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The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A 66-year-old Japanese man receiving systemic chemotherapy for advanced gastric cancer presented with exertional dyspnea. D-dimer was elevated in the blood. Echocardiography revealed pulmonary hypertension, and a ventilation-perfusion scan indicated decreased perfusion in the bilateral lungs. Cardiac catheterization showed no evidence of pulmonary artery embolization and revealed cytologically confirmed adenocarcinoma. Thus, pulmonary tumor thrombotic microangiopathy (PTTM) was diagnosed. The patient died of respiratory failure on the 17th hospitalization day despite systemic chemotherapy. Retrospective serological testing revealed increased vascular endothelial growth factor in the pulmonary artery blood. This is a rare case with antemortem cytologically proven PTTM mediated by VEGF.

Intratumoral HER2 heterogeneity is a well-described gastric cancer feature and may explain many false-negative results related to this oncogene. An 81-year-old man was diagnosed at our hospital with stage IV gastric cancer with multiple lymph node metastases. Immunohistochemistry (IHC) analysis indicated that the primary tumor was HER2-negative. After a chemotherapy course, we submitted a pretreatment biopsy specimen for comprehensive cancer genome profiling (CGP) to determine the last-line therapy. This revealed HER2 amplification. The specimen was reevaluated using fluorescence in situ hybridization and IHC with deeper-cut specimens, which confirmed that the tumor was indeed HER2-positive. Therefore, the patient was treated with chemotherapy plus trastuzumab, which elicited tumor shrinkage and conferred long-term survival. Our current data underscore the CGP importance, which can provide more accurate tumor profilings and inform subsequent treatment decisions.

Background and Aims: Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups., Methods: Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined., Results: Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features., Conclusions: Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Hand-assisted laparoscopic surgery is considered to provide the benefits of laparoscopic surgery in various diseases. However, limited information is available regarding the feasibility of hand-assisted laparoscopic distal gastrectomy (HALDG)-a subset of hand-assisted laparoscopic surgery-as a gastric cancer treatment. This study aimed to evaluate the usefulness of HALDG compared with laparoscopy-assisted distal gastrectomy (LADG). Consecutive patients who underwent HALDG (n=58) or LADG (n=90) for stage I gastric cancer between 2005 and 2016 were eligible. Operative time was significantly shorter and blood loss was significantly higher in HALDG than in LADG (P<0.001, both). Postoperative aminotransferase levels were significantly lower in HALDG than in LADG (P<0.001). There was no significant difference in perioperative complications, a number of analgesics, postoperative C-reactive protein levels, and 3-year relapse-free and overall survival rates between the groups. This study suggests that HALDG is a safe and feasible approach and could become an effective option for stage I gastric cancer treatment.

As gastric neuroendocrine carcinoma (NEC) is a rapidly growing cancer, most cases are diagnosed at advanced stages. We herein report a 74-year-old woman with an early-stage gastric NEC whose history included endoscopic submucosal dissection treatment for three early-stage gastric cancer lesions five years prior to the current presentation. We also describe the changes observed over time. An endoscopic examination during follow-up revealed an NEC (measuring 6 mm) in the gastric vestibule, for which distal gastrectomy was performed. Four months before surgery, the carcinoma exhibited specific morphological changes and lymphovascular invasion (despite the tumor being stage 1), suggesting a high-grade NEC.

Background: Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC., Methods: We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation., Results: Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC 50 values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1., Conclusions: Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.

A 37-year-old male with tarry stool presented to our hospital. Esophagogastroduodenoscopy revealed advanced gastric cancer, fundic gland polyposis (FGPsis), and negativity for Helicobacter pylori (HP) infection. Computed tomography exhibited multiple liver tumors. Total colonoscopy (TCS) demonstrated 139 tubular adenomas. He was diagnosed as having unresectable gastric cancer and received systemic chemotherapy. His sister and mother had colorectal adenomatous polyposis as revealed by TCS. His sister had FGPsis and was negative for HP infection, whereas his mother had early gastric cancer with HP infection but not FGPsis. Genetic analysis revealed a novel mutation in exon 15 of the APC gene (NM&#95;000038.5: c.7647&#95;7648&#95;delTG) for the patient, his mother, and his sister, whereas no mutation was found for his father who had no gastrointestinal polyps. Therefore, the pedigree was diagnosed as an FAP family with a novel APC germline mutation which had different gastric phenotypes depending on the status of HP infection.

A 77-year-old woman was admitted to our hospital with complaints of lumbago. Based on MRI, bone marrow biopsy, and upper endoscopy, she was diagnosed as having advanced gastric cancer accompanied by bone marrow metastasis and multiple bone metastases. She underwent combination chemotherapycontaining S-1 and docetaxel(TXT). However, during the first course of chemotherapy, she developed Grade 4 neutropenia and sepsis, and her ADL worsened. The anticancer agent doses were reduced drasticallyto 40% of the initial dose from the next course of chemotherapy. She was able to continue treatment without developing severe adverse events, and the disease did not progress for 11 months. However, during the 6 course of chemotherapy, she developed Grade 4 neutropenia and sepsis again, and it became difficult to continue treatment. Subsequent S-1 monotherapywas not efficacious, and she died 17 months after diagnosis. From the view of persistence and efficacy, we believe that low-dose combination chemotherapycontaining S-1 and TXT maybe a suitable regimen for advanced gastric cancer with bone marrow metastasis.

