Hideyuki Konishi

Background/Objectives: This study aimed to identify specific endoscopic findings associated with the development of GC following successful H. pylori eradication. Methods: This prospective multicenter observational study included patients who underwent annual surveillance endoscopy after successful H. pylori eradication therapy between September 2013 and June 2019. Endoscopic findings were evaluated one year after eradication therapy and analyzed using the Kyoto Classification of Gastritis to identify factors associated with GC development. Results: A total of 465 patients were included, including 49 patients with GC and 416 patients without GC. At the initial endoscopic assessment (median, 0.96 years post-eradication), emergence of map-like redness and invisible regular arrangement of collecting venule (RAC) as independent predictors of GC (map-like redness: hazard ratio [HR], 2.561; 95% confidence interval [CI], 1.362–4.572; p = 0.003; invisible RAC: HR, 3.131; 95% CI, 1.078–9.091; p = 0.036). Patients with map-like redness or invisible RAC showed a significantly higher incidence of GC than those without map-like redness or invisible RAC (p < 0.001 and p < 0.001, respectively). Notably, map-like redness and visible RAC appeared in 13% and 28.4% of cases within the first year after eradication, respectively. Conclusions: Map-like redness and invisible RAC were identified as independent predictors of GC following H. pylori eradication and may serve as early predictive indicators, appearing within one year of successful eradication. This finding underscores the importance of early surveillance endoscopy in identifying patients at elevated risk for GC.

The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 patients with qUC and 59 healthy controls (HCs) were enrolled (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and the Kyoto Encyclopedia of Genes and Genomes database. There were significant differences in fecal microbiota diversity between HC and qUC subjects, with 13 taxa characterizing each subject. Despite no significant difference in variation of microbiota in a single sample (α diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (β diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan–Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways.

Background: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. Methods: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. Results: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12–0.76). Conclusions: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.

The visibility and diagnostic accuracy of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication have been reported to improve using image-enhanced endoscopy (IEE) compared with white light imaging (WLI). The present study clarified the appropriate IEE for the detection and diagnosis of EGC in clinical settings. This prospective and cross-sectional study evaluated the visibility of EGC and endoscopic findings of gastric mucosa after successful HP eradication (n = 31) using videos with WLI and IEE. Three endoscopists evaluated high-definition videos in a randomized order. The mean visibility scores (MVSs) on linked color imaging (LCI) for atrophic border, intestinal metaplasia, map-like redness, and EGC were the highest among each modality (3.87 ± 0.34, 3.82 ± 0.49, 3.87 ± 0.50, and 3.35 ± 0.92, respectively). The MVSs with blue laser imaging (BLI) were highest for magnifying view of the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) for EGC (3.77 ± 0.49, 3.94 ± 0.25, and 3.92 ± 0.34, respectively). LCI had the highest visibility among findings of gastric mucosa and EGC after HP eradication, and BLI had the highest visibility of MVP, MSP, and DL in magnifying observation. These results suggest that LCI observation in the entire stomach and further magnifying BLI are the best methods for detecting and diagnosing EGCs after HP eradication, respectively.

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.

The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity. We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline. The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67). Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure.

Background/Aims. The aim of this study was to evaluate the endoscopic recognition of esophageal squamous cell carcinoma (ESCC) using four different methods (Olympus white light imaging (O-WLI), Fujifilm white light imaging (F-WLI), narrow band imaging (NBI), and blue laser imaging- (BLI-) bright).Methods.We retrospectively analyzed 25 superficial ESCCs that had been examined using the four different methods. Subjective evaluation was provided by three endoscopists as a ranking score (RS) of each image based on the ease of detection of the cancerous area. For the objective evaluation we calculated the color difference scores (CDS) between the cancerous and noncancerous areas with each of the four methods.Results. There was no difference between the mean RS of O-WLI and F-WLI. The mean RS of NBI was significantly higher than that of O-WLI and that of BLI-bright was significantly higher than that of F-WLI. Moreover, the mean RS of BLI-bright was significantly higher than that of NBI. Furthermore, in the objective evaluation, the mean CDS of BLI-bright was significantly higher than that of O-WLI, F-WLI, and NBI.Conclusion. The recognition of superficial ESCC using BLI-bright was more efficacious than the other methods tested both subjectively and objectively.

Purpose. The aim of this study was to examine the characteristics of difficult cases and the learning curve in colorectal endoscopic submucosal dissection (ESD).Methods. We studied 518 colorectal tumors treated by ESD. Patients were divided into 2 groups such as the difficult ESD group and non-difficult ESD group in view of procedure time and procedure speed, respectively. The clinical features in each group were analyzed, and we also examined cases with severe fibrosis. Furthermore, we divided all cases into 5 periods according to experience of ESDs and investigated the rates of difficult and perforation cases.Results. In view of both procedure time and procedure speed, there were significant differences about mean tumor size, rates of severe fibrosis and perforation, and en bloc resection rate between the two groups. Severe fibrosis was detected in protruding tumors >40 mm in diameter. With respect to the learning curve, the rate of difficult and perforation cases decreased significantly in the late periods compared to the first period.Conclusions. Large tumor size, high rates of severe fibrosis and perforation, and low rate of en bloc resection are related with difficult ESD cases. The increasing of experiences can decrease the rate of difficult cases and perforation.