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For pancreatic masses, an evaluation of their vascularity using contrast-enhanced ultrasonography can help improve their characterization. This study was designed to evaluate the utility and safety of contrast-enhanced transabdominal ultrasonography (CE-TUS) and endoscopic ultrasonography (CE-EUS) in the diagnosis of pancreatic masses including solid or cystic masses. This multi-center comparative open-label superiority study is designed to compare Plain (P)-TUS/EUS alone with P-TUS/P-EUS plus CE-TUS/CE-EUS. Three hundred and one patients with a total of 232 solid pancreatic masses and 69 cystic masses were prospectively enrolled. The primary endpoints are to compare the diagnostic accuracy between P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for both the TUS and EUS of solid pancreatic masses, and to compare the diagnostic accuracy between P-EUS alone and P-EUS plus CE-EUS in cystic pancreatic masses. The secondary endpoints are to compare the diagnostic sensitivity and specificity of P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for pancreatic solid/cystic masses, and the accuracy of P-TUS alone and P-TUS plus CE-TUS for pancreatic cystic masses. Other secondary endpoints included comparing the diagnostic sensitivity, specificity, and accuracy of CE-TUS, CE-EUS and CE-computed tomography (CT) for solid/cystic pancreatic masses. The safety, degree of effective enhancement, and diagnostic confidence obtained with CE-TUS/CE-EUS will also be assessed. [ABSTRACT FROM AUTHOR]

Background and aims: Malignant gastric outlet obstruction (GOO) can be palliated by endoscopic placement of self-expandable metal stents (SEMSs). Studies comparing uncovered (USEMSs) and covered (CSEMSs) SEMSs have yielded inconclusive results. This meta-analysis compared USEMSs with CSEMSs in patients with GOO caused by intrinsic and extrinsic tumors. Methods: Potentially relevant articles were identified by searching PubMed, the Cochrane Library, and Medline. The primary outcome was stent dysfunction. Relationships between characteristics of tumors causing GOO and the stent dysfunction rate following USEMSs and CSEMS placement were assessed. Results: Overall, six randomized controlled trials and 12 observational studies, including 2431 patients, were identified. Rate of stent dysfunction did not differ significantly between USEMSs and CSEMSs (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.73–1.25, I2 = 44%), but there was heterogeneity. Meta-regression analysis showed that heterogeneity of stent dysfunction was caused by a difference in the ratio of intrinsic-to-extrinsic tumors causing GOO between studies (coefficient, 0.944; 95% CI, 0.30–1.58). Studies were divided into intrinsic and extrinsic tumor groups. Subgroup analysis showed that the stent dysfunction rate did not differ between USEMSs and CSEