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In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs., (© 2024. The Author(s).)

Background: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial., Methods: The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group., Results: The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020-0.923), significantly less with LCI than with WLI., Conclusion: The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication., (© 2024 John Wiley & Sons Ltd.)

Introduction: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC., Methods: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines., Result: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells., Conclusion: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype., (© 2023 S. Karger AG, Basel.)

Introduction: Severe and extensive gastric atrophy, extensive or incomplete gastric intestinal metaplasia, and gastric dysplasia are considered high-risk gastric precancerous lesions (HGPLs). Endoscopic findings based on the endoscopic Kyoto classification (EKC) and the Kimura-Takemoto classification (KTC) have been reported to be significantly associated with HGPLs. This study aimed to compare these two classifications in predicting active Helicobacter pylori (H. pylori) infection and HGPLs., Methods: This is a cross-sectional study conducted on naïve dyspeptic patients who underwent upper gastrointestinal endoscopy at a tertiary hospital. Endoscopic findings were scored according to the EKC and KTC. Mapping biopsies were taken, and H. pylori infection was determined using a locally validated rapid urease test and histology. The performance of EKC was compared with that of KTC using the area under the receiver operating characteristic curve (AUC) in predicting active H. pylori infection and HGPLs., Results: There were 292 patients with a median age of 46 and a male-to-female ratio of 1:1. The rates of active H. pylori infection and HGPLs were 61.3% and 14.0%, respectively. The EKC was better than the KTC in predicting active H. pylori infection (AUC: 0.771 vs. 0.658, respectively; p < 0.001). However, these two classifications had comparable performance in predicting HGPLs (AUC: 0.792 vs. 0.791, respectively; p = 0.956)., Conclusion: Compared to EKC, KTC is inferior in predicting active H. pylori infection but has comparable performance in predicting HGPLs., (© 2024 S. Karger AG, Basel.)

Background: Non-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development., Materials and Methods: Formalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer., Results: NHPH infection rates were 4/21 (19%) in "Hp current" patients, 4/37 (11%) in "Hp previous" infection patients, and 1/15 (7%) in "Hp naïve" patients, showing no significant difference in infection rates based on Hp infection status. NHPH infection rates in gastric cancer patients were similar to those in the patients with gastritis-related diseases reported in the previous study. A comparison of NHPH-positive and negative patients showed no significant differences in atrophic gastritis status, serum gastritis markers, or clinicopathological characteristics of gastric cancer, such as localization, size, gross type, differentiation, or depth., Conclusions: The association between gastric cancer and NHPH infection would have important implications for gastric cancer prevention, diagnostics, and treatment, however, no significant association was found in this particular population., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to be declared for any of the authors., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

We present a rare case that showed the coexistence of gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma in Helicobacter pylori-naive stomach. A 72-year-old man was followed up after surgery for epithelial carcinoma of the glottis at the Department of Otolaryngology. He underwent an upper gastrointestinal endoscopy for an abnormal PET-CT accumulation, which revealed gastric adenocarcinoma of fundic gland type in the gastric fundus and MALT lymphoma in the upper gastric body. Hence, we performed an endoscopic submucosal dissection for gastric cancer and diagnosed gastric adenocarcinoma of fundic gland type derived from a hamartomatous-inverted polyp. Subsequently, Gastric MALT lymphoma was treated with radiation therapy because the API2-MALT1 gene was positive and the Helicobacter pylori infection was negative. A complete response was observed. Even in Hp-naive stomachs, cases such as the present case are complicated by special types of gastric cancer and MALT lymphoma, and endoscopic examination should be performed with these diseases in mind., (© 2023. Japanese Society of Gastroenterology.)

Background: The transorally inserted anvil (OrVil™) is frequently selected for esophagojejunostomy after laparoscopic total gastrectomy (LTG) because of its versatility. During anastomosis with OrVil™, the double stapling technique (DST) or hemi-double stapling technique (HDST) can be selected by overlapping the linear stapler and the circular stapler. However, no studies have reported the differences between the methods and their clinical significance., Methods: A randomized controlled clinical trial with a parallel assignment and single-blind outcomes assessment analysis was conducted. Patients with gastric cancer eligible for LTG who met the selection criteria were randomized. Preoperative characteristics and perioperative and postoperative outcomes were compared between the DST and HDST. The primary endpoint was an anastomosis-related complication, and the secondary endpoints were perioperative outcomes and postoperative complications, excluding anastomosis-related complications., Results: Thirty patients with gastric cancer were eligible and randomized. LTG and esophagojejunostomy were successfully performed in all patients, without conversion to laparotomy. Preoperative characteristics, excluding preoperative chemotherapy, were not significantly different between the two groups. One anastomotic leakage of Clavien-Dindo classification grade ≥ IIIa was observed in the DST, although no significant difference was found between the two groups (6.6% vs. 0%, P = 0.30). In the HDST, one case of anastomotic stricture required endoscopic balloon dilation. No significant differences were found in operative time, whereas the anastomosis time was significantly shorter in the HDST than in the DST (47.5 ± 15.8 vs. 38.2 ± 8.8 min, P = 0.028). Except for anastomosis-related complications, postoperative complications (P = 0.282) and postoperative hospital stay for the DST and HDST were not significantly different., Conclusions: No superiority was found between the DST and HDST with OrVil™ in esophagojejunostomy of LTG for gastric cancer with respect to postoperative complications, whereas the HDST may be preferable in terms of the simplicity of the surgical technique., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis., Methods: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group., Results: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80., Conclusion: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future., (© 2023. The Author(s).)

Background and Aim: The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI)., Methods: The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI., Results: A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI., Conclusion: Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Gastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development., Methods: We enrolled 22,736 patients aged 20-95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger-Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling. First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up., Results: Among the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer., Conclusions: The combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer., (© 2022. The Author(s).)

