all sporadic gastric carcinoids. Local resection, however, is accepted for some carcinoids from other gastrointestinal sites (i.e., appendix and rectum). We sought to examine the relation of tumor size and depth to lymph node metastasis to determine whether gastric carcinoids can be selected for endoscopic resection. We also sought to quantify the utilization of lymph node sampling., Methods: 984 patients with localized gastric carcinoids who underwent cancer-directed surgery between 1983 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry database., Results: Tumor size and depth predicted probability of lymph node metastasis. Lymph node metastasis was not seen in intraepithelial (IE) tumors <2 cm. Of tumors <1 cm invading into the lamina propria or submucosa (LP/SM), 3.4% had lymph node metastasis. Excluding IE tumors <2 cm and LP/SM tumors <1 cm, all other subgroups based on size and depth had rates of lymph node metastasis ≥ 8%. Tumor size and depth predicted probability of lymph node sampling. Overall, only 21% of tumors had lymph node sampling. Excluding IE tumors <2 cm and LP/SM tumors <1 cm, only 43% of tumors had lymph node sampling., Conclusions: Tumor size and depth predict lymph node metastasis for gastric carcinoids. Endoscopic resection may be appropriate for intraepithelial (IE) tumors <2 cm and perhaps tumors <1 cm invading into the lamina propria or submucosa. Lymph node sampling is underused for gastric carcinoids at high risk for lymph node metastasis.

Aims: To compare the clinical and pathological features of gastro-oesophageal junction (GEJ) carcinomas in Chinese and American patients., Methods and Results: Eighty consecutive patients with a GEJ carcinoma (43 from mainland China, and 37 from the USA) were evaluated for association with Barrett oesophagus (BO), chronic Helicobacter pylori gastritis, intestinal metaplasia, and outcome. GEJ carcinomas were defined as tumours that were located within 20 mm of, and crossed, the GEJ. Overall, GEJ carcinomas from Chinese patients revealed significantly more frequent location in the proximal stomach, higher pathological stage, larger size, younger patient age, and association with chronic H. pylori gastritis. In contrast, GEJ cancers from American patients showed a strong association with distal oesophageal location, BO, and associated intestinal metaplasia and dysplasia. Pathologically, GEJ carcinomas from American patients were predominantly adenocarcinomas, whereas Chinese patients showed a higher proportion of mucinous, adenosquamous, acinar or neuroendocrine tumours. Overall, 3- and 5-year survival rates were statistically similar between both patient groups, but upon multivariate analysis, Chinese patients showed statistically better survival rates for stage III tumours., Conclusions: Most GEJ carcinomas in patients from China represent proximal gastric cancers associated with chronic H. pylori gastritis, and BO-associated carcinomas are rare among this patient population., (© 2011 Blackwell Publishing Limited.)

The aim of this study was to compare the 7th with the 6th edition of the American Joint Commission on Cancer Staging System for prognostic stratification of gastric cardiac carcinomas involving the esophagus. We retrospectively compared differences in pathological stages with patient survival between the 7th and the 6th staging systems in 142 consecutive resection cases of this cancer. Patient median age was 65 years. The male-female ratio was 3.3. The epicenter of all tumors was within 5 cm below the gastroesophageal junction. The median tumor size was 5.0 cm. Most tumors (79%) were typical adenocarcinomas and the rest showed uncommon histology types. Using the guidelines for gastric cancer, this group of cancer was better stratified by the 7th than the 6th edition of the staging system, especially for pathological nodal (pN) and overall stage pIIIC. Patients with celiac axis nodal disease had the 5-year survival rate worse than those staged at pN3A and pIIIA. Patients staged at pT3 and pN3B had the 5-year survival rate worse than those at pM1 and pIV. We showed that the overall stage of gastric cardiac carcinomas was better stratified by gastric than by esophageal cancer grouping. We conclude that these tumors are better stratified with the 7th than the 6th edition of the gastric staging system, especially for pIII cancers, and better staged by the new gastric than esophageal cancer staging system. We propose that the staging of these tumors be reverted to gastric grouping and combine pT3 and pN3B into the overall stage pIV.

Aberrant hypermethylation of CpG islands in the promoter region of tumor suppressor and other important genes in neoplastic cells of lymphoma has been demonstrated to be one of the mechanisms for epigenetic loss of gene function. In this study, we analyzed promoter hypermethylation of the following genes in 49 cases of primary gastric lymphoma (PGL): ATM, p16INK4a(CDKN2A), hMLH1, MGMT, DAPK, and CDH1(ECAD). The PGL cases studied included 26 (53%) cases of diffuse large B-cell lymphoma (DLBCL), 12 (25%) cases of extranodal marginal zone lymphoma (MZL), 7 (14%) cases of MZL with large cell transformation (MZL/DLBCL), 1 (2%) case of follicular lymphoma (FL), one (2%) case of Burkitt-like lymphoma (BL), one case (2%) of lymphoplasmacytic lymphoma (LPL) and one case (2%) of peripheral T-cell lymphoma. Available pathologic data regarding to extragastric involvement at the time of resection of the PGLs were reviewed and correlated. Promoter hypermethylation was detected in 6 of 49 (12.2%) cases for ATM; 13 of 49 (26.5%) for p16INK4a, 19 of 49 (38.8%) for hMLH1; 22 of 49 (44.9%) for MGMT; 27 of 49 (55.1%) for DAPK and 16 of 49 (32.7%) for CDH1. A total of 85% of the PGLs had promoter hypermethylation in at least one of these genes. With different histologic subtypes, promoter hypermethylation of DAPK, hMLH1, and CDH1 genes occurred in 70%, 42%, and 42% respectively for DLBCL, which appeared to be higher than combined MZL and MZL/DLBCL subgroup. Approximately 81% PGLs demonstrated H. pylori infection by immunohistochemistry. H. pylori status did not appear to be statistically correlated with promoter hypermethylation of the genes. Of 37 PGL cases, 19 cases had extragastric involvement at the time of resection, indicating relatively higher stage disease. The frequencies of promoter methylation in those cases were 58% for DAPK, 42% for hMLH1, 37% for CDH1, 26% for p16INK4a and 11% for ATM respectively. The promoter methylation at MGMT gene was significantly higher in the PGLs without extragastric involvement (61%) as compared to those with extragastric involvement (26%).

