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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies. [ABSTRACT FROM AUTHOR]

Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and comparative review of each country’s guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations. [ABSTRACT FROM AUTHOR]

Purpose: Recently, non-exposure simple suturing endoscopic full-thickness resection (NESS-EFTR) was developed to prevent tumor exposure to the peritoneal cavity. This study aimed to evaluate the feasibility of NESS-EFTR with sentinel basin dissection for early gastric cancer (EGC). Materials and Methods: This was the prospective SENORITA 3 pilot. From July 2017 to January 2018, 20 patients with EGC smaller than 3 cm without an absolute indication for endoscopic submucosal dissection were enrolled. The sentinel basin was detected using Tc99m-phytate and indocyanine green, and the NESS-EFTR procedure was performed when all sentinel basin nodes were tumor-free on frozen pathologic examination. We evaluated the complete resection and intraoperative perforation rates as well as the incidence of postoperative complications. Results: Among the 20 enrolled patients, one dropped out due to large tumor size, while another underwent conventional laparoscopic gastrectomy due to metastatic sentinel lymph nodes. All NESS-EFTR procedures were performed in 17 of the 18 other patients (94.4%) without conversion, and the complete resection rate was 83.3% (15/18). The intraoperative perforation rate was 27.8% (5/18), and endoscopic clipping or laparoscopic suturing or stapling was performed at the perforation site. There was one case of postoperative complications treated with endoscopic clipping; the others were discharged without any event. Conclusions: NESS-EFTR with sentinel basin dissection is a technically challenging procedure that obtains safe margins, prevents intraoperative perforation, and may be a treatment option for EGC after additional experience. [ABSTRACT FROM AUTHOR]

Purpose: The guidelines for pathological evaluation of early gastric cancer (EGC) recommend wider section intervals for surgical specimens (5-7 mm) than those for endoscopically resected specimens (2-3 mm). Studies in surgically resected EGC specimens showed not negligible lymph node metastasis risks in EGCs meeting the expanded criteria for endoscopic submucosal dissection (ESD). Materials and Methods: This retrospective study included 401 EGC lesions with an endoscopic size of ≤ 30 mm detected in 386 patients. Pathological specimens obtained by ESD or surgery were cut into 2-mm section intervals for reference. Submucosal or lymphovascular invasion (LVI) was evaluated arbitrarily in 4- or 6-mm section intervals. McNemar's tests compared the differences between submucosal and LVI. Results: Submucosal invasion was detected in 29.2% (117/401) and LVI in 9.5% (38/401) at 2-mm interval. The submucosal invasion detection rates in 4-mm intervals decreased to 88.0% or 90.6% (both P<0.001), while the LVI detection rates decreased to 86.8% or 57.9% (P=0.025 and P<0.001, respectively). In 6-mm intervals, the submucosal and LVI detection rates decreased further to 72.7-80.3% (P<0.001 for all three sets) and 55.3-63.2% (P<0.001 for all three sets), respectively. Among 150 out-of-indication cases at 2-mm interval, 4-10 (2.7%-6.7%) at 4-mm intervals, and 10-17 (6.7%-11.3%) at 6-mm intervals were misclassified as lesions meeting the curative resection criteria due to the underestimation of submucosal or LVI. Conclusions: After ESD, the 2-mm wide section interval was suitable for the pathological evaluation of focal submucosal or LVI. Thus, if an EGC lesion meets the expanded criteria for the ESD specimen pathological evaluation, it could be safely followed up. [ABSTRACT FROM AUTHOR]

Purpose The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. Materials and Methods We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. Results The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. Conclusion The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia. [ABSTRACT FROM AUTHOR]