Background: We have previously reported that eradication therapy was more effective against Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma in non-Helicobacter pylori Helicobacter (NHPH)-positive cases than in NHPH-negative cases and that the infection status of NHPH could be a predictive marker for the efficacy of eradication therapy for H. pylori negative gastric MALT lymphoma. However, a diagnostic test for NHPH infection has not yet been clinically established. In this study, we investigated the endoscopic findings in cases of H. suis-infected gastritis associated with gastric MALT lymphoma reported at our institution., Materials and Methods: Participants were selected from cases of gastric MALT lymphoma who underwent esophagogastroduodenoscopy at Hiroshima University Hospital, who were negative for the API2-MALT1 gene, and who received eradication therapy as a first-line treatment. We examined the endoscopic findings in nine cases from this group in which H. suis infection was confirmed by polymerase chain reaction., Results: Endoscopic findings, such as cracked mucosa, spotty redness, nodular gastritis-like appearance, and white marbled appearance, which have been reported as characteristics of NHPH gastritis, were observed in multiple cases. The most common endoscopic findings in this study were cracked mucosa (7/9 cases), followed by spotty redness (6/9 cases), nodular gastritis-like appearance (5/9 cases), and white marbled appearance (2/9 cases)., Conclusions: Our study may serve as a reference for re-evaluation of the diagnostic criteria for H. suis infection and indications for eradication therapy, particularly for cases of H. pylori negative gastric MALT lymphoma, where endoscopic findings such as those seen in this study were observed in the background mucosa., (© 2022 John Wiley & Sons Ltd.)

Background: Eradication therapy is known to be effective against Helicobacter pylori-positive gastric MALT lymphoma but predicting the efficacy of eradication therapy against Helicobacter pylori-negative gastric MALT lymphoma is difficult. Recent reports have shown that non-Helicobacter pylori helicobacter infections induce gastric MALT lymphoma, and we aimed to clarify whether non-Helicobacter pylori helicobacter infections are associated with the efficacy of eradication therapy., Methods: We analyzed eradication therapy as a first-line treatment for 182 cases of gastric MALT lymphoma, classified according to Helicobacter pylori infection and API2-MALT1 mutation status. We also evaluated the non-Helicobacter pylori helicobacter infection status in 29 Helicobacter pylori-negative cases via PCR with DNA extracted from paraffin-embedded biopsy tissues. Finally, we analyzed the relationship between non-Helicobacter pylori helicobacter infection status and eradication therapy outcome., Results: The API2-MALT1 mutation was observed in 13/182 patients (7.1%), none of whom were cured by eradication therapy. Helicobacter pylori-negative cases had a significantly higher non-Helicobacter pylori helicobacter infection rate than Helicobacter pylori-positive cases (16/29, 55% vs. 3/29, 10%; P < 0.05). Among the Helicobacter pylori-negative cases, non-Helicobacter pylori helicobacter-positive cases had a significantly higher complete response rate than non-Helicobacter pylori helicobacter-negative cases (12/16, 75% vs. 3/13, 23%; P < 0.05)., Conclusion: Helicobacter pylori-negative and API2-MALT1-negative gastric MALT lymphoma cases exhibited a high rate of non-Helicobacter pylori helicobacter infections, which may have contributed to the success of eradication therapy. Therefore, we recommend eradication therapy as a first-line treatment for non-Helicobacter pylori helicobacter-positive gastric MALT lymphoma.

Submucosal deep invasion of gastric cancer (T1b2; depth of submucosal invasion ≥ 500 μm) is a risk factor for lymph node metastasis and, thus, is one of the criteria for curative treatment. Our aim was to evaluate the specific influence of endoscopic submucosal dissection (ESD) on the prognosis of patients with T1b2 gastric cancer. This was a retrospective analysis of 248 consecutive patients, with 252 pT1b2 gastric cancer lesions, who underwent ESD prior to additional surgery (Group A, n = 101) or surgery only (Group B, n = 147). After propensity score-matching (for sex, age, tumor diameter and gross type), we compared pathological characteristics between the 2 groups and the prognosis over a follow-up period ≥ 60 months. Compared to Group B, patients in Group A were older, with a higher proportion of men. The proportion of depressed and undifferentiated type tumors was greater in Group B than A, with larger tumor size and depth of submucosal invasion as well. There was no incidence of local recurrence, but distant metastasis was identified in 5% of cases in Group A and 3% in Group B. After propensity score-matching, there were no difference in the 5-year overall survival rate between Group A and B (87.5% vs. 91.2%, respectively), nor in the 5-year disease-specific survival rate (96.3% vs. 96.4%, respectively). ESD prior to surgery for T1b2 gastric cancer did not adversely affect clinical outcomes after additional surgery.

Background and Aims: Linked color imaging (LCI) improved the visibility of gastric cancer and colorectal flat lesions. This study aimed to investigate the usefulness of LCI in detecting superficial esophageal squamous cell carcinomas (SESCC)., Methods: We enrolled 37 consecutive SESCC patients (46 SESCCs) diagnosed using LCI and blue laser imaging bright mode (BLI-BRT) and treated in Hiroshima University Hospital between April 2018 and November 2018. Eight professional endoscopists compared images obtained on non-magnifying BLI-BRT and LCI versus conventional white light imaging (WLI). Identification and boundary diagnosis of SESCC with LCI and BLI-BRT were compared with WLI. Changes in lesion visibility were clarified. Interobserver agreement was assessed. Clinicopathological features of lesion that influence visibility with LCI were assessed., Results: In LCI, 37% (17/46) of cases had improved visibility and 63% (29/46) had unchanged visibility (interobserver agreement = 0.74). Among cases with multiple lugol voiding lesions (LVLs), ΔE between the lesion and background mucosa was significantly higher in LCI than in WLI (20.8 ± 7.9 vs 9.2 ± 6.1, P < 0.05). No significant differences were found in tumor size, morphological type, color, depth, and smoking or drinking history. However, multiple LVLs were significantly higher among cases with improved versus unchanged visibility. On BLI-BRT, 39% (18/46) of cases had improved visibility and 61% (28/46) had unchanged visibility (interobserver agreement = 0.60)., Conclusion: Almost the same as BLI-BRT, LCI improves SESCC visibility compared with WLI. This is useful for cases with multiple LVLs. In cases without background coloration (BGC), LCI may make SESCC more visible than BLI-BRT.

