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Adenosquamous carcinoma (ASC) is characterized as a mixed neoplasia (adenocarcinoma with glandular architecture and squamous cell carcinoma [SqCC]). Because most ASCs are found in the advanced stage at the time of diagnosis, early gastric ASC is an extremely rare tumor. Here, we present the case of an incidental finding of early gastric ASC in a 61-year-old Korean man during a health screening. Histological biopsy through esophagogastroduodenoscopy revealed a moderately differentiated adenocarcinoma in the distal body. The patient underwent endoscopic submucosal dissection and was diagnosed with ASC. The SqCC components of this tumor were located adjacent to the adenocarcinoma components and occupied 40% of the tumor. Two individual tumor components had invaded into the submucosal layer with lymphovascular invasion. An abdominal computed tomography scan indicated no definite mass or wall thickening of the stomach and revealed neither lymph node enlargement nor distant metastasis. To the best of our knowledge, this is the 14th reported case of early gastric ASC, and all cases were reported in East Asians. [ABSTRACT FROM AUTHOR]

Abstract: A three-dimensional (3D) culture of cancer cells has long been advocated as a better model of the malignant phenotype that is most closely related to tumorigenicity in vivo. To investigate the sensitivity of cancer cells to anticancer drugs, nanofiber scaffolds composed of PHBV and collagen peptide were fabricated by electrospinning. A 3D culture of cancer cells was successfully achieved by the use of nanofiber scaffolds. From the result of a chemosensitivity test, it was found that higher concentrations of anticancer drugs were required to achieve a comparable cytotoxic effect in 3D culture due to their structural architecture. These data demonstrate that the electrospun nanofiber scaffolds can provide a 3D model particularly appropriate for investigating mechanisms involved in cancer cell sensitivity to anticancer drugs. [Copyright &y& Elsevier]

Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and clinicopathological characteristics of EBVaGC according to the histological pattern. We retrospectively collected 18 specimens of surgically resected EBVaGCs. Whole-exome sequencing was performed for all cases. Moreover, PD-L1 expression and tumor-infiltrating lymphocyte (TIL) percentage were investigated. Among 18 EBVaGCs, 10 cases were of intestinal histology, 3 were of poorly cohesive histology, and the remaining 5 were of gastric carcinoma with lymphoid stroma histology. Whole-exome sequencing revealed that EBVaGCs with intestinal histology harbored pathogenic mutations known to frequently occur in tubular or papillary adenocarcinoma, including TP53, KRAS, FBXW7, MUC6, ERBB2, CTNNB1, and ERBB2 amplifications. One patient with poorly cohesive carcinoma histology harbored a CDH1 mutation. Patients with EBVaGCs with intestinal or poorly cohesive carcinoma histology frequently harbored driver mutations other than PIK3CA, whereas those with EBVaGCs with gastric carcinoma with lymphoid stroma histology lacked other driver mutations. Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (P = 0.005) and combined positive score (P = 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs. [ABSTRACT FROM AUTHOR]

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies. [ABSTRACT FROM AUTHOR]

Background: The presence of atrophic gastritis (AG) and intestinal metaplasia (IM) is associated with an increased risk of gastric cancer (GC). Thus, the development of new strategies to improve AG/IM is essential for reducing the incidence of GC. Aims: We aimed to evaluate the efficacy of rebamipide for improving AG/IM. Methods: This was a prospective, randomized, pilot study from a single tertiary referral center. Fifty-three (rebamipide, n = 34 vs. placebo, n = 19) patients, who underwent endoscopic resection for gastric dysplasia or early GC, were analyzed. We obtained tissue samples from the antrum and corpus of the stomach, at the time of screening and 1-year later. The histologic grading of inflammation was performed by histopathologists Results: The AG grade in the antrum improved significantly after rebamipide treatment (pre-administration, 1.870 ± 0.932 vs. post-administration, 1.430 ± 0.986; P = 0.013). Additionally, the severity of IM in the antrum was significantly improved (pre-administration, 1.750 ± 0.963 vs. post-administration, 1.370 ± 1.032; P = 0.038). The rebamipide subgroup analysis revealed that patients with no Helicobacter pylori (HP) infection showed significant improvements in AG in the antrum (pre-administration, 1.880 ± 1.040 vs. post-administration, 1.250 ± 0.894; P = 0.028) and IM in antrum (pre-administration, 1.840 ± 1.012 vs. post-administration, 1.180 ± 0.912; P = 0.020). Conclusions: This study demonstrated that the administration of rebamipide improves AG and IM in the antrum, especially in patients with HP non-infection (KCT0001915). [ABSTRACT FROM AUTHOR]