Purpose: The aim of this study was to determine the recommended dose (RD) for a docetaxel/oxaliplatin/S-1 (DOS) regimen in patients with unresectable gastric cancer and to preliminarily evaluate its efficacy., Methods: Previously untreated patients with histologically proven unresectable metastatic gastric cancer were enrolled (n = 16). Docetaxel and oxaliplatin were administered intravenously on day 8 and S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle. Three dose escalations of DOS were employed in this study: level 1 (50/100/80 mg/m 2 ), level 2 (50/130/80 mg/m 2 ), and level 3 (60/130/80 mg/m 2 )., Results: According to the 3 + 3 dose-escalating schedule, we determined that the RD and maximum tolerated dose for this regimen were level 1 and level 2, respectively. The DLTs were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) for patients with measurable lesions and consisted of two complete responses and five partial responses. Five patients underwent conversion surgery. The median follow-up time was 19 months with median survival time and progression-free survival being 19.6 months and 7.6 months, respectively., Conclusions: The results from this study demonstrated the safety and tolerability of DOS in unresectable metastatic gastric cancer patients and revealed promising preliminary efficacy with a high conversion rate. A phase II trial of DOS regimen using the identified RD is ongoing.

A 48-year-old Japanese female with left hypochondralgia presented at our hospital. Esophagogastroduodenoscopy (EGD) revealed gastric cancers and carpeting fundic gland polyposis (FGPs) without Helicobacter pylori infection. Computed tomography showed multiple liver metastases. Total colonoscopy revealed a colonic tubular adenoma but not polyposis. She was diagnosed as having advanced gastric cancer with liver metastasis and received chemotherapy. Her mother had died from gastric cancer, and her elderly brother and niece had FGPs as revealed by EGD. Thus, the pedigree was diagnosed as gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Germline mutation analysis exhibited a point mutation in exon1B of the APC gene (c.-191T > C). Adenocarcinoma showed a gastric mucinous phenotype and was positive for a somatic mutation of p53, suggesting that p53 mutation may play a role in FGPs carcinogenesis. This is the first family with GAPPS in Asia in whom germline mutation of APC exon 1B has been detected.

Purpose: Peritoneal metastasis (PM) in advanced or recurrent gastric cancer (AGC) is the most frequent cause of death from this disease. However, current treatments remain unsatisfactory. We previously conducted studies of docetaxel, cisplatin and S-1 (DCS) combination chemotherapy for AGC. The aim of this study was to investigate the benefits and tolerability of DCS in PM patients., Methods: Patients were divided into three groups: patients without PM (non-PM); PM patients without ascites, or mild to moderate ascites (None-Mod); and PM patients with massive ascites (Massive). Patients received oral S-1 (40 mg/m 2 b.i.d.) on days 1-14, and intravenous cisplatin (60 mg/m 2 ) and docetaxel (50-60 mg/m 2 ) on day 8 every 3 weeks. Drug exposure, adverse events, tumor response, progression-free and overall survival (OS) rates were evaluated., Results: Of the 111 AGC patients who received DCS as first-line therapy, 37 cases had complicated PM, 15 of whom displayed massive ascites. The response rate for PM patients was 81.5%. Drug exposure and toxicities were not meaningfully different among the groups. The MSTs were also similar: 22.6 months for the non-PM, 21.7 months for the None-Mod PM, and 16.8 months for the Massive, respectively. Ten (27.0%) patients with PM achieved downstaging and underwent curative surgery, subsequently demonstrating an excellent MST of 28.0 months. An independent prognostic factor for OS, as revealed by multivariate analyses. was a good performance status., Conclusion: DCS is feasible and efficacious for AGC with PM, especially when patients present with a good PS.

We present here a case of transduodenal ampullectomy for an ampullary neoplasm coexisting with gastric and colon cancer. The patient was a 72-year-old man who was referred to our hospital with a positive fecal blood test. Colonoscopy revealed advanced cancer in the descending colon. As part of the preoperative examination, for the colonic cancer, upper gastrointestinal endoscopy was performed. Endoscopy showed a 2 cm elevated lesion(0'-II a type)with subserosalinfil tration on the small curvature side of the upper part of the stomach, and a 2 cm elevated lesion on the papilla of Vater. Histopathological examination showed that the former was a well differentiated tubular adenocarcinoma and the latter was a villous tubular adenoma with severe atypia. First, laparoscopic colectomy for advanced descending colon cancer was performed. Totalgastrectomy with Roux-en-Y reconstruction, cholecystectomy, and transduodenal ampullectomy for the ampullary neoplasm 21 days after the first surgery. The patient was discharged without any complications, such as postoperative suture failure. According to pathological tissue diagnosis, the degrees of progress of the colorectal cancer and the gastric cancer were pT2(MP)and pT1b(SM2), respectively, and there was no lymph node metastasis. The duodenal papillary tumor was a tubular villous adenoma(high grade). Local excision of the papilla is minimally invasive, leaves easy-to-secure stumps, and has less risk of complications such as bleeding and pancreatitis. Taking into account the balance with coexisting gastrointestinal cancer treatment, local excision of the papilla in this case was considered to be an appropriate treatment.

We report a 72-year-old woman with rare metastases of gastric cancer to the bone, skin, and ovary occurring more than 8 years after distal gastrectomy, which were subsequently effectively controlled. Histopathological diagnosis revealed signetring cell carcinoma, and the comprehensive findings were pT4a, pN3, ly2, v0, and Stage III c. The adjuvant chemotherapy of S- 1 plus cisplatin(CDDP)was switched to S-1monotherapy for 4 years and then to tegafur/uracil(UFT)for an additional year. Eight years after the operation, I-CTP and alkaline phosphatase(ALP)levels were elevated, and bone scintigraphy revealed bone metastasis. The patient's ALP levels, which had increased to 6,617 U/L, remarkably decreased to 359 U/L 17 months after treatment with zoledronic acid. About 9 years after the operation, a 2cm subcutaneous node was seen on the patient's scalp, and a biopsy was performed. Histologically, the node was confirmed as a signet-ring cell carcinoma. S-1 therapy was initiated, and the node disappeared within 8 months. About 10 years after the gastrectomy, abdominal computed tomography( CT)scans indicated a tumor sized 11×10 cm in the pelvis, and a biopsy was performed. Histologically, the tumor was a signet-ring cell carcinoma appearing as an ovarian metastasis of gastric cancer. Ovariectomy was performed. Peritoneal dissemination was not detected. The patient was treated with S-1 plus oxaliplatin and zoledronic acid, and continues to remain in good condition 9 months after the ovariectomy.

Purpose: Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen., Methods: Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m 2 b.i.d) on days 1-14, and docetaxel (50 mg/m 2 ) plus cisplatin (60 mg/m 2 ) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated., Results: Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%)., Conclusion: Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.

Background: Performing a safe esophagojejunostomy is important for the standardization of laparoscopic total gastrectomy. We have performed intracorporeal esophagojejunostomy by a circular stapler using the purse-string suturing device that we co-developed. The advantage of this device is that it makes use of the same surgical procedure as open surgery, but it does not depend on the surgeon's technical skills since this device does not require the laparoscopic hand-sewn technique. Furthermore, we have also adapted this device for double-tract reconstruction after laparoscopic proximal gastrectomy. In this study, we present the surgical procedures and postoperative short-term outcomes that were obtained using this novel technique., Methods: We enrolled 94 patients that underwent intracorporeal esophagojejunostomy by circular stapler using our device after laparoscopic total or proximal gastrectomy for gastric cancer between November 2009 and October 2016., Results: Postoperative complications related to esophagojejunostomy were due to anastomotic stenosis in two cases (2.1%) and leakage of the jejunum stump in one case (1.1%)., Conclusions: Intracorporeal esophagojejunostomy by circular stapler using the purse-string suturing device is safe and feasible. This method can be one of the standard procedures for performing intracorporeal esophagojejunostomy.

A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient's malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs). In this study, we analyzed CTCs of patients with gastric cancer (GC) to find those who were likely to benefit from trastuzumab therapies. We developed an imaging-based method that enabled CTC identification simultaneously with evaluation of HER2 gene amplification (the 3D-IF-FISH method). Then we performed a study enrolling 101 GC patients in whom we analyzed CTCs by both 3D-IF-FISH and an FDA-approved CellSearch system. As compared with the CellSearch system, 3D-IF-FISH methods identified a higher number of patients whose primary tumors were HER2- but who had HER2+ CTCs, suggesting that the 3D-IF-FISH method is effective in preselecting patients for trastuzumab therapies. To demonstrate this, we performed an exploratory clinical study to evaluate the clinical benefits of trastuzumab treatment for advanced GC patients (n = 15) whose primary tumors were HER2-, but whose CTCs showed HER2 amplification. An interim evaluation after the first stage showed that these preselected patients had response rates comparable to those reported in the trastuzumab-plus-chemotherapy arm of the ToGA study. The present study offers a new, non-invasive strategy to select patients who are likely to benefit from trastuzumab-based therapies, despite their primary biopsy being HER2-negative. (UMIN ID: UMIN000008622).

Background: Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes., Methods: One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m 2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m 2 ) and docetaxel (50-60 mg/m 2 ) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery., Results: Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS., Conclusions: DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.

Objectives: We conducted a phase II trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by extensive resection in the management of resectable locally advanced gastric cancer with lymph node (LN) metastases., Methods: Patients with LN metastases from stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN metastases were the involvement of ≥4 nodes <2 cm or ≥1 nodes ≥2 cm as confirmed by a total body computed tomography scan. All patients underwent extensive resection including D2 gastrectomy. The primary endpoint was complete resection rate and the secondary endpoints were 3-year relapse-free and overall survival., Results: Fifty patients were assessable for the analysis. The complete resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year overall survival rate was 48.0%., Conclusions: NAC with S-1 and CDDP is safe and may improve the complete resection rate in patients with metastatic LN gastric cancer. This suggests that LN metastases would provide good target lesions in future clinical trials of NAC.

Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.

Objectives: The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy., Methods: Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy., Results: Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays., Conclusion: The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy., (© 2017 S. Karger AG, Basel.)

Background: Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes., Methods: Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed., Results: BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002)., Conclusions: BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.

Background: The aim of this study was to investigate the impact of being underweight on the long-term outcomes of gastric cancer patients., Methods: This study reviewed the medical records of 638 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2011. The patients were divided into three groups according to the WHO classification: underweight (BMI <18.5 kg/m(2)), normal weight (BMI ≥18.5 and <25 kg/m(2)), and overweight (BMI ≥25 kg/m(2)). A multivariate analysis was performed to identify prognostic factors., Results: The mean BMI immediately before surgery was 22.5 kg/m(2) (standard deviation, 3.3 kg/m(2)). According to the BMI subgroup, 73 patients (11.4 %) were underweight, 431 patients (67.6 %) were of normal weight, and 134 patients (21 %) were overweight. The 5-year overall survival (OS) rate was 66.6 % in the underweight patients, 81.3 % in the normal weight patients, and 79.9 % in the overweight patients (P = 0.001). The OS rate was significantly lower in the underweight patients than in the normal weight and overweight patients among those with stage I disease, and it was also lower than in the normal weight patients among those with stage II and III disease. In the multivariate analysis, being underweight was found to be an independent predictor of OS, but it was not an independent predictor among patients with stage II and III disease., Conclusions: Being underweight is a simple and reliable predictor of a worse long-term outcome among gastric cancer patients. Being underweight is considered to be associated with a higher risk of non-cancer death.

A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years.

Purpose: To evaluate the incidence of major adverse cardiac events (MACE) and long-term surgical outcomes after gastrectomy for gastric cancer using the revised cardiac risk index (RCRI), which is based on preoperative insulin use, serum creatinine >2.0 mg/dL, and history of ischemic or congestive heart failure or cerebrovascular disease., Methods: We allocated 1000 patients who underwent elective gastrectomy to three groups with ≥3 (group A, n = 32), 2 (group B, n = 142), or 1 (group C, n = 826) of these factors and compared surgical complications and prognoses., Results: Groups A and B had older patients than group C. Group B had more male patients than groups A and C. Tumor staging and gastrectomy type were similar among all groups. D1 lymph node dissection was more frequent in group A than in groups B or C. The incidence of MACE in groups A, B, and C was 25.0, 9.9, and 1.1 %, respectively. RCRI was associated with MACE. Furthermore, the incidence of pneumonia and in-hospital mortality was associated with RCRI risk factors. However, the incidence of anastomotic leakage, intra-abdominal abscess, wound infection, and pancreas-related infection were similar among the groups. The 5-year overall survival rates of the three groups were 44.3, 65.2, and 80.8 %, which were significantly different., Conclusions: Patients with RCRI factors have an increased risk of MACE, pneumonia, and higher mortality after gastrectomy; thus, careful patient selection and meticulous perioperative care are crucial for successful gastrectomy.

Postoperative adhesion is a frequent problem in patients undergoing surgery. In particular, gastrectomy is associated with a high risk of bowel obstruction. However, there are few reports of small bowel obstruction (SBO) after gastrectomy in the English-language literature. We reviewed the literature to assess the effectiveness of various techniques for preventing adhesion in patients treated with gastrectomy. We assumed that strategies used to prevent postoperative adhesion associated with colorectal surgery, cholecystectomy, appendectomy and gynecologic procedures are similar to those used in gastrectomy. We therefore reviewed reports on the prevention of postoperative SBO in any abdominal surgical procedure, focusing especially on gastrectomy. General intraoperative preventive techniques, such as the use of starch-free gloves, saline irrigation at a temperature below 37 °C and laparoscopic techniques whenever possible, may reduce the incidence of SBO in patients with gastric cancer who undergo gastrectomy. If preserving the omentum is unrelated to the survival rate of patients with gastric cancer, this technique should be recommended for preventing postoperative SBO. The use of hyaluronic acid/carboxymethylcellulose bioabsorbable membranes should also be considered in patients undergoing gastrectomy. However, demonstrating the advantages of bioabsorbable membranes would require larger randomized studies with a longer follow-up period.