Background and Aim: Endoscopic ultrasonography is a reliable diagnostic modality for determining indications of endoscopic submucosal dissection for early gastric cancer. We aimed to clarify the clinical significance of endoscopic ultrasonography in the invasion depth diagnosis of early gastric cancer., Methods: We retrospectively assessed 1598 consecutive patients with 2001 early gastric cancers who underwent EUS before ESD or surgery between October 2010 and April 2019 at our institution. Lesions were classified according to endoscopic ultrasonography-determined invasion depth as EUS-M/SM1 (lesions confined to sonographic layers 1 and 2 or lesions with changes in sonographic layer 3; depth, < 1 mm) and EUS-SM2 (lesions with changes in sonographic layer 3; depth, ≥ 1 mm). We evaluated the invasion depth determination accuracy of endoscopic ultrasonography and analyzed the clinicopathological features of misdiagnosed early gastric cancer cases., Results: The invasion depth determination accuracy was as follows: EUS-M/SM1: pathological T1a/T1b1 early gastric cancer, 97%; EUS-SM2: pathological T1b2 early gastric cancer, 79%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 95%, 98%, 69%, 97%, and 79%, respectively. In EUS-M/SM1 early gastric cancer, tumor size of ≥ 15 mm, presence of ulceration, and undifferentiated histological type were significantly associated with endoscopic ultrasonography accuracy. In EUS-SM2 early gastric cancer, tumor size of ≥ 30 mm was significantly associated with endoscopic ultrasonography accuracy., Conclusions: Endoscopic ultrasonography is a useful modality in accurately determining the invasion depth of early gastric cancer before endoscopic submucosal dissection.

Background: Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients., Methods: Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing., Results: H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples., Conclusions: Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Introduction: A transorally inserted anvil has been developed to facilitate the creation of a stapled anastomosis without the need for a purse string to secure the anvil into place during laparoscopic total gastrectomy (LTG). We describe a hemi-double stapling technique and application of a transorally inserted anvil for esophagojejunostomy during LTG, and we report the results of a retrospective study in which we examined the feasibility and safety of this method. We also describe the key technical details of the method., Methods: Our anastomotic method has four chief features: (a) the esophagus is cut at a slant, and its left cut end is cut and punched for the hemi-double stapling technique; (b) the anvil and circular stapler are connected, placing the distal jejunum in cranial traction; (c) a single layer of sutures is used to correct dog-earing and overlapping, and these points are completely closed with Lembert sutures; and (d) the jejunal limb is fixed to the duodenal stump to prevent kinking of the jejunal limb and to decrease tension on the anastomosis., Results: This method has been used in 53 patients thus far. LTG with Roux-en-Y reconstruction was successful in all patients, and there was no need for conversion to open surgery. The mean operative time was 313 minutes, and the mean blood loss was 106 mL. The mean postoperative hospital stay was 18 days. There was no anastomotic leakage or stenosis., Conclusion: Hemi-double stapling technique with a transorally inserted anvil for LTG can be performed safely and easily and safely. It can also product good outcomes., (© 2019 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Background: There is a lack of data regarding the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) without curative resection, and the relationship of these outcomes with hospital volumes remains unclear. This study evaluated long-term outcomes of patients who underwent ESD for EGC without curative resection according to hospital volumes in Japan., Methods: This multicenter retrospective study evaluated 1,969 patients who did not meet the criteria of the Japanese Gastric Cancer Association for curative resection between January 2000 and August 2011. Hospitals were classified according to the annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). Clinicopathological features, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared across groups after a generalized propensity score matching analysis., Results: In 495 pairs of generalized propensity score-matched patients, the 5-year OS, DSS, and RFS rates were 81.5%, 97.9%, and 97.6% for LMVG; 86.9%, 98.2%, and 97.0% for HVG; and 85.4%, 98.5%, and 97.6% for VHVG, respectively. The 5-year DSS and RFS rates did not significantly differ among the three groups. However, 5-year OS was significantly worse in the LMVG than in the HVG and VHVG (P < 0.001 and P = 0.008, respectively)., Conclusions: DSS and RFS in patients with EGC who did not meet the criteria for curative resection did not differ across hospital volumes in Japan. Even in cases in which ESD for EGC involved non-curative resection, the procedure is feasible across Japanese hospitals with different volumes.

Background and Aim: The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan., Methods: We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA., Results: Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P < 0.01). Twenty-two (6.4%) patients, including two with submucosal invasion, were negative for H. pylori and had mucosal SRCC component in the cancer lesions. Of the 259 SRCC cases (pure SRCC or SRCC + PDA), H. pylori-uninfected cases had different clinicopathological characteristics compared with H. pylori-positive cases. Particularly, the ratio of patients with submucosal invasive SRCC was significantly lower in the H. pylori-uninfected gastric cancer group than in those with H. pylori infection., Conclusion: Helicobacter pylori-uninfected gastric cancer is not rare among pure DGC patients in Japan. SRCC in patients without H. pylori infection is less likely to be invasive., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM)., Objective: This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC., Methods: This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients., Results: The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p < 0.001) and vascular invasion (HR 4.75; p = 0.014). Moreover, patients with both LNM and vascular invasion had a high rate of recurrence after additional surgery (24.6% in 5 years), with a high HR (119.32) compared with those with neither LNM nor vascular invasion. Among patients with no vascular invasion, a high rate of recurrence was observed in those with N2/N3 disease according to the American Joint Committee on Cancer TNM staging system (27.3% in 5 years), in contrast with no recurrence in those with N1 disease., Conclusions: Patients with both LNM (N1-N3) and vascular invasion, as well as those with N2/N3 disease but no vascular invasion, would be candidates for adjuvant chemotherapy after additional surgery for curability C-2 ESD of EGC.

Background/aim: The benefits of gastrectomy for elderly gastric cancer (GC) patients remain unknown. The aim of this study was to evaluate the validity of gastrectomy., Patients and Methods: Patients who had R0 or R1 resection and diagnosed as pathological Stage I-III GC were enrolled in this study. Patients were classified according to age: Elderly group (≥80 years old), non-Elderly group (70-79 years old), Standard group (≤69 years old)., Results: As the age raised, the number of comorbidities increased and patients had a worse physical status. Operative procedure and postoperative complications of the Elderly group were similar to that of the non-Elderly group. The overall survival was similar in pathological Stages I and III between the Elderly and non-Elderly groups, while the Stage II Elderly group had shorter overall survival. Also, the Elderly group did not undergo adjuvant chemotherapy compared to other groups., Conclusion: Gastrectomy can be performed safely in elderly patients following gastrectomy, survival of elderly patients was similar to non-elderly patients. Therefore, gastrectomy is an acceptable treatment for elderly patients in good condition., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 68-year-old female patient presented with advanced gastric cancer and multiple hepatic tumors. Upper GI endoscopy showed a type 3 lesion in the posterior wall of the gastric body. Abdominal computed tomography revealed multiple liver metastases, and staging laparoscopy identified peritoneal dissemination. She was diagnosed with clinical Stage Ⅳ gastric cancer(cT3N2M1H1). She received 3 courses of combined chemotherapy containing S-1 and cisplatin. The therapeutic response was PR. We performed total gastrectomy with D2 lymph node dissection and splenectomy. Histopathological examination revealed no residual cancer cells, indicating pCR. She continued S-1 adjuvant chemotherapy and has remained free from recurrence for 18 months.

Background and Aims: Cancer recurrence is observed in some patients without additional radical surgery after endoscopic submucosal dissection (ESD) that does not fulfill the curability criteria for early gastric cancer (EGC), categorized as "noncurative resection" or "curability C-2" in the guidelines. However, time to cancer recurrence is different in such patients. Thus, we aimed to identify the risk factors of early and late cancer recurrences in these patients., Methods: Between 2000 and 2011, this multicenter study analyzed 905 patients who were followed up without additional radical surgery after ESD for EGC categorized as curability C-2. We evaluated the risk factors for early and late cancer recurrences, separately, after ESD. The cut-off value was defined at 2 years., Results: Time to cancer recurrence in the enrolled patients showed a bimodal pattern, and the 5-year cancer recurrence rate was 3.2%. Multivariate Cox analyses revealed that lymphatic invasion (hazard ratio [HR], 8.56; P = .003) was the sole independent risk factor for early cancer recurrence. Regarding late cancer recurrence, vascular invasion (HR, 4.50; P = .039) was an independent risk factor, and lymphatic invasion tended to be a risk factor (HR, 3.63; P = .069)., Conclusions: This multicenter study with a large cohort demonstrated that lymphatic invasion is mainly associated with early cancer recurrence; however, vascular invasion was a risk factor only for late recurrence in patients without additional treatment after ESD for EGC categorized as curability C-2. This finding may contribute to decision making for treatment strategies after ESD, especially for patients with a relatively short life expectancy., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study., Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients., Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively., Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases., (© 2018 S. Karger AG, Basel.)

Background: Billroth Ⅰ (BⅠ) reconstruction and Roux-en-Y (RY) reconstruction are both commonly performed after distal gastrectomy (DG). We conducted a retrospective study to evaluate which is the better option., Methods: Included in our study were 162 patients who, between April 2011 and October 2015, underwent DG followed by BⅠ reconstruction (n = 93) or RY reconstruction (n = 69). All patients were followed up for at least 1 year. We compared perioperative outcomes, postoperative complications, gastrointestinal (GI) symptoms, endoscopic findings, and nutritional status between the 2 groups of patients., Results: Patient characteristics did not differ between the 2 groups, with the exception of the incidence of gastric body tumors, which was significantly higher in the RY group (73.9% vs. 19.4%; p < 0.001). Operation time was significantly longer in the RY reconstruction group (p < 0.001). There was no significant between-group difference in the grades of GI dysfunction (p = 0.122).The endoscopically determined RGB (Residual food, Gastritis, Bile reflux)scores were significantly better in the RY reconstruction group than in the BI reconstruction group (p = 0.027, p < 0.001,p < 0.001,respectively).There was also no significant between-group difference in the change (1-year postoperative value/preoperative value) in body weight, body mass index, serum albumin concentration, or total cholesterol concentration (p = 0.484,p = 0.613,p = 0.760,p = 0.890, respectively)., Conclusions: RY reconstruction appears not to be advantageous over BⅠ reconstruction in terms of GI function or nutritional status 1 year after surgery. RY reconstruction does appear to be superior in terms of preventing bile reflux but takes more operation time., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: Additional surgery is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer due to the risk of lymph node metastasis. However, age may affect the clinical management of these patients., Objectives: The aim of our retrospective multicenter study was to clarify whether age affects decision-making after noncurative ESD and if the decision affects long-term outcomes., Methods: Age was classified as follows: non-elderly, <70 years (n = 811); elderly, 70-79 years (n= 760); and super-elderly, ≥80 years (n = 398). Age associations with the selection for additional surgery were evaluated using logistic regression analysis. Long-term outcomes were also evaluated in each age group., Results: Age was inversely related to the rate of additional surgery, which ranged from 70.0% in the non-elderly group to 20.1% in the super-elderly group (p < 0.001). On multivariate analysis, age <70 years (versus age ≥80 years) was associated with the -selection of additional surgery (OR 18.6). Overall survival (OS) in patients who underwent additional surgery was -significantly higher in the non-elderly and elderly groups (p< 0.001), whereas the difference was not significant in the super-elderly group (p = 0.23)., Conclusions: Despite the fact that almost 80% of super-elderly patients did not undergo additional surgery, the difference of OS between patients with and without additional surgery was not significant only in patients ≥80 years. Therefore, establishment of criteria for selecting treatment methods after noncurative ESD in elderly patients is required., (© 2019 S. Karger AG, Basel.)

Background: Billroth I reconstruction is a means of anastomosis that is widely performed after surgical resection for distal gastric cancer. Interest has grown in totally laparoscopic gastrectomy, and several methods for totally laparoscopic performance of Billroth I reconstruction have been reported. However, the methods are cumbersome, and postoperative complications such as twisting at the site of anastomosis and obstruction due to stenosis have arisen. We developed an augmented rectangle technique (ART) by which the anastomosis is created laparoscopically with the use of three automatic endoscopic linear staplers, and the resulting anastomotic opening is wide and less likely to become twisted or stenosed. The technical details of our ART-based Billroth I anastomosis are presented herein along with results of the procedure to date., Methods: The technique was applied in 160 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer between December 2013 and August 2017. Clinicopathological data, surgical data, and postoperative outcomes were analyzed., Results: During surgery, there were no troubles associated with gastrointestinal reconstruction and there was no transition to laparotomy. There were no postoperative complications, including suture failure and stenosis, associated with the gastrointestinal reconstruction, and the average postoperative hospital stay was 12 days., Conclusion: Totally laparoscopic ART-based Billroth I reconstruction is both feasible and safe. We expect this technique to contribute to the spread of safe totally laparoscopic surgery for gastric cancer.

Background: Although bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains problematic, especially in patients taking anticoagulants, there are differing views on the ideal and optimal management for these patients. This study investigated the risk of bleeding after ESD in patients taking anticoagulants., Methods: We enrolled 61 consecutive patients taking anticoagulants (anticoagulant group) and 968 patients taking no antithrombotic agents (non-antithrombotic group) treated with ESD for EGC between December 2010 and October 2016. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors., Results: Incidences of bleeding after ESD were significantly higher (14%; 11/76) in the anticoagulant group compared to the non-antithrombotic group (3%; 40/1,167). Moreover, bleeding after ESD was significantly more common in patients in the warfarin monotherapy group (14%; 5/37) and in the direct oral anticoagulant (DOAC) monotherapy group (22%; 4/18), compared to the non-antithrombotic group. Multivariate analysis revealed that dialysis, the use of anticoagulants, and an operation time ≥75 min were independent risk factors for bleeding after ESD., Conclusions: Our data suggest that patients who take warfarin and receive heparin bridging, and those who take DOAC medication, are prone to bleeding after ESD for EGC., (© 2018 S. Karger AG, Basel.)

Background: Blue laser imaging (BLI) and linked color imaging (LCI) are the color enhancement features of the LASEREO endoscopic system, which provide a narrow band light observation function and expansion and reduction of the color information, respectively., Methods: We examined 82 patients with early gastric cancer (EGC) diagnosed between April 2014 and August 2015. Five expert and 5 non-expert endoscopists retrospectively compared images obtained on non-magnifying BLI bright mode (BLI-BRT) and LCI with those obtained via conventional white light imaging (WLI). Interobserver agreement was also assessed., Results: In experts' evaluation of the images, an improvement in visibility was observed in 73% (60/82) and 20% (16/82) of cases under LCI and BLI-BRT, respectively. In non-experts' evaluation of the images, an improvement in visibility was observed in 76.8% (63/82) and 24.3% (20/82) of cases under LCI and BLI-BRT, respectively. There were no significant differences between experts and non-experts in the evaluation of the images. The improvement in visibility was significantly higher with LCI than with BLI-BRT in experts and non-experts (p < 0.01). With regard to tumor color on WLI, the improvement in the visibility of reddish and whitish tumors was significantly higher than that of isochromatic tumors when LCI was used. The improvement in visibility with LCI was observed in 71% (12/17) and 74% (48/65) of patients with and without Helicobacter pylori (Hp) eradication, respectively; no significant difference in improvement was observed between these groups. The interobserver agreement was good to satisfactory at ≥ 0.62., Conclusions: In conclusion, our study showed that LCI improved the visibility of EGC, regardless of the level of endoscopists' experience or Hp eradication in patients, particularly for EGCs with a reddish or whitish color. The improvement in visibility was significantly higher with LCI than that with BLI.

Background: ESD allows higher rates of en-bloc and R0 resections, but has occasionally complications such as aspiration pneumonia. Factors associated with aspiration pneumonia are not completely understood., Aims: To analyze the relationship between aspiration pneumonia and preoperative factors including pulmonary function tests., Methods: A total of 978 patients with gastric tumors who had received pulmonary function tests were treated by ESD between June 2006 and May 2014. Pulmonary function tests were assessed using a spirometer. The patients were categorized into four groups according to the predicted vital capacity (%VC) and forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1.0%): normal; restrictive pulmonary dysfunction; obstructive; and mixed. The factors associated with aspiration pneumonia were retrospectively analyzed., Results: Among the 268 cases with abnormal pulmonary function, 10 cases (3.7%) developed aspiration pneumonia. On the other hand, 7 cases (1.0%) with normal pulmonary function developed pneumonia. There was a significant correlation between pulmonary function and aspiration pneumonia (p = 0.010). When the pulmonary function cases were stratified into subgroups, 2.5% of cases with obstructive pulmonary dysfunction developed pneumonia, 5.5% with restrictive and 5.3% with mixed. By logistic regression analysis, pulmonary function, the presence of cerebral vascular disease, and procedure time were identified as significant independent risk factors associated with aspiration pneumonia. The odds ratios for pulmonary function, cerebral vascular disease, and procedure time were 3.6, 5.1, and 5.2, respectively., Conclusions: Preoperative pulmonary function tests may be useful markers to evaluate the risk for aspiration pneumonia after gastric ESD.

Background: No previous study has confirmed the safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the super-elderly patient population. The current study aimed to evaluate the validity of ESD for EGC in super-elderly patients aged ≥85 years with comorbidities., Methods: Our study group included 85 super-elderly patients (102 EGCs) who were diagnosed at Hiroshima University Hospital between April 2002 and October 2014. We evaluated the en bloc resection rates, R0 resection rates, complication rates, and prognosis in relation to the degree of comorbidities (group A-H, patients with high-risk comorbidities; group A-L, patients with low-risk comorbidities; group B, patients without comorbidities; and group C, patients followed without ESD)., Results: The en bloc resection rates were 100, 96, and 100 % in groups A-H, A-L, and B, respectively. R0 resection rates were 94, 96, and 94 % in groups A-H, A-L, and B, respectively. There were no severe complications related to ESD. During the follow-up period, there was a significantly higher frequency of death in group A than in group B (p < 0.01), and there were no significant differences between groups A-H and A-L. However, there were no cases of death related to gastric cancer., Conclusions: ESD was performed safely, and death related to gastric cancer was prevented in super-elderly patients with comorbidities, regardless of the degree of the disease. However, patients with comorbidities are at a high risk of poor prognosis.

Background: Identifying a precise demarcation line (DL) is indispensable for pathological complete en bloc endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We evaluated the useful condition of chromoendoscopy with indigo carmine and acetic acid for marking dots around lesions before ESD for EGC., Methods: We examined 98 consecutive patients with 109 intramucosal EGCs (mean diameter, 17.8 ± 12.4 mm; main histologic type, 96 intestinal and 13 diffuse) resected by en bloc ESD after chromoendoscopy with indigo carmine and acetic acid between December 2012 and February 2014. The DL was identified by this technique just before ESD (mean chromoendoscopy observation time, 71.6 s); subsequently, marking dots were placed around the EGC. EGCs were classified into two groups: useful for identifying the DL or useless. Clinicopathological characteristics and clinical outcomes were evaluated in each group., Results: Forty-two of the 109 cases (38.5 %) were determined useful for chromoendoscopy with indigo carmine and acetic acid. Multivariate analysis with logistic regression showed that macroscopic type (protruded or flat elevated-type) and atrophic border (the oral side of tumor) were independently associated with the usefulness of chromoendoscopy using indigo carmine and acetic acid for identifying the DL of EGCs (P < 0.05). The histologically positive horizontal margin after ESD was 0 % (0/42) in useful cases, and 7.5 % (5/67) in useless cases., Conclusions: Before ESD, chromoendoscopy with indigo carmine and acetic acid can be used for creating precise markings in protruded or flat elevated-type EGC or at the atrophic border on the oral side of EGCs.

Background: Although endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), there is no consensus regarding the management of positive horizontal margin (HM) despite en bloc ESD. The aim of the current study was to identify the risk factors and optimal management of positive HM in EGCs resected by en bloc ESD., Methods: A total of 890 consecutive patients with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June 2011. Clinicopathological data were retrieved retrospectively to assess the positive HM rate, local recurrence rate, risk factors for positive HM, and outcomes of treatment for local recurrent tumor. Positive HM was defined as a margin with direct tumor invasion (type A), the presence of cancerous cells on either end of 2-mm-thick cut sections (type B), or an unclear tumor margin resulting from crush or burn damage (type C)., Results: The positive HM rate was 2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local recurrent tumors were intramucosal carcinomas, and were resected curatively by re-ESD. Multivariate analysis with logistic regression showed tumor location in the upper third of the stomach and lesions not matching the absolute indication to be independent risk factors for positive HM., Conclusion: The risk factors for HM positivity in cases of EGC resected by en bloc ESD are tumor location in the upper third of the stomach and dissatisfaction of the absolute indication for curative ESD.

Goals: To evaluate the usefulness of a newly devised computer system for use with laser-based endoscopy in differentiating between early gastric cancer, reddened lesions, and surrounding tissue., Background: Narrow-band imaging based on laser light illumination has come into recent use. We devised a support vector machine (SVM)-based analysis system to be used with the newly devised endoscopy system to quantitatively identify gastric cancer on images obtained by magnifying endoscopy with blue-laser imaging (BLI). We evaluated the usefulness of the computer system in combination with the new endoscopy system., Study: We evaluated the system as applied to 100 consecutive early gastric cancers in 95 patients examined by BLI magnification at Hiroshima University Hospital. We produced a set of images from the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened lesions; and surrounding tissues, and we attempted to identify gastric cancer, reddened lesions, and surrounding tissue quantitatively., Results: The average SVM output value was 0.846 ± 0.220 for cancerous lesions, 0.381 ± 0.349 for reddened lesions, and 0.219 ± 0.277 for surrounding tissue, with the SVM output value for cancerous lesions being significantly greater than that for reddened lesions or surrounding tissue. The average SVM output value for differentiated-type cancer was 0.840 ± 0.207 and for undifferentiated-type cancer was 0.865 ± 0.259., Conclusions: Although further development is needed, we conclude that our computer-based analysis system used with BLI will identify gastric cancers quantitatively.

We report a case of a large gastric gastrointestinal stromal tumor (GIST), which became resectable and achieved pathological complete response after neoadjuvant chemotherapy with imatinib mesylate. A 59-year-old man presented with left hypochondrial pain. Abdominal computed tomography (CT) revealed gastric GIST invading the spleen and the diaphragm. Administration of imatinib mesylate was initiated as neoadjuvant chemotherapy. Six months after neoadjuvant chemotherapy with imatinib mesylate, abdominal CT revealed a reduction in tumor size. We judged the tumor resectable and performed partial gastrectomy and splenectomy. Histologically, number of myofibroblasts increased, but no viable tumor cells were observed. Pathological complete response was obtained.

Background: The incidence of gastric cancer after successful Helicobacter pylori eradication has been increasing. We previously reported that epithelium with low-grade atypia (ELA) appeared on the surface of gastric cancer after H. pylori eradication. Here, we investigate the clinical and biological characteristics of such ELA., Methods: We studied 27 cases of gastric cancer detected after successful H. pylori eradication therapy. We examined the prevalence of ELA among these cases and its significance for endoscopic discovery after H. pylori eradication. We additionally investigated the mucus, p53 and Ki67 expressions in ELA., Results: Epithelium with low-grade atypia that continuous with the gastric tumor was detected in 22 of 27 cases (81%), a significantly greater percentage than that for controls (p < 0.01). We found that gastric-type mucin was frequently expressed in this epithelium. Neither p53- nor Ki67-positive cells were found in ELA, irrespective of their expression in tumor tissue. The presence of ELA was positively correlated with the clinical interval between H. pylori eradication and gastric cancer detection., Conclusions: Epithelium with low-grade atypia on gastric cancer tissue, which may develop from gastric cancer cells, is frequently present after successful eradication therapy. This phenomenon could influence the practice of endoscopic diagnosis of gastric cancers., (© 2014 John Wiley & Sons Ltd.)

Background: Patients with negative anti-Helicobacter pylori antibody titer and high pepsinogen (PG) level (group A) are regarded as having a low risk for gastric cancer. However, gastric cancer cases are occasionally observed in this group. We aimed to elucidate the clinical features of gastric neoplasm in group A patients and reviewed advanced methods for mass screening., Materials and Methods: A total of 271 gastric epithelial neoplasm patients were enrolled. We classified them according to the H. pylori-PG system and determined the number of patients in each group. After excluding true H. pylori-negative cases from group A (group A'), we examined the differences between group A' and group non-A., Results: Group A included 30 (11%) patients, and only three of these were true negative for H. pylori. All patients in group A' (n = 27) exhibited endoscopic atrophy in the gastric corpus. Serologically, these patients showed low gastrin, low PG II and high PG I/II ratio, indicative of post-eradication. Histologically, 24 (89%) of these had little inflammation, and 26 (96%) were negative for H. pylori by immunohistochemistry. No difference was observed in the incidence of metachronous gastric tumors between group A' and group non-A. The discriminant function using gastrin and PGs could distinguish these 27 patients from true H. pylori-negative controls with 85% sensitivity and 84% specificity., Conclusions: Group A included a certain number of patients with atrophic gastritis who were potentially at risk of gastric neoplasm development. Although evaluation of corpus atrophy is necessary for the identification of these patients, the discriminant function may be useful., (© 2013 John Wiley & Sons Ltd.)

