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Abstract Background Collision tumors are a subtype of simultaneous tumors wherein two unrelated tumors collide or infiltrate each other. Collision gastric adenocarcinomas (CGA) are rare and difficult to diagnose, and their clinical implications remain unclear. Herein, we aimed to reveal diagnostic methods for CGA and provide insight into its implications. Case presentation Among 1041 cases of gastric cancers (GCs) resected between 2008 and 2018, we included cases of confirmed CGA. Patients’ backgrounds, preoperative endoscopy findings, macroscopic imaging findings, and histopathology findings [including immunostaining for CK 7, MUC2, and mismatch repair (MMR) proteins] were investigated. The incidence of CGA was 0.5%: 5 of 81 cases having simultaneous multiple GCs. Tumors were mainly in the distal stomach. The CGA in two cases was between early cancers, in two cases was between early and advanced cancers, and in one case was between advanced cancers. There were three cases of collision between differentiated and undifferentiated types and two cases between differentiated types. Immunostaining with CK7 and MUC2 was useful for diagnosing collision tumor when the histology was similar to each other. Among ten GCs comprising CGA, nine tumors (90%) exhibited deficient MMR proteins, suggesting high microsatellite instability (MSI). Conclusions CGA is rare and usually found in the distal stomach. Close observation of shape, optimal dissection, and detailed pathological examination, including immunostaining, facilitated diagnosis. CGAs may have high MSI potential.

Background: Collision tumors are a subtype of simultaneous tumors wherein two unrelated tumors collide or infiltrate each other. Collision gastric adenocarcinomas (CGA) are rare and difficult to diagnose, and their clinical implications remain unclear. Herein, we aimed to reveal diagnostic methods for CGA and provide insight into its implications. Case presentation: Among 1041 cases of gastric cancers (GCs) resected between 2008 and 2018, we included cases of confirmed CGA. Patients' backgrounds, preoperative endoscopy findings, macroscopic imaging findings, and histopathology findings [including immunostaining for CK 7, MUC2, and mismatch repair (MMR) proteins] were investigated. The incidence of CGA was 0.5%: 5 of 81 cases having simultaneous multiple GCs. Tumors were mainly in the distal stomach. The CGA in two cases was between early cancers, in two cases was between early and advanced cancers, and in one case was between advanced cancers. There were three cases of collision between differentiated and undifferentiated types and two cases between differentiated types. Immunostaining with CK7 and MUC2 was useful for diagnosing collision tumor when the histology was similar to each other. Among ten GCs comprising CGA, nine tumors (90%) exhibited deficient MMR proteins, suggesting high microsatellite instability (MSI). Conclusions: CGA is rare and usually found in the distal stomach. Close observation of shape, optimal dissection, and detailed pathological examination, including immunostaining, facilitated diagnosis. CGAs may have high MSI potential. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the correlation between the clinicopathological features, postoperative treatment, and prognosis of multiple gastric cancers (MGCs). In this study, we aimed to investigate the correlation between these features and the impact of postoperative adjuvant chemotherapy on the long-term survival of patients with MGC. Methods The clinical and pathological data of patients diagnosed with gastric adenocarcinoma who had radical gastrectomy from January 2007 to December 2016 were analyzed. Using propensity score matching, the prognostic differences, and the impact of postoperative adjuvant chemotherapy between those with MGC and solitary gastric cancers (SGC) were compared. Results Among the 4107 patients investigated, the incidence of MGC was 3.2% (133/4107). Before matching, patients with MGC and SGC had disparities in the type of gastrectomy, pathological tumor stage (pT), pathological node stage (pN), and pathological tumor-node-metastasis stage (pTNM). After a 1:4 ratio matching, the clinical data of 133 cases of MGC and 532 cases of SGC were found to be comparable. The 5-year overall survival (OS) rate was 56.6% in the entire matched cohort, 48.1% in the MGC group, and 58.7% in the SGC group (P = 0.013). Multivariate analysis revealed that MGC, age, pT stage, pN stage, and adjuvant chemotherapy were independent predictors of OS (all P

• It is unclear how Epstein–Barr virus causes cancer. • EBVaGC should be considered when multiple gastric cancer is recognized. • Robotic surgery has high-resolution three-dimensional images. • Using forceps with multi-joint functions was effective for this case. Epstein–Barr virus-associated gastric cancer (EBVaGC) sometimes appears as multiple gastric cancer lesions. Here, we report a case of robot-assisted laparoscopic total gastrectomy (RTG) for a relatively rare disease with four synchronized lesions in EBVaGC and discuss the usefulness of robotic gastrectomy. A 60-year-old woman was diagnosed with multiple gastric cancer because she had five lesions in the stomach and biopsy showed the presence of adenocarcinoma in four of the five lesions. We performed robot-assisted laparoscopic total gastrectomy on the patient. The histopathological diagnosis was multiple gastric cancer T1bN0M0 pStage IA. The four lesions were positive for the Epstein–Barr virus encoding region in in-situ hybridization and were considered to be EBVaGC. The patient had no sign of recurrence without postoperative therapy for 24 months. EBVaGC was found in about 10% of all gastric cancer cases worldwide. EBVaGC sometimes appears as multiple gastric cancer, suggesting that EBV infection is closely related to the early stages of tumor formation. Total gastrectomy may be necessary for multiple gastric cancer such as EBVaGC, and robotic surgery is useful in total gastrectomy in terms of high-resolution three-dimensional images and using forceps with multi-joint functions. We performed RTG on a patient with four synchronous lesions of EBVaGC, which is relatively rare. Robot-assisted laparoscopic total gastrectomy is known to be a safe procedure, and we effectively performed total gastrectomy for multiple EBVaGC. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to define differences between synchronous multiple gastric cancer (MGC) and solitary gastric cancer (SGC) and to evaluate the characteristics of missed lesions in MGC so as to improve the detection rate of missed lesions during perioperative procedure. Methods: The authors retrospectively analysed data on 9157 gastric cancer patients who underwent gastrectomy for gastric cancer in a single hospital. The characteristics of 8893 SGC and 264 MGC patients were evaluated. The characteristics of missed lesions in MGC were compared with those of diagnosed lesions found in preoperative endoscopy. Results: Of the 9157 gastric patients, 264 patients with MGC showed a total of 565 cancer lesions, 70 of which were missed at endoscopy. The patients with MGC demonstrated different characteristics compared with those with SGC in terms of sex, age, type of operation, depth of tumour, lymph node metastasis, tumour size, tumour location and curability ( P < 0.05). The characteristics of the missed lesions ( n= 70) were a small size ( P < 0.05), a middle one-third location ( P < 0.001) and a flat type by macroscopic examination ( P < 0.05) as compared with detected lesions ( n= 495). No survival difference was detected between patients with and without missed lesions over a mean follow-up of 36.0 ± 22.7 month. Conclusions: Preoperative gastroscopy should be performed meticulously in the entire stomach, especially in older men, in order to identify the presence and locations of cancer lesions that might otherwise be missed. [ABSTRACT FROM AUTHOR]

Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI. [ABSTRACT FROM AUTHOR]

Clinicopathological study was given to 100 early gastric cancer cases. The cases included 50 intramucosal lesions (m-group) and 62 submucosal lesions (sm-group), and the share is 17% of whole cases treated surgically. The sex ratio is about 2:1 (male: female). According to the classification by location, the occurrence rate of lesion on anterior wall is 18.8%. This fact suggests the impotance of roentgenscopy by compression technique and double contrast in a prone position focussed on anterior wall. In addition, endoscopy is essential in order to detect minute cancers. The rates of metastasis of early gastric cancers is 2.4% of m-group and 16.1% of sm-group. No metastasis occurs in protruded or elevated type as far as cancer cells remain within the mucosa. Once cancer cells infiltrate into the submucosa, metastasis is oberserved in 36%. In the present cases, 9 (9%) out of 100 cases of early gastric cancers are the multiple cases. In order to avoid oversight of cancer foci, the portion of stomach to be remained after surgery should be throughly examined prior to operation and again under direct vision after gastric incision. [ABSTRACT FROM AUTHOR]

Rationale : Multiple gastric cancer (MGC) is characterized by the presence of more than two different tumors in the stomach. However, the clonal relationship and carcinogenesis of MGC remain unclear. We investigated the clonal relationship and role of germline mutations in the carcinogenesis of MGC. Methods: We gathered 16 multiple gastric cancer patients. Thirty-three tumor samples and sixteen normal gastric tissue or blood samples were obtained from January 2016 to December 2017. We also conducted analyses for 208 gastric cancer and 49 esophagogastric junction cancer (GC-EGJ) tumors from TCGA. DNA extraction from our samples was conducted for whole-exome sequencing (WES). Results : Tumor mutation burden (TMB) was not statistically significant within database and our data in the GC-EGJ (P=0.0591) and GC groups (P=0.3113). The mutation spectrum and signatures also showed uniform distributions in GC and GC-EGJ groups within our data and TCGA database. Among sixteen patients, four were identified as monoclonal, in which 11, 10, 26 and 6 somatic mutations were shared within different tumors of P7, P8, P9 and P16, respectively. However, no common mutation between different tumors of the same patient was found among the other 12 patients. After identifying predisposing genes, we found that germline MSH2 and NCOR2 mutations were significantly dominant in 8/12 and 10/12 of genetic MGC patients. Additionally, all patients were identified with MSH2 mutations in cancer samples of those genetic MGC patients. Taking genetic MGCs as a whole, we identified that TP53 were significantly mutated in 14 of 25 tumor samples. Main conclusions : WES analyses are suggestive of monoclonal and polyclonal origin of MGC, which may promote the classification of MGC into genetic and metastatic MGC. For patients with genetic MGC, germline MSH2 X314 &#95;splice variants may contribute to carcinogenesis, thus prompting the consideration of more radical surgery and/or anti-PD-1/PD-L1 therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The development of multiple gastric cancer is a major problem after the endoscopic resection of the first early gastric cancer. To find out markers to identify high risk patients, we analyzed the microsatellite instability (MSI) status and hypermethylation of tumor-related genes in multiple gastric cancers. Sixty-four adenocarcinomas resected by endoscopy, including 32 early solitary gastric cancers (SGCs) from 32 patients and 32 multiple gastric cancers (MGCs) from 14 patients, were employed. We analyzed MSI and the methylation status of promoter regions of the hMLH1, MGMT, p16 and E-cadherin using methylation-specific Polymerase Chain Reaction. Expression levels of hMLH1 were examined by immunohistochemistry. MSI (+) was detected in 5 of the 14 (35.7%) patients with MGCs, and in only 3 of the 32 patients (9.3%) with SGCs. Significant differences were observed between the 2 groups (p<0.001). Hypermethylation of hMLH1 was more frequently detected in MGCs than in SGCs (p<0.01), whereas significant difference was not observed in the frequency of MGMT, p16 or E-cadherin promoter methylation between the 2 groups. In conclusion, our results indicate that inactivation of hMLH1 through promoter hypermethylation may be involved in the development of multiple gastric cancers following the MSI pathway.