Background and Aim: Objective evaluation of intestinal mucosal damage due to anticancer drugs is generally difficult. Serum diamine oxidase (DAO) activity is reported to reflect the integrity and maturity of the small intestinal mucosa. Therefore, we investigated whether serum DAO activity is an indicator of gastrointestinal toxicity or nutritional status in patients receiving chemotherapy., Methods: We prospectively enrolled 20 patients with unresectable metastatic gastric cancer who received oral S-1 (80 mg/m(2) ) on days 1-14, and intravenous cisplatin (60 mg/m(2) ) and docetaxel (50 mg/m(2) ) on day 8 every 3 weeks. Serum DAO activity was measured by colorimetry. Gastrointestinal toxicity was evaluated by Common Toxicity Criteria for Adverse Events version 4.0. Endoscopic examination and biopsy of duodenal mucosa assessed mucosal damage. Malnutrition was evaluated by measuring serum total protein and albumin levels., Results: Serum DAO activity decreased step-by-step significantly during anticancer drug treatment and recovered after drug holidays. In all 14 patients who experienced diarrhea, serum DAO activity significantly decreased prior to diarrhea onset. Percent decrease in DAO activity was significantly correlated with severity of diarrhea. Significant correlation was observed between percent decrease in DAO activity and percent decrease in duodenal villus height or surface area from baseline. There were also significant correlations between percent decrease in serum DAO activity at day 14 and percent decrease in serum total protein or albumin levels at day 21 from baseline., Conclusion: Serum DAO activity sensitively indicates gastrointestinal damage prior to symptom onset and can be a useful predictor of intestinal mucosal damage and nutritional status in patients receiving chemotherapy., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Purpose: We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer., Methods: Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks., Results: The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months., Conclusions: DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation., Clinical Trial Registration Number: UMIN000005603.

Background/aims: The aim of this study was to evaluate the surgical outcomes after palliative surgery for patients with incurable gastric cancer., Methodology: This retrospective study included 45 patients with gastric outlet obstruction (GOO) who needed parental nutrition and 33 patients with anemia due to tumor bleeding who required blood transfusions. We compared the surgical outcomes of palliative gastrectomy (PG) and bypass surgery (BS) in each group., Results: In the GOO patients, the clinical success rate, as indicated by a resumption of an oral diet, was similar in the PG and BS groups. The time to treatment failure, when the GOO patients again required parental nutrition, was also similar between the two groups. In the anemia patients, the clinical success rate of the PG group was higher than that of BS group, and the post-operative performance status (PS) of the PG group was also better than that of the BS group, although the pre-operative PS were similar in both groups., Conclusions: PG for the GOO patients gave little advantage compared to BS, and was associated with a longer operation, higher blood loss and more frequent complications. PG may be recommended for patients with GOO when they simultaneously have anemia due to tumor bleeding.

Cronkhite-Canada Syndrome (CCS) is a rare non-inherited gastrointestinal polyposis syndrome with characteristic ectodermal changes. We report an extremely unusual case of CCS associated with primary esophageal and gastric cancers. A 74-year-old Japanese man with symptoms of anorexia and diarrhea was found to have primary esophageal and gastric cancers, as well as multiple gastric and colonic polyps. Based on the physical findings of onychodystrophy and alopecia, we diagnosed CCS. Because of his age and nutritional status, we decided to perform total gastrectomy for gastric cancer and chemoradiotherapy for esophageal cancer, upon completion of which the patient was started on steroid therapy for the CCS. After 1 week of steroid therapy, the patient's watery diarrhea improved. We recommend that for patients with CCS, the therapeutic strategy be carefully considered based on the patient's nutritional status, the severity of the CCS, and the extent of gastrointestinal cancer.

A 60-year-old male presented to our hospital for further investigation of abnormal findings on an upper gastrointestinal series. Esophagogastroduodenoscopy demonstrated atrophic gastritis and a submucosal tumor (SMT) at the anterior wall of the antrum. The patient was positive for serum anti-Helicobacter pylori (H. pylori) antibody and H. pylori eradication therapy was performed. Five months later, the SMT showed a remarkable morphological change in that an ulcer had developed on its apex, and partial gastrectomy was performed. Pathological examination suggested an inflammatory fibroid polyp (IFP), and genetic analysis revealed no mutation in the platelet-derived growth factor receptor alpha gene. This case suggests that H. pylori infection plays an important role in the etiology of IFPs.

Gastric neuroendocrine tumor (NET) is sometimes found as a submucosal tumor on upper gastrointestinal endoscopy. Gastric NET with malignant profile and neuroendocrine carcinoma (NEC) show various forms which are difficult to distinguish from gastric cancer and other disease. We report a case of a cauliflower-shaped NET of the stomach. A 61-year-old man was referred to our hospital with a complaint of abdominal fullness. Upper gastrointestinal endoscopic examination revealed an unusual, whitish cauliflower-shaped tumor that belongs to Borrmann type I on the lesser curvature of the gastric antrum. Histological examination of the biopsy specimen revealed NET G2, because the tumor cells were CD56- and synaptophysin-positive by immunohistochemical analysis. A distal gastrectomy with D2 lymphadenectomy was performed. A recurrence in the liver was revealed by follow up computed tomography after 11 months from operation. Combined chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP) was treated. The patient achieved a partial response, but he died after 31 months from gastrectomy. There is no independent, large-scaled prospective study and no standard treatment for gastric NETs with distant metastases. Our case is reported with a literature review of the treatment of metastatic gastric NET G2.