Background: According to the Japanese Gastric Cancer Treatment Guidelines, the expanded criteria for endoscopic resection (ER) of undifferentiated-type early gastric cancer (UEGC) is ulcer-negative, intramucosal cancer 20 mm or less in diameter without lymphovascular invasion. The aim of this study was to confirm validity of the expanded criteria for curative ER of UEGC., Methods: Subjects were 125 patients from whom 125 UEGCs were resected endoscopically between April 1990 and March 2011. Endoscopic mucosal resection (EMR) (28 lesions, 28 patients) or endoscopic submucosal dissection (ESD) (97 lesions, 97 patients) was performed. We determined the complete resection rate, post-ER bleeding rate, perforation rate, and outcome in both groups, and analyzed the survival outcomes of 84 patients who were followed for more than 5 years (mean, 101.9 months) according to the indication for ER [expanded criteria for curative (n = 52) vs. criteria for noncurative (n = 32)]., Results: Complete resection rates for EMR and ESD were 54 % (15 of 28) and 89 % (86 of 97), respectively, with that for ESD being significantly higher (p < 0.01). Outcomes after ER were as follows: among 52 cases of UEGC meeting the expanded criteria, additional surgical resection was performed in 11 cases of incomplete resection. No local recurrence or lymph node metastasis was observed. Forty-eight patients who were simply surveyed clinically (93.6 ± 38.4 months) after ER survived without recurrence; the remaining 7 patients died of other causes. Among the 32 cases of UEGC meeting the criteria for noncurative resection, additional surgical resection was performed in 13 cases. Among the 19 follow-up cases (108.3 ± 38.7 months), death due to metastasis of the primary disease occurred in 3 cases, death from other causes occurred in 5 cases, and local residual submucosal recurrence occurred in 1 case., Conclusions: ESD is a useful technique for complete resection as a total excisional biopsy compared with EMR and radical cure of UEGCs meeting the expanded criteria.

Background: Although recent guidelines for endoscopic submucosal dissection (ESD) as treatment for early gastric cancer (EGC) recommend noninterruption of low-dose aspirin (LDA) perioperatively, this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before to ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. Our purpose in this study was to confirm the validity of noninterrupted use of LDA in patients undergoing ESD for EGC., Methods: We studied 78 consecutive patients with 94 EGCs who were routinely taking LDA and were treated by ESD at Hiroshima University Hospital between April 2005 and June 2012. The patients were of two groups: those in whom LDA was interrupted perioperatively (53 patients with 66 EGCs) and those in whom LDA was continued perioperatively (25 patients with 28 EGCs)., Results: The complete resection rate was 92.4 % (61/66) in the LDA-interrupted group and 100 % (28/28) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after procedure were 10.6 % (7/66) and 4.8 % (3/66), respectively, in the LDA-interrupted group and 7.1 % (2/28) and 3.6 % (1/28) in the LDA-continued group. Two patients in the interrupted-LDA group suffered cerebrovascular infarction before ESD, and 2 patients in this group suffered acute myocardial infarction after ESD., Conclusions: Our data suggest that continued use of LDA does not increase the risk of bleeding during or after ESD for EGC and does decrease the risk of ischemic events.

Background and Aim: Endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), and the number of ESD performed for EGC in patients with chronic kidney disease (CKD) is increasing. Although patients undergoing hemodialysis tend to bleed and are at high risk for cardiovascular disease, the effectiveness and safety of ESD for EGC in patients with CKD in particular have not been established. The aim of this study was to evaluate the effectiveness and potential adverse effects of ESD for EGC in patients with CKD undergoing hemodialysis., Methods: Sixty-three consecutive CKD patients in whom 79 EGCs were treated by ESD between October 2004 and January 2012; 15 of the 63 patients were hemodialysis patients. Complete en bloc resection rate and ESD-related complications in hemodialysis patients versus non-hemodialysis patients were evaluated., Results: The complete en bloc resection rate was 100% (15/15) in the hemodialysis patients and 87.5% (56/64) in the non-hemodialysis patients, respectively. The post-ESD bleeding rate was 33% (5/15) and 9% (6/64), respectively (P < 0.05). Perforation occurred only in non-hemodialysis patients; the incidence was 5% (3/64). Two ESD-related deaths occurred among hemodialysis patients (13%, 2/15); femoral artery infarction triggered post-ESD bleeding in one of these two patients, and alveolar hemorrhage occurred in the other., Conclusion: Hemodialysis poses a risk of post-ESD bleeding. We must understand this risk and provide countermeasures for post-ESD bleeding in hemodialysis patients., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Whether submucosal fibrosis is related to ulceration and affects the outcome of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is unknown. This study aimed to determine ESD outcome in relationship to degree of submucosal fibrosis of gastric epithelial neoplasms and to identify factors predictive of submucosal fibrosis., Methods: Eight hundred ninety-one patients with 1,027 gastric epithelial neoplasms were treated by ESD from April 2005 to January 2011. Complete en bloc resection and perforation rates in relationship to degree of submucosal fibrosis (F0, no fibrosis; F1; mild fibrosis; F2, severe fibrosis) were determined during ESD, as well as degree of concordance between endoscopically observed ulceration and pathologically determined ulceration and pathological fibrosis stained with Masson's trichrome., Results: The complete en bloc resection rate was significantly low and the perforation rate was high for F2 versus F0/F1 tumors. Ulceration, tumor size ≥30 mm, and depressed histological type were independent risk factors for severe (F2) fibrosis. No fibrosis (F0) was observed in 77% (732/951) of endoscopically negative ulceration cases, whereas fibrosis was observed in 100% (76/76) of endoscopically positive cases. Masson trichrome staining was weak in 97% (710/732) of F0, moderate in 85% (181/214) of F1, and strong in 100% (81/81) of F2 cases., Conclusions: Histopathological type of submucosal fibrosis predicts outcome of ESD for EGC. Endoscopic indications of F2 submucosal fibrosis are ulceration, tumor ≥30 mm, and macroscopic depression.