Carcinomas involving the gastroesophageal junction are common in China. The histopathologic characteristics of these cancers have not been systematically investigated. Reported are 41 such resected cancers from Chinese patients (30 men, 11 women). Their mean age was 62 years. The mean tumor size was 4.4 cm (range, 2 to 9 cm), and 58% were poorly differentiated. An unusual spectrum of tumor differentiation was observed, including adenocarcinomas (83%), adenosquamous (32%), colloid (2%), signet-ring (10%), squamous (5%), oncocytic (7%), pancreatic acinar (12%), and neuroendocrine (5%) carcinomas. Cancers with multiple types of differentiation in the same tumor were identified in 37 cases (90%). The adjacent gastric cardiac mucosa showed hyperplasia, oncocytic, and pancreatic acinar metaplasia, and mild chronic inflammation. Dysplasia was uncommon (n = 6). Barrett esophagus was not identified. Carcinomas involving the gastroesophageal junction in the Chinese are morphologically distinct, heterogeneous, and may be of esophageal origin.

The p16 (CDKN2a/INK4a) gene is an important tumor-suppressor gene, involved in the p16/cyclin-dependent kinase/retinoblastoma gene pathway of cell cycle control. The p16 protein is considered to be a negative regulator of the pathway. Promoter hypermethylation resulting in inactivation of the p16 gene has been found in various hematopoietic malignancies, including non-Hodgkin's lymphoma, and may play a role in transformation/clinical aggressiveness of those tumors. However, the p16 protein expression in primary gastric lymphoma has not been studied. In this study, we characterize protein expression and promoter hypermethylation of the p16 gene in B-cell primary gastric lymphomas from China. In all, 43 cases of B-cell primary gastric lymphoma were investigated. They consisted of 24 (56%) cases of diffuse large-cell lymphoma, 12 (28%) cases of extranodal marginal zone lymphoma, six (14%) cases of extranodal marginal zone lymphoma with large-cell transformation and one (2%) case of follicular lymphoma. Loss of p16 protein expression was found in 34 (79%) out of 43 cases, while the remaining nine (21%) cases showed positivities for the p16 protein. All 43 cases were further characterized by methylation-specific polymerase chain reaction (PCR) to analyze p16 promoter hypermethylation status. In total, 11 (26%) of 43 cases were positive for p16 promoter hypermethylation. Among those, 10 (30%) out of the 33 cases negative for the p16 immunostaining showed promoter hypermethylation, whereas only one (10%) out of the 10 cases that were positive for the p16 immunostaining displayed promoter hypermethylation. Of the 43 cases, 30 had limited pathologic data at the time of resection. Primary gastric lymphoma involved extragastric sites (lymph node or liver) in 17 (57%) of 30 cases, while the remaining 13 (43%) cases were only limited to the stomach. Loss of p16 protein expression was found in 14 (82%) of 17 cases with extragastric involvement and in 11 (85%) of 13 cases without such involvement. In conclusion, loss of p16 protein expression is frequent in those B-cell primary gastric lymphomas and approximately one-third of such loss correlated with promoter hypermethylation. Despite limited pathologic data, loss of p16 protein expression appears not to be correlated with extragastric involvements.

Objective Guided by the recently established histological criteria of the gastroesophageal junction ( GEJ), we aimed to investigate and compare trends in the proportions of small (≤2 cm) proximal gastric carcinoma ( PGC) vs non- PGC ( NPGC) in Chinese patients over an 8-year period. Methods The study was conducted with consecutive surgical resected specimens of small PGC that was located within 3 cm below the GEJ and NPGC (located at all other gastric regions) treated at a single medical center in China. Differences in proportions between the two groups were compared. Results Among all 313 cases, 111 (35.5%) were classified as PGC and the remaining 202 (64.5%) as NPGC. Patients with PGC were significantly elder than those with NPGC, and none aged younger than 40 years. The proportions of PGC significantly and progressively increased from 16% in 2004 to 45% in 2011, in contrast to a steady decreasing trend for NPGC from 84% to 55% over the same period. The difference in trends between the two groups approached, but was not at a statistically significant level ( P = 0.08). Proportions of small cancers in the gastric corpus and in female patients remained low and stable, in contrast to a significantly higher proportion in male patients ( P < 0.05). Conclusions Our data showed a significantly upward-shifting trend in the proportions of small PGC, primarily in elderly male patients, in contrast to a downward shifting trend in NPGC over the most recent 8-year period in Chinese patients. [ABSTRACT FROM AUTHOR]