Purpose: Pylorus-preserving nearly total gastrectomy (PPNTG) is a function-preserving gastrectomy for treating proximal early gastric cancer that prevents rapid gastric emptying and reflux. In this report, we present a surgical technique for performing laparoscopy-assisted PPNTG (LAPPNTG)., Methods: The resection of the stomach was similar to that during conventional total gastrectomy, with the key difference being that the pyloric cuff was preserved to a length of 3-4 cm. Compared with standard total gastrectomy, the lymph node dissection along the right gastric vessels and the infrapyloric vessels were omitted. Reconstruction was performed with a jejunal interposition that was 30 cm in length, with preservation of the marginal vessels in a retrocolic fashion., Results: Thirteen patients with cT1 cN0 proximal gastric cancer underwent LAPPNTG at our institution. The median length of the operation and estimated blood loss were 329 min and 138 ml, respectively. All resected specimens had tumor-free margins, and the median number of removed lymph nodes was 40. There were no serious postoperative complications and no patients underwent conversion to laparotomy., Conclusions: Performing LAPPNTG with a jejunal interposition is feasible and might be an appropriate treatment for proximal early gastric cancer.

Since 2011, we have performed routine staging laparoscopy on 7 patients presenting with type 4 gastric cancer at our department. After staging laparoscopy, the patients received neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS). After the completion of 2 courses of chemotherapy, radical gastrectomy with D2 gastrectomy or greater was performed, followed by postoperative adjuvant chemotherapy with S-1 for 1 year. In the present study, we evaluate the outcomes of the treatment strategies for the type 4 gastric cancer patients treated at our institution. Staging laparoscopy and peritoneal lavage cytology revealed that none of the patients had peritoneal metastasis, while peritoneal cytology detected carcinoma cells in 3 patients. Grade 3 or greater neutropenia developed in 3 patients, and Grade 3 or greater nonhematological toxicity developed in 3 patients after neoadjuvant chemotherapy. The disease control rate was 100% and all patients underwent radical gastrectomy. Of the 3 patients who had positive peritoneal cytology on staging laparoscopy, 2 patients had no peritoneal cancer cells at the time of gastrectomy. Six patients underwent R0 surgery after DCS chemotherapy, and the response rate was 57.1%. The median survival time was 540 days. Four patients experienced peritoneal recurrence, and 1 developed lymph node recurrence. Our therapeutic strategy for type 4 gastric cancer contributed to prolonged survival; however, it is necessary to develop better strategies that can prevent or control the peritoneal recurrence.

We report here an experience treating a patient who developed gastric cancer at the same time as a multifocal intrahepatic recurrence of hepatocellular carcinoma (HCC). The patient was a 76-year-old woman who underwent partial liver resection after diagnosis of HCC in August 2008. Histopathological examination revealed moderately differentiated hepatocellular carcinoma and stage III pathology. Six months following surgery, an upper gastrointestinal endoscopy revealed a typeIIa+IIc gastric tumor in the angle of the stomach, which was pathologically diagnosed as adenocarcinoma(por2/sig) in the biopsy. Simultaneously, abdominal CT scan revealed multifocal intrahepatic recurrence of HCC, so Lip-TACE as performed. Eight days after TACE, S-1 (80 mg/body) was initiated. About one month after TACE, abdominal CT scan revealed multiple new hepat- ic lesions. The patient was repeatedly treated with a combination of Lip-TACE on day 1 and S-1 80 mg/body/day, administered on days 8 to 35 for 28 days, followed by a 7 day interval as 1 course. After 5 courses of medication of S-1, liver function had deteriorated and thrombocytopenia occurred. Although there was no progression of gastric cancer, medication of S-1 was discontinued. Lip-TACE was performed nine times. About one year after the initial TACE, the patient was admitted to our hospital in order to control ascites, 3 days after admission, she suffered a cerebral infarction and died 3 days later.

Background: RING box protein-1 (RBX1) is an essential component of the E3 ubiquitin ligase Skp1/Cullin/RBX1/F-box protein complex. Although an altered expression of RBX1 has been reported in several human cancers, the role of RBX1 in gastric cancer remains unknown., Methods: We investigated the RBX1 expression in primary gastric cancer tissues from 145 patients by immunohistochemistry, and explored its clinical relevance and prognostic value. Furthermore, the effect of RBX1 expression on cancer cell proliferation was analyzed in vitro using a siRNA silencing technique., Results: The RBX1 expression was abundant in gastric cancer tissues. There was a significant difference in the expression level of RBX1 in terms of the tumor depth (P = 0.008), presence of distant metastasis (P = 0.016) and venous invasion (P = 0.005). The postoperative overall (P < 0.001) and relapse-free survival (P < 0.001) rates were significantly poorer in patients with RBX1-high tumors than in patients with RBX1-low tumors. There was a significant correlation of the RBX1 status with postoperative hematogenous recurrence (P = 0.013). Importantly, the RBX1 status was identified as an independent prognostic factor for gastric cancer (P = 0.002). Furthermore, RBX1 gene silencing significantly inhibited the proliferation of gastric cancer cells in vitro., Conclusions: The RBX1 expression has a significant prognostic value in gastric cancer. RBX1 might play an important role in regulating the proliferation of gastric cancer cells and promoting the development of postoperative recurrence. Our data provide a rationale for developing a novel therapy targeting RBX1 for gastric cancer.