Background and Aim: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is clinically useful in diagnosing gastric cancer and determining treatment options; however, there is a learning curve. Accurate FICE-based diagnosis requires training and experience. In addition, objectivity is necessary. Thus, a software program that can identify gastric cancer quantitatively was developed., Methods: A bag-of-features framework with densely sampled scale-invariant feature transform descriptors to magnifying endoscopy images of 46 mucosal gastric cancers was applied. Computer-based findings were compared with histologic findings. The probability of gastric cancer was calculated by means of logistic regression, and sensitivity and specificity of the system were determined., Results: The average probability was 0.78 ± 0.25 for the images of cancer and 0.31 ± 0.25 for the images of noncancer tissue, with a significant difference between the two groups. An optimal cut-off point of 0.59 was determined on the basis of the receiver operating characteristic curves. The computer-aided diagnosis system yielded a detection accuracy of 85.9% (79/92), sensitivity for a diagnosis of cancer of 84.8% (39/46), and specificity of 87.0% (40/46)., Conclusion: Further development of this system will allow for quantitative evaluation of mucosal gastric cancers on magnifying gastrointestinal endoscopy images obtained with FICE., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

It is relatively difficult to detect minute depressed (0-IIc) and flat (0-IIb) type early gastric cancers (EGCs) with ordinary endoscopic observation. Good preparation and washing out the mucus in the stomach are necessary for detection and correct diagnosis with chromoendoscopy using indigocarmine. It is important to diagnose whether EGC infiltration is submucosal (SM) deep or not, because the indication of endoscopic resection depends on the depths of the EGC. The characteristic endoscopic features of SM deep invasion in EGCs are related to macroscopic type, tumor size, histological type, fold convergency and endoscopic rigidity of the lesion area.

Background: The 2010 Japanese Gastric Cancer Association guidelines for the treatment of submucosal invasive gastric cancer (SM-GC) specify size 30 mm or less, differentiated-dominant histology, lack of vessel involvement, and submucosal invasion of less than 500 μm (SM1) as expanded criteria for curative endoscopic resection. Our purpose in this study was to confirm the validity of the expanded indications for curative endoscopic submucosal dissection (ESD) of SM-GC., Methods: The study subjects were 173 patients with SM-GC resected by ESD at Hiroshima University Hospital between April 2002 and September 2010, including 99 patients for whom 3-plus years' follow-up information was available. Post-ESD outcomes were compared between cases of SM1-GC that met the expanded ESD criteria, those that did not, and SM2-GC cases., Results: Complete resection was achieved for 93.2% of the SM1-GCs that met the expanded criteria. There was neither metastasis to lymph nodes or other organs nor local recurrence among the SM1-GCs. Disease-specific survival did not differ significantly between patients that were simply followed up after ESD and those that were treated by additional surgical resection., Conclusions: Our outcome data support the clinical validity of ESD without additional surgical resection for SM1-GCs that meet the expanded criteria.

Background: Although endoscopic submucosal dissection (ESD) is standard therapy in Japan for gastric epithelial neoplasm, the complication rate is unsatisfactory, with postoperative bleeding as the major complication. The aim of the present study was to determine risk factors for post-ESD bleeding in patients with gastric epithelial neoplasm., Patients and Methods: The study included 764 patients in whom 924 gastric epithelial neoplasms were resected endoscopically between June 2005 and December 2009: the period during which preventative coagulation for all exposed vessels on the artificial ulcer with hemostatic forceps upon completion of ESD was performed routinely. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors., Results: The post-ESD bleeding rate was 3.0%. Dialysis (vs no dialysis, P = 0.034), operation time ≥75 min (vs <75 min, P = 0.012) and poor control of bleeding during ESD (vs good control, P = 0.014) were significantly related to post-ESD bleeding. Poor control of bleeding during ESD (vs good control; P = 0.04) and operation time ≥75 min (vs <75 min; P = 0.012) were significantly related to bleeding after second-look endoscopy., Conclusions: Patients at high risk for post-ESD bleeding in gastric epithelial neoplasm were those undergoing dialysis, those in whom operation time was ≥75 min, and those in whom bleeding during ESD was poorly controlled. The latter two are risk factors for bleeding even after second-look endoscopy., (© 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.)

Objective: The conditions upon which endoscopic resection (ER) can be considered curative for submucosal invasive gastric cancer remain controversial; thus, unnecessary surgery is sometimes performed after ER. Our purpose is to evaluate the significance of several clinicopathological factors for predicting the absence of lymph node (LN) metastasis of submucosal invasive gastric cancer and thus determining cases in which ER can be considered curative., Patients and Methods: The study group comprised 220 patients with submucosal invasive gastric cancer that was resected surgically or endoscopically. Patients treated by ER underwent additional surgical resection. The presence of LN metastasis was evaluated in all patients, retrospectively., Results: LN metastasis was detected in 37 (16.8%) of the 220 patients. Independent risk factors for LN metastasis were width of submucosal invasion>6000 μm, lymphatic involvement, undifferentiated type at the deepest invasive portion, depth of submucosal invasion>1000 μm, and tumor diameter>30 mm. The group of 36 patients with submucosal invasion to a depth of ≤1000 μm, tumor diameter ≤30 mm, differentiated type as the dominant histologic type, and absence of vessel involvement was entirely free of LN metastasis (95% confidence interval, 0-8.0%)., Conclusions: Taken together, the five independent risk factors may allow expansion of the criteria for determining whether ER for submucosal invasive gastric cancer has been curative.

Background: The Flexible spectral Imaging Color Enhancement (FICE) system estimates the spectrum reflectance from a white-light endoscopic image and reconstitutes a color image from the wavelength, including useful information about the GI tract. The aim of this study was to investigate the usefulness of FICE with a specific wavelength in the assessment of early gastric cancers (EGCs), and the relationship between the FICE visualization and blood vessels., Design: A retrospective study., Setting: Department of Endoscopy, Hiroshima University, Hiroshima, Japan., Patients and Main Outcome Measurements: The study subjects consisted of 100 patients with EGCs (78 differentiated, 22 undifferentiated) who underwent an endoscopic or surgical resection. We analyzed the wavelengths to generate the maximum difference of the spectral reflectance between the normal gastric mucosa and the EGCs. We observed the same visual field first with white-light endoscopy and then with the FICE system. Then, we scored the demarcation of color between the cancer and the normal mucosa of white-light endoscopic observation and FICE observation, each without magnification. We examined the relationship between the score of the FICE image and the section of the vascular space., Results: The wavelength that generated the maximum difference in the tissue was 530 nm. The score of the FICE observation improved in 46 cases (46%), was unchanged in 54 cases (54%), and decreased in no cases (0%). There was a correlation between the score of the FICE images and the section of the vascular spaces., Conclusions: The FICE observation demonstrated that setting the wavelength at 530 nm resulted in an improvement in the visualization of the EGCs. It is thought that the FICE system is noninvasive and may more easily detect EGC without dye during both routine and detailed examinations.