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BackgroundNo prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality.MethodsWe conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores.ResultsWe enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05).ConclusionsWe derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available (https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android).

BackgroundThe incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan.MethodA multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage.ResultsThe proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers.ConclusionsSix- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.

PurposeDespite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab’s efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years.MethodsFrom March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups.ResultsThe median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37–1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68–2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535).ConclusionsNivolumab’s effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.

Purpose Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years. Methods We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan–Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno’s C-statistics. Results During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7% and 99.2%, respectively. No significant differences in OS were found among curability categories. The Cox proportional hazards model revealed the geriatric nutritional risk index (GNRI) and the Charlson comorbidity index (CCI) to be predictors of 3-year survival. We established a final model (EGC-2 model) expressed by GNRI − (2.2×CCI) with a cutoff value of 96. The overall survival rate was significantly lower in the model value < 96 group than in the model value ≥ 96 group ( P  < 0.001). Conclusions The prediction model using GNRI and CCI will be useful to support decision-making for the treatment of EGC in elderly patients aged ≥ 85 years.

PurposeThis study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM).MethodsOutcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS).ResultsAfter PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27–0.56 vs. HR 0.50; 95% CI 0.30–0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50–1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30–0.98 vs. HR 0.49; 95% CI 0.29–0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34–2.06).ConclusionThe comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

A severe Angelman syndrome (AS) patient with a very large deletion (19.3 Mb) at 15q11.2‐q14 required laryngotracheal separation, which is not a common surgery in AS. Comparative genomic hybridization‐based microarrays can be useful to confirm deletion size and clinical severity.

Since the last decade, endoscopic submucosal dissection (ESD) has been used as the standard treatment for superficial gastrointestinal neoplasms. Trainees learning ESD frequently encounter difficulties such as vascularity, peristalsis, and fibrosis during the procedure. Because individual vascularity differs, it generally cannot be consistently avoided. Given that massive hemorrhages can prolong the procedure time and diminish treatment efficacy and that insufficient vessel handling may also increase postoperative bleeding, hemorrhage control during ESD becomes important to ensure procedure safety. This article discusses methods for controlling hemorrhage during gastric ESD. Endoscopists should have a basic understanding of the vascular architecture and the high‐density areas in blood vessels, which are susceptible to intraoperative hemorrhage. Efficient preventative coagulation should be performed in addition to mastering the techniques for hemorrhage control using hemostatic forceps. Techniques useful for preventing intraoperative hemorrhage at every step (e.g. submucosal injection, mucosal incision, and dissection) should be learned. Gaining procedural competence and learning hemorrhage control techniques not only during ESD but also in daily work would help provide safe and effective treatment. Hemorrhage control during the endoscopic submucosal dissection is an important issue to ensure a safe procedure. A basic understanding of the vascular architecture and acquiring techniques useful for preventing intraoperative hemorrhage in the process are needed.

Recently, high concentrations of caffeine present in energy drinks and over-the-counter (OTC) drugs have become a concern worldwide. Several deaths due to caffeine intoxication have been reported, necessitating caution. Typically, supportive care is used to treat caffeine intoxication. However, in severe cases of caffeine intoxication, hemodialysis may be used. For adults, a lethal blood caffeine concentration is at least 80 µg/mL, whereas lethal blood caffeine concentration is unknown for children. In the present case, a 15-year-old girl took a large dose of an OTC antipyretic analgesic to commit suicide, resulting in caffeine intoxication. In this case, even though blood caffeine concentration was higher than the adult lethal dose, the patient recovered through a simple treatment with intravenous infusion of extracellular fluid.Recently, high concentrations of caffeine present in energy drinks and over-the-counter (OTC) drugs have become a concern worldwide. Several deaths due to caffeine intoxication have been reported, necessitating caution. Typically, supportive care is used to treat caffeine intoxication. However, in severe cases of caffeine intoxication, hemodialysis may be used. For adults, a lethal blood caffeine concentration is at least 80 µg/mL, whereas lethal blood caffeine concentration is unknown for children. In the present case, a 15-year-old girl took a large dose of an OTC antipyretic analgesic to commit suicide, resulting in caffeine intoxication. In this case, even though blood caffeine concentration was higher than the adult lethal dose, the patient recovered through a simple treatment with intravenous infusion of extracellular fluid.

PurposeWe assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies.MethodsThe medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted.ResultsA total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34–0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33–1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42–2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups.ConclusionsUpfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Background: The use of antithrombotic agents for the prevention of cerebro-cardioembolic events has increased, and recent guidelines have recommended the continued administration of low-dose aspirin (LDA) during endoscopic procedures with a high risk of bleeding. However, the influence of LDA on intraoperative bleeding control status during Endoscopic submucosal dissection (ESD) remains unclear. Methods: We examined 293 consecutive patients who underwent ESD for gastric cancers between January 2014 and February 2018. Patients administered with LDA (n = 52) were compared with those without antithrombotic therapy (n = 241; control) by propensity-score matching (PSM) concerning outcomes of ESD. Results: PSM analysis yielded 50 matched pairs. Comparison showed similar values for frequency of intraoperative major bleeding: 1 (0–4) times (median [range]) in the LDA group and 0 (0–5) in the control group respectively (p = 0.710). Others (frequency of preventive coagulation, procedure time, decrease of hemoglobin levels, en bloc resection, complete resection) were the same with a few adverse events including perforation (0%), and thromboembolism (0%). Postoperative bleeding rate was 1.9% in LDA group. Multivariate analysis indicated that location U and circumference on the posterior wall were associated with for multiple major intraoperative bleeding. Conclusion: The study suggests that gastric ESD can be safely accomplished without cessation of LDA.