Undifferentiated-type carcinoma has a high incidence of lymph node metastasis. The independent risk factors for lymph node metastasis in undifferentiated-type carcinoma are invasion depth, tumor size, lymphovascular invasion, and presence of ulcer. In the cases that meet the curative resection criteria, no lymph node metastasis was observed in the Japanese studies, but some metastases were observed in Korean studies. After performing curative endoscopic submucosal dissection, the survival rate is similar to that of gastrectomy. The discrepancy between endoscopy and pathology is high in undifferentiated-type carcinoma. The tumor size in endoscopy is a significant risk factor for non-curative resection, and when the tumor size is small, the non-curative resection rate is significantly reduced. Lymphovascular invasion can be assessed in pathologic examination and D2-40 stain is helpful. The presence of ulcer should be determined by pathology, but ulcer's omission in pathology report makes the analysis difficult. Undifferentiated-type carcinomas with differentiated-type components show higher lymph node metastasis rate than that of pure undifferentiated-type carcinomas. The lymph node metastasis rate of signet ring cell type is lower than that of other undifferentiated-type carcinomas and is similar to differentiated-type carcinomas. The application of these additional histologic findings may improve the indication of endoscopic submucosal dissection. [ABSTRACT FROM AUTHOR]

Background/Aims: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. [ABSTRACT FROM AUTHOR]

Purpose: Negative Helicobacter pylori status has been identified as a poor prognostic factor for survival in gastric cancer (GC) patients who underwent surgery. The aim of this study was to examine the effect of H. pylori eradication on long-term outcomes after distal gastrectomy for GC. Materials and Methods: We analyzed the survival of 169 distal GC patients enrolled in a prospective randomized trial evaluating histologic changes of gastric mucosa after H. pylori eradication in the remnant stomach. The outcomes measured were overall survival (OS) and GC recurrence rates. Results: The median follow-up duration was 9.4 years. In the modified intention-to-treat analysis including patients who underwent H. pylori treatment (n=87) or placebo (n=82), 5-year OS rates were 98.9% in the treatment group and 91.5% in the placebo group, and Kaplan- Meier analysis showed no significant difference in OS (p=0.957) between groups. In multivariate analysis, no difference in overall mortality was observed between groups (adjusted hazard ratio [aHR] for H. pylori treatment, 0.75; p=0.495) or H. pylori-eradicated status (aHR for positive H. pylori status, 1.16; p=0.715), while old age, male sex, and advanced stage ! IIIa were independent risk factors. Six patients in the treatment group (6.9%) and seven patients in the placebo group (8.5%) had GC recurrences, and GC recurrence rates were not different according to H. pylori treatment (5-year GC recurrence rates, 4.6% in the treatment group vs. 8.5% in the placebo group; p=0.652). Conclusion: H. pylori eradication for GC patients who underwent distal gastrectomy did not compromise long-term survival after surgery. [ABSTRACT FROM AUTHOR]

Purpose: Early gastric cancer cases that are estimated to meet indications for treatment before endoscopic submucosal resection are often revealed to be out-of-indication after the treatment. We investigated the short-term treatment outcomes in patients with early gastric cancer according to the pretreatment clinical endoscopic submucosal resection indications. Materials and Methods: We retrospectively reviewed the medical records of patients with early gastric cancer that met the pretreatment endoscopic submucosal resection indications, from 2004 to 2011. Curative resection rate and proportion of out-of-indication cases were compared according to the pre-endoscopic submucosal resection indications. Pre-endoscopic submucosal resection factors associatedwith out-of-indication in the final pathological examination were analyzed. Results: Of 756 cases, 660 had absolute and 96 had expanded pre-endoscopic submucosal resection indications. The curative resection rate was significantly lower in the patients with expanded indications (64.6%) than in those with absolute indications (81.7%; P<0.001). The cases with expanded indications (30.2%) were revealed to be out-of-indication more frequently than the cases with absolute indications (13.8%; P<0.001). Age of >65 years, tumor size of >2 cm, tumor location in the upper-third segment of the stomach, and undifferentiated histological type in pre-endoscopic submucosal resection evaluations were significant risk factors for out-of-indication after endoscopic submucosal resection. Conclusions: Non-curative resection due to out-of-indication occurred in approximately one-third of the early gastric cancer cases that clinically met the expanded indications before endoscopic submucosal resection. The possibility of additional surgery should be emphasized for patients with early gastric cancers that clinically meet the expanded indications. [ABSTRACT FROM AUTHOR]

Background: Worldwide, gastric cancer (GC) is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects. Objective: To determine oncogenic mechanisms and novel therapeutic targets specific for GC by identifying commonly dysregulated genes from the tumours of both Asian-Pacific and Caucasian patients. Methods: We generated transcriptomic profiles of 22 Caucasian GC tumours and their matched non-cancerous samples and performed an integrative analysis across different GC gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signalling pathways by RNAi and/or pharmacological inhibition. Results: Hepatocyte nuclear factor-4a (HNF4a) upregulation was a key signalling event in gastric tumours from both Caucasian and Asian patients, and HNF4a antagonism was antineoplastic. Perturbation experiments in GC tumour cell lines and xenograft models further demonstrated that HNF4a is downregulated by AMPKa signalling and the AMPK agonist metformin; blockade of HNF4a activity resulted in cyclin downregulation, cell cycle arrest and tumour growth inhibition. HNF4a also regulated WNT signalling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumours. Conclusions: Our results indicate that HNF4a is a targetable oncoprotein in GC, is regulated by AMPK signalling through AMPKa and resides upstream of WNT signalling. HNF4a may regulate 'metabolic switch' characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKa-HNF4a-WNT5A signalling cascade represents a potentially targetable pathway for drug development. [ABSTRACT FROM AUTHOR]

Background/Aims: We evaluated the effectiveness of an endoscopic ultrasonography (EUS)-based treatment plan compared to an endoscopy-based treatment plan in selecting candidates with early gastric cancer (EGC) for endoscopic submucosal dissection based on the prediction of invasion depth. Methods: We reviewed 393 EGCs with differentiated histology from 380 patients who underwent EUS from July 2007 to April 2010. The effectiveness of the EUS-based and endoscopy-based plans was evaluated using a simplified hypothetical treatment algorithm. Results: The numbers of endoscopically determined mucosal, indeterminate, and submucosal cancers were 253 (64.4%), 56 (14.2%), and 84 (21.4%), respectively. Overall, the appropriate treatment selection rates were 75.3% (296/393) in the endoscopy-based plan and 71.5% (281/393) in the EUS-based plan (p=0.184). For endoscopic mucosal cancers, the appropriate treatment selection rates in the endoscopy-based plan were 88.1% (223/253), while the use of an EUS-based plan significantly decreased this rate to 81.4% (206/253) (p=0.036). For endoscopic submucosal cancers, the appropriate selection rates did not differ between the endoscopy-based plan (46.4%, 39/84) and the EUS-based plan (53.6%, 45/84) (p=0.070). Conclusions: EUS did not increase the likelihood of selecting the appropriate treatment in differentiated-type EGC. Therefore, EUS may not be necessary before treating differentiated-type EGC, especially in endoscopically presumed mucosal cancers. [ABSTRACT FROM AUTHOR]

Background and Aim: Current endoscopic full-thickness resection (EFTR) methods are limited by their transmural communication and exposure of tumor to the peritoneum. The aim of this study was to test the feasibility of a new resection technique that does not expose the mucosa to the peritoneum, although it involves an easy and secure suture method, which could be applied in the clinical setting.Methods: The nonexposure endolaparoscopic full-thickness resection with simple suturing technique was performed in four pigs. This new technique includes the steps of laparoscopic seromuscular suturing, which results in inversion of the stomach wall; EFTR of the inverted stomach wall from inside the stomach; and finally, endoscopic mucosal suturing with endoloops and clips.Results: En bloc and complete resections were achieved without adverse events in all pigs. The mean (± standard deviation) operation time was 137.0 ± 28.2 minutes. All pigs survived with no clinical evidence of illness until euthanasia. Gross and microscopic examination of the resection site showed healing without evidence of leakage or infection.Conclusion: The nonexposure endolaparoscopic full-thickness resection with simple suturing technique was feasible in an animal model. [ABSTRACT FROM AUTHOR]

Purpose Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylon-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population. Materials and Methods We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer. Results TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers. Conclusion The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors. [ABSTRACT FROM AUTHOR]

Purpose As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. Materials and Methods We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. Results Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. Conclusion The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET. [ABSTRACT FROM AUTHOR]

Objective: Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans. Methods: We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer. Results: The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17-51.06]) or the -592C (OR [95% CI] = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080). Conclusions: Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer. [ABSTRACT FROM AUTHOR]

Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus-predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) ( p = .001). In patients with a DU, moderate-severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46-9.36, and OR, 7.72; 95% CI, 3.18-18.7, respectively). Additionally, moderate-severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06-18.5, and OR, 9.25, 95% CI, 2.39-35.8, respectively). A DU is not rare in patients with GC in a high-risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development. [ABSTRACT FROM AUTHOR]

Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. We used the MethyLight assay to evaluate the methylation status of 16 CpG island loci that are hypermethylated in GC. We analyzed the relationship between CpG island hypermethylation of these 16 genes and the clinicopathological features in 191 advanced GCs. A significant difference was observed between the number of methylated genes in Epstein-Barr virus (EBV)-negative and microsatellite instability (MSI)-negative GCs of different histological types (Lauren classification; P < 0.01). We found that mixed-type (MT) carcinomas, which have both diffuse-type (DT) and intestinal-type (IT) components, had more methylated genes (10.6) than either DT carcinomas (7.6 methylated genes) or IT carcinomas (6.7 methylated genes) (P < 0.001). This trend was also observed when EBV-positive or MSI-positive GCs were excluded from the analysis (9.2, 6.9, and 4.8; P < 0.001). When the IT and DT components were dissected from MT carcinomas and the methylation of these 16 genes was evaluated, both components had a number of methylated genes similar to MT carcinomas, (10.2 and 9.7, respectively), which was significantly higher than was found in IT and DT carcinomas (P < 0.05). These findings indicate that MT carcinoma is distinct from IT and DT carcinomas in its enhanced CpG island hypermethylation status and implicate the enhanced promoter CpG island hypermethylation in the histogenesis of MT carcinoma. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) of tumor in the upper part of the stomach is technically difficult and has a high complication rate. We compared the feasibility and safety of ESD for metachronous tumor found in the remnant stomach after distal gastrectomy with ESD for tumor in the upper third of the intact stomach. We retrospectively compared clinical outcome and safety of 13 lesions (11 early gastric cancers (EGCs) and 2 dysplasias) in the remnant stomach and 30 lesions (28 EGCs and 2 dysplasias) in the upper third of the intact stomach. All patients were treated with ESD at a cancer center hospital. En bloc resection rates were 100% (13/13) for remnant gastric tumor and 87% (26/30) for upper-third tumor ( p = 0.30). En bloc resection rates with tumor-free margins (R0 resection) were 92% (12/13) for remnant gastric tumor and 73% (22/30) for upper-third tumor ( p = 0.24). Curative resection rates were 85% (11/13) for remnant gastric tumor and 67% (20/30) for upper-third tumor ( p = 0.29). Median procedure duration for ESD was 68 min (range 32–233 min) in the remnant stomach and 78 min (range 45–261 min) in the intact stomach ( p = 0.49). One case of perforation and one of delayed bleeding occurred in the upper-third tumor group, whereas none occurred in the remnant tumor group. Local recurrence was found in no patients in the remnant gastric tumor group but in one patient in the upper-third tumor group. ESD for metachronous remnant gastric tumor was feasible and safe in comparison with ESD for tumor in the upper third of the intact stomach. [ABSTRACT FROM AUTHOR]

We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients. Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA. Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS. Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori eradication is recommended in post-gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients. Materials and Methods: Consecutive patients (194) with gastric adenocarcinoma were prospectively enrolled. Helicobacter pylori was evaluated by serology, histology and rapid urease test. Biopsy sites included antrum lesser curvature, upper body lesser curvature (UBLC) and upper body greater curvature (UBGC). Two biopsy specimens were obtained from each site for histological examination. One additional specimen was obtained from UBGC for the rapid urease test. Results: The overall infection rate of H. pylori was 84.0% (95% CI 78.9–89.2). The sensitivity of histology for detecting H. pylori at various sites was: antrum (54.9%; 95% CI 45.7–63.9), UBLC (80.3%; 95% CI 72.2–87.0) and UBGC (95.1%; 95% CI 89.6–98.2). Specificities of all three biopsy sites were more than 95%. Sensitivity and specificity of the rapid urease test performed at UBGC were 96% and 100%, respectively. Sensitivities of histology decreased in correlation with increasing severity of atrophy and intestinal metaplasia (both P < 0.001 using the chi-square test for trend). The proportions of moderate to marked atrophy/intestinal metaplasia at UBGC (12.8%/14.7%) were significantly lower than those at antrum (50.0%/57.8%, P < 0.001 respectively) or UBLC (40.0%/48.9%, P < 0.001 respectively). Conclusions: The UBGC side is the most sensitive and specific biopsy site to detect H. pylori in gastric cancer patients due to less frequent atrophy and intestinal metaplasia than at the antrum or UBLC side. [ABSTRACT FROM AUTHOR]

Background and Aim: A submucosal injection of sodium hyaluronate is widely used for mucosal elevation in endoscopic mucosal resection (EMR) or endoscopic submucosal dissection procedures; however, the oncologic safety of sodium hyaluronate remains unknown. Hyaluronate is the main ligand for CD44 and this interaction was reported to promote tumor progression in in vitro or animal studies. This study aimed to evaluate the effects of sodium hyaluronate on tumor growth after EMR for gastrointestinal cancers. Methods: The study included 18 consecutive patients who underwent surgery for locally-recurrent or remnant gastrointestinal cancers after EMR from January 2001 to December 2006. The immunohistochemical expression levels of Ki-67, CD44, ErbB2, and epidermal growth factor receptor (EGFR) were evaluated in the primary tumor tissue and the recurrent tumor. The protein expression in recurrent or remnant lesions was also compared between the sodium hyaluronate group and non-sodium hyaluronate group. Results: Sodium hyaluronate was used in nine of 14 cases with EMR for gastric cancers and in one of four cases for colon cancers. The time to operation after EMR was 133 days (5–687 days). An analysis of the immunohistochemical expression levels between primary and recurrent or remnant tumors showed no significant differences in the expression levels of Ki-67, CD44, ErbB2, and EGFR with or without sodium hyaluronate. Conclusions: We found no evidence that sodium hyaluronate stimulates the growth of remnant tumors after EMR. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the staging accuracy and prognostic role of preoperative endoscopic ultrasound (EUS) and computed tomography (CT) in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy. Results show that restaging by EUS and CT after neoadjuvant chemotherapy in patients with LAGC was found to be inaccurate, but suggests that downstaging by EUS is a useful clinical parameter to predict a better outcome for LAGC patients.

OBJECTIVES: Helicobacter pylori ( H. pylori) eradication is strongly recommended for gastric cancer patients who undergo subtotal gastrectomy. The efficacy of proton pump inhibitor-based triple therapy for H. pylori eradication has not been adequately assessed in the gastric remnant. The aim of this study was to compare the efficacy of postoperative versus preoperative H. pylori eradication therapy. METHODS: A total of 138 distal gastric cancer patients with H. pylori infection were randomized to receive either preoperative (preop, N = 68) or postoperative (postop, N = 70) proton pump inhibitor-based triple therapy for H. pylori eradication. The regimen consisted of rabeprazole 10 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. Eradication was assessed by rapid urease test and histology 12 wk after surgery. RESULTS: By intention-to-treat (ITT) analysis, H. pylori eradication rates were 84.6% (95% CI 73.5–92.4) in the preop group and 83.1% (95% CI 71.7–91.2) in the postop group ( P= 0.99). By per protocol (PP) analysis, the rates were 87.3% (95% CI 76.5–94.4) in the preop group and 86.9% (95% CI 75.8–94.2) in the postop group ( P= 0.99). In the postop group, eradication rates did not differ with reconstruction method (Billroth I vs II, 80.4%[95% CI 66.1–90.6] vs 89.5%[95% CI 66.9–98.7] by ITT analysis ( P= 0.49), and 85.7%[95% CI 71.5–94.6] vs 89.5% (95% CI 66.9–98.7) by PP analysis, P= 0.99). CONCLUSIONS: In distal gastric cancer patients, the effect of proton pump inhibitor-based triple therapy for H. pylori eradication was not different whether given postoperatively or preoperatively. [ABSTRACT FROM AUTHOR]