Background: The incidence of chronic kidney disease (CKD) is increasing, which might be an obstacle to various aspects of gastric cancer treatment, such as perisurgical management and postsurgical follow-up. The present study aimed to evaluate the short- and long-term surgical outcomes following gastrectomy in patients with CKD., Methods: We retrospectively analyzed surgical complications and prognosis of patients with gastric cancer. These patients were divided into three groups according to the glomerular filtration rate (GFR): 49 patients with severe CKD (GFR < 29 ml/min/1.73 m(2)), 128 with mild CKD (GFR 30-59), and 798 in the controls (GFR ≥ 60)., Results: The incidences of anastomotic leakage and intraabdominal abscess in the mild and severe CKD groups were higher than that in the control group. The incidences of wound infection, cardiovascular and pulmonary events, and in-hospital mortality in the severe CKD group were higher than those in the other two groups. Severe surgical complications were associated with co-morbidities other than CKD, serum albumin level, estimated blood loss, surgery duration in the mild and severe CKD group. The 3-year overall survival rates for the severe CKD, mild CKD, and control groups were 48.6, 80.9, and 85.0 %, respectively, indicating significant differences between the severe CKD group and other two groups., Conclusions: Patients with severe CKD show an increased risk of morbidity and mortality following gastrectomy, and their prognosis is usually poor. Studies with a large cohort are essential to refine the risk stratification for gastrectomy in this high-risk population.

Objectives: The purpose of this study was to determine the survival benefit of bursectomy by retrospectively comparing the prognosis in patients undergoing D2 lymphadenectomy and gastrectomy (D2 gastrectomy) with bursectomy for gastric cancer with that in patients undergoing D2 gastrectomy alone., Methods: A total of 254 consecutive stage IA to IIIC gastric cancer patients undergoing curative intent surgery between 2004 and 2009 were enrolled. The patients were divided into 2 groups: a bursectomy group, which included patients undergoing curative D2 gastrectomy with bursectomy by one surgeon, and a nonbursectomy group, which included those undergoing curative D2 gastrectomy alone by other surgeons., Results: No statistically significant difference was observed in the number of metastatic nodes or penetration of the serosa between the 2 groups. The overall incidence of surgery-related complications was 24.0% in the bursectomy group (29 of 121 patients) and 25.6% in the nonbursectomy group (34 of 133 patients). The 5-year overall survival rate was 85.8% in the bursectomy group and 80.8% in the nonbursectomy group (hazard ratio 0.82; 95% confidence interval, 0.37-1.74; P=0.60)., Conclusions: The results of this retrospective study indicate no survival benefit for bursectomy plus D2 gastrectomy over D2 gastrectomy alone.

Introduction: Paraneoplastic syndromes are disorders associated with clinical signs and symptoms caused by substances produced by malignant disease and are not directly related to the physical effects of a primary or metastatic tumor. We describe a patient with gastrointestinal stromal tumor of the stomach accompanied by nephrotic syndrome as paraneoplastic syndrome in whom symptomatic treatment was ineffective. Nephrotic syndrome caused by gastrointestinal stromal tumors is quite rare, and to the best of our knowledge this is the first time that such a case has been documented., Case Presentation: We describe a 69-year-old Asian woman with a gastrointestinal stromal tumor of the stomach accompanied by paraneoplastic syndrome. The patient had severe hypoalbuminemia and proteinuria, which were apparently attributed to a gastrointestinal stromal tumor. After preoperative treatment for hypoalbuminemia, the tumor was resected and nephrotic syndrome improved. Two years after her operation, she is still alive with neither tumor recurrence nor nephrotic syndrome., Conclusion: Patients with refractory nephrotic syndrome caused by a malignant tumor should be treated aggressively, even if they are in poor general condition. Otherwise, the opportunity for potentially curative surgery may be missed.

A 70-year-old man with a gastric lesion was referred to our hospital because of an unusual pedunculated lesion in the gastric body. Endoscopic ultrasound showed scattered cystic lesions within a heterogeneous area confined to the submucosal layer. Endoscopic mucosal resection was performed to obtain a precise diagnosis, as well as for removal. The lesion was histopathologically diagnosed as a heterotopic submucosal gland. We herein describe this rare type of gastric polyp and provide a literature review.