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal () were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract (GIT). In fewer than 5% of cases, GIST originates primarily from outside the GIT. The occurrence of GIST originating from the pancreas is rare. Sometimes, neuroendocrine tumors should be differentiated from GISTs because of their hyperenhancing nature in radiologic images. We report a case of GIST arising in the pancreas that was confirmed by surgical resection. [ABSTRACT FROM AUTHOR]

Aims: Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used for these parameters, but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of the consensus process on the assessment of intestinal metaplasia and atrophy. Methods and results: Two study sets were used: consensus and validation. The consensus set was circulated and five gastrointestinal pathologists evaluated them independently using the updated Sydney system. The consensus of the definitions was then determined at the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardise the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through the consensus process (intestinal metaplasia: baseline κ = 0.52 versus final κ = 0.68, P = 0.006; atrophy: baseline κ = 0.19 versus final κ = 0.43, P < 0.001). Higher interobserver agreement in atrophy was observed after consensus regarding the definition (pre‐consensus: κ = 0.19 versus post‐consensus: κ = 0.34, P = 0.001). There was improved interobserver agreement in intestinal metaplasia after standardisation of the grading criteria (pre‐standardisation: κ = 0.56 versus post‐standardisation: κ = 0.71, P = 0.010). Conclusions: This study suggests that interobserver variability regarding intestinal metaplasia and atrophy may result from lack of a precise definition and fine criteria, and can be reduced by consensus of definition and standardisation of grading criteria. [ABSTRACT FROM AUTHOR]

Background: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC).Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-).Results: Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively).Conclusions: Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Aim The vascular endothelial growth factor ( VEGF) or its family might play role in tumor-related angiogenesis in gastrointestinal stromal tumors ( GIST), thereby affecting the prognosis. Accordingly, the present study analyzed the impact of VEGF and VEGF receptor-2 ( VEGFR-2) gene polymorphisms on the prognosis for GIST patients. Methods In all, 213 consecutive patients with GIST from five medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four VEGF (−2578 C/ A, −1498 C/ T, −634 G/ C, and +936 C/ T) and one VEGFR-2 (+1416 A/ T) gene polymorphisms were determined using a Sequenom MassARRAY system. Results With a median follow up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 70 and 87%, respectively. In a multivariate analysis including age, sex, primary site of disease, pathology and risk stratification, no significant association was observed between the polymorphism of the VEGF and VEGFR-2 genes and survival. Conclusion None of the five VEGF and VEGFR-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of VEGF and VEGFR gene polymorphisms as a prognostic biomarker for GIST patients. [ABSTRACT FROM AUTHOR]

Purpose. To assess the efficacy of imatinib for different tumor genotypes in Korean patients with advanced gastrointestinal stromal tumors (GIST). Material and methods. Clinical data were collected from 370 consecutive patients with locally advanced unresectable, metastatic, or recurrent GIST treated with imatinib 400 mg/day between August 2001 and December 2007 at 20 Korean institutions. Tumor genotypes were determined for 290 patients by direct DNA sequencing of KIT exons 9, 11, 13, and 17, and PDGFRA exons 12, 14, and 18. Results. Of 290 patients assessed for genotype, 261 (90.0%) had mutations in KIT: 222 (76.6%) in exon 11, 35 (12.1%) in exon 9 and two each (0.7%) for exons 13 and 17. Four patients (1.4%) had mutations in the PDGFRA gene: one in exon 12, and three in exon 18. Twenty-five patients (8.6%) had no detectable mutations. The best responses of the 235 patients with measurable lesions were: 15 complete response (6.4%), 126 partial response (53.5%), 86 stable disease (36.6%), and eight progressive disease (3.4%). Patients with KIT exon 9 mutations, compared with patients with KIT exon 11 mutations, had a lower objective response rate (36.7% vs. 63.6%, p == 0.007) and a shorter progression-free survival (median 28.7 months vs. 49.4 months, p == 0.001). No statistical difference in overall survival was observed between these genotypes. Conclusion. This study confirms that imatinib efficacy is dependent on genotype in Korean GIST patients, consistent with results demonstrated by Western patients with GIST. [ABSTRACT FROM AUTHOR]

ABSTRACT We report a patient with gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation. A 67-year-old man visited our hospital for further evaluations due to gastric adenocarcinoma. The gastric cancer was located in the prepyloric area and appeared to be a protruding mass with an infiltrative growth pattern. Initial pancreatic and postoperative hepatic and pulmonary metastases were detected radiologically. Microscopically, choriocarcinomatous and hepatoid differentiation was observed with a moderately differentiated adenocarcinoma. The choriocarcinomatous components were positive for β-hCG and the hepatoid components were positive for α-fetoprotein (AFP). These uncommon pathological patterns are supposed to arise from the retrodifferentiation pathway of primary gastric adenocarcinoma. The preoperative laboratory data revealed elevated serum AFP (773.4 ng/mL) and carcinoembryonic antigen (62.2 ng/mL), whereas other tests were unremarkable. The prognosis of gastric adenocarcinoma with choriocarcinomatous and hepatoid differentiation is very poor; our patient died 4 months after the operation. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and aim: Xanthogranulomatous inflammatory reaction (XGI) is a rare diagnosis in the gastrointestinal tract. It could be misinterpreted as an invasive cancerous lesion. The pathogenesis of XGI in the gastrointestinal tract (GIXGI) is not well understood. We clinicopathologically studied six cases of GIXGI associated with endoscopic biopsy, mucosal resection, and submucosal dissection of gastric and colonic adenocarcinoma. Methods: Immunohistochemical, special histochemical stains, and tuberculosis-polymerase chain reaction (PCR) were performed. All radiological images and medical records of the patients were reviewed. Results: All cases showed XGI with foamy histiocytes, lymphocytes, and foreign body-type giant cells, which were positive for CD68 and negative for CD117, S-100, and cytokeratin. Acid-fast, Gomori's methenamine silver, periodic acid Schiff stains, and nontuberculous Mycobacterium and Mycobacterium tuberculosis-PCR were also negative. Two of four gastric adenocarcinomas were suspected to be advanced gastric cancer by computed tomography staging. However, the microscopic examination revealed only XGI with a mucosal carcinoma or without any residual tumor cells in the gastric wall. Conclusions: GIXGI may simulate advanced carcinoma clinicoradiologically. GIXGI should be included in the differential diagnosis in the case suggestive of a rapid transition to advanced gastrointestinal carcinoma within 12 weeks from the preoperative endoscopic procedure. [ABSTRACT FROM AUTHOR]

Background: Since apoptosis plays a key role in cancer progression, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on survival after curative resection in patients with colorectal cancer. Materials and methods: Three hundred and seventy-seven patients were enrolled in the present study. The genomic DNA was extracted from fresh colorectal mucosal tissue, and 15 SNPs of 12 apoptosis-related genes were determined using a Sequenom MassARRAY system. Results: During the median follow-up of 41.8 (range, 1.1-85.5) months patients alive at last follow-up, 65 relapses and 57 deaths occurred. Among the target polymorphisms, the RIPK1 rs2272990 in a dominant model and the CASP7 rs2227310 in a recessive model of the minor allele were associated with survival in a log-rank test. Moreover, the GA+AA genotype of the RIPK1 rs2272990 and the GG genotype of the CASP7 rs2227310 were significantly correlated with a worse disease-free (hazard ratio [HR] = 2.093; P = 0.007 and HR = 2.641; 0.002, respectively) and disease-specific survival (HR = 2.222; P = 0.013 and HR = 2.247; P = 0.031, respectively) in a multivariate survival analysis. Conclusion: The RIPK1 and CASP7 polymorphisms can be considered as possible prognostic markers for survival after curative resection in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]