We have previously reported the identification of a unique thymocyte-specific surface molecule, JL1, which was detected using the monoclonal antibody (mAb), anti-JL1. Interestingly, JL1 was shown to be expressed in most leukemias, irrespective of their immunophenotype, and subpopulations of normal bone marrow (BM) mononuclear cells (MNCs). Here we investigated the potential usefulness of the anti-JL1 mAb as a therapeutic tool for leukemia. We demonstrated that the proliferation of cultured human leukemia cells was dramatically inhibited in vitro by anti-JL1 mAb conjugated with the polypeptide toxin, gelonin, but not by gelonin alone. We then systematically investigated the reactivity of the anti-JL1 mAb against normal human tissues to evaluate possible side effects along with various hematopoietic and nonhematopoietic tumor cell lines. All of 33 types of normal tissues except thymus and subpopulation of BM MNCs were clearly devoid of JL1 expression. Among tumor cell lines, all the nonhematopoietic cell lines tested were negative for JL1 expression, while some hematopoietic cell lines contained JL1 antigen. Collectively, the results showed the cytotoxic effects of anti-JL1-based immunotoxin against JL1-positive leukemic cells, sparing most normal tissues other than thymocytes and some BM MNCs. Therefore, we strongly suggest that gelonin-conjugated anti-JL1 mAb immunotoxin could be developed as a potential immunotherapeutic agent in the treatment of various types of JL1-positive acute leukemias. [ABSTRACT FROM AUTHOR]

Background/Aims Gastric carcinomas (GCs) can be divided into intestinal and diffuse types according to Lauren classification. Those types are associated with different clinical, histopathological, and molecular characteristics which suggests different pathogenesis. Previous studies revealed different expression of receptors, cell adhesion molecules, apoptosis- related proteins, all of which are part of signaling molecules. However, these signaling components do not act independently, but all of them are interlinked inside large-scale signaling network. Methods In order to consider this aspect, we investigated the difference between intestinal type- and diffuse type GC from the perspective of large-scale signaling network through the mathematical modeling and simulation analysis based on RNA sequencing data. Results As a result, six signaling components were consistently found as differentially activated components in three different expression profiles (i.e., TCGA, GSE62254, and GSE26253). Specifically, BIRC5, TTK, FHL1 were activated in intestinal type GCs while NEK2, NR2F1, FBLN5 were activated in diffuse type GCs. Among them, BIRC5 was validated as a marker of intestinal type GC in TMA analysis using tumor tissues of patients with GCs. Conclusions This study might provide a novel insight regarding the pathogenesis of GC with respect to signaling network. [ABSTRACT FROM AUTHOR]

Background/Aims Prospective cohort studies have reported that operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging systems could predict the risk of gastric epithelial neoplasia progression in patients without gastric cancer. We evaluated metachronous gastric neoplasia risk after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) patients without Helicobacter pylori infection according to the OLGA and OLGIM stages. Methods This retrospective study included 568 EGC patients who underwent ESD for EGC between 2004 and 2015. OLGA and OLGIM stages were determined when H. pylori status was all negative at biopsy specimens from the antrum, corpus lesser and greater curvature. OLGA and OLGIM stages III-IV was defined as high-risk group. Primary outcome was risk of metachronous gastric neoplasia including adenoma and cancer, and age-sex adjusted hazard ratio (aHR) was calculated using the Cox-proportional hazard model. Results During a median follow-up of 5.0 years, metachronous neoplasia developed in 71 of the 568 patients (12.5%; 42 cancer and 29 adenoma). Of 519 patients evaluated by OLGA stage, aHR for metachronous neoplasia was 6.81 in stage I, 4.71 in stage II, 7.68 in stage III, and 8.71 in stage IV. High-risk OLGA group (aHR, 1.82; p=0.028) had a significantly increased risk of metachronous neoplasia compared with low-risk group. OLGIM stages were evaluated in all included 568 patients, and risk of metachronous neoplasia increased with advanced OLGIM stages: aHR 2.25 in stage I, 2.56 in stage II, 3.35 in stage III, and 4.36 in stage IV. High-risk OLGIM group had also significantly increased metachronous neoplasia risk (aHR, 1.81; p=0.026). Conclusions OLGA and OLGIM stages may be a risk assessment tool for the prediction of metachronous gastric neoplasia development after ESD in EGC patients who had negative H. pylori infection. [ABSTRACT FROM AUTHOR]