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction., (© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Background: The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents., Methods: The analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated., Results: Positive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754)., Conclusion: The high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

The need for cardiac surgery among patients undergoing treatment for advanced digestive cancer is limited to the following situations:(i) heart diseases that can be life threatening if left untreated and that cannot be cured by medicinal treatment alone (e.g., cardiac tumors) and (ii) heart diseases (e.g., infectious endocarditis and pulmonary thromboembolism) occurring after digestive cancer surgery that need emergency treatment and that are resistant to medicinal treatment. We encountered 2 cases that required cardiac surgery.( Case 1) A 68-year-old woman with advanced gastric carcinoma accompanied by pyloric stenosis and left atrial myxoma underwent radical surgery for gastric cancer( Stage IIIA). Subsequently, the left atrial myxoma was resected before adjuvant chemotherapy for the treatment of gastric cancer was administered. One month after the surgery, multiple liver metastases appeared. However, they disappeared after chemotherapy was completed, and the patient survived for more than 3 years with complete response. (Case 2) A 67-year-old woman who underwent a Hartmann operation for obstructive rectal cancer (Stage II) experienced infectious endocarditis after the surgery. Because the endocarditis was resistant to medicinal treatment and acute heart failure was anticipated, cardiac surgery was performed. Approximately 2 months after the surgery, the bacilli( methicillin-resistant Staphylococcus aureus [MRSA]) were not found in blood culture. However, multiple liver metastases appeared immediately after the disappearance of the bacilli, and the patient died 3 months after the surgery. In both cases, cancer recurrence occurred early after cardiac surgery. Excessive surgical stress due to cardiac surgery may have promoted cancer recurrence. A decision pertaining to the timing of cardiac surgery is difficult in cases of patients with advanced digestive cancer and co-existing heart disease, which cannot be cured by medicinal treatment.

Purpose: The aim of this study was to investigate the impact of the prognostic nutritional index (PNI) on the long-term outcomes in gastric cancer patients., Methods: This study reviewed the medical records of 548 patients with gastric cancer who underwent gastrectomy. The PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PNI. The multivariate analysis was performed to identify the prognostic factors., Results: The mean PNI was significantly lower in patients with T3-T4 tumors (P < 0.001) and lymph node metastasis (P < 0.001) than in those without such factors. Patients who had a postoperative complication had a lower mean PNI than those without (P = 0.023). When the ROC curve analysis was performed, the optimal cutoff value of the PNI for predicting the 5-year survival was 48. In the multivariate analysis, a low PNI was an independent predictor for poor overall survival (P < 0.001). In the subgroup analysis, the overall and relapse-free survival rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III disease., Conclusions: The PNI is a simple and useful marker for predicting the long-term outcomes of gastric cancer patients independent of the tumor stage. Based on our results, we suggest that the PNI should be included in the routine assessment of gastric cancer patients.

Memory T cells survive for months and even years and are critical for host defense in humans. They have been recently suggested to play a significant role in tumor immunity. In this study, we aimed to investigate the clinical impact of tumor-infiltrating memory T cells on human gastric cancer. We evaluated CD45RO(+)T cells infiltrating into primary gastric cancer tissues by immunohistochemistry in 101 patients with gastric cancer. Patients were classified into 2 groups (CD45RO(+Hi) and CD45RO(+Lo)) based on the number of positively stained T cells. There was no significant correlation observed between CD45RO status and post-operative prognosis in early gastric cancer. By contrast, in advanced cancer, the post-operative overall and disease-free survival of patients with CD45RO(+Hi) were significantly improved compared to those of patients with CD45RO(+Lo). In addition, CD45RO status in the primary tumors significantly correlated with the development of post-operative recurrence, particularly peritoneal recurrence. Furthermore, the local expression of interferon-γ (IFN-γ) in the CD45RO(+Hi) tumors was significantly higher than that in the CD45RO(+Lo) tumors, suggesting that CD45RO(+) T cells induced local immune activation. Multivariate analysis indicated that the CD45RO(+) status was an independent prognostic factor in advanced gastric cancer. In conclusion, tumor-infiltrating CD45RO(+) memory T cells are functional and have significant prognostic value in human gastric cancer. Our data suggest that adaptive immune response is clinically critical in gastric cancer.

Purpose: The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer., Methods: Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry., Results: A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%., Conclusions: Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.

Purpose: The purpose of this study was to investigate whether intravenous (i.v.) administration allowed docetaxel to penetrate ascites in gastric cancer patients with peritoneal dissemination., Patients and Methods: Twelve patients with disseminated gastric carcinoma were enrolled in the study. All patients received docetaxel-containing drug regimens: i.v. administration of 40 mg/m(2) docetaxel in 6 patients, and 60 mg/m(2) in the remainder. Docetaxel concentrations in the plasma and ascites were measured., Results: Docetaxel was detected in the ascites of 4 patients in the 40 mg/m(2) group and 5 patients in the 60 mg/m(2) group. The highest concentration of docetaxel in plasma was detected at immediately after administration (median: 1,660 ng/mL, 501-2,560 ng/mL), after which it gradually decreased. The highest concentration of docetaxel in ascites was observed at ~7 h after administration and varied among cases (median: 18 ng/mL, 11-52 ng/mL)., Conclusion: Intravenous administration allows to penetrate ascites in gastric cancer patients with peritoneal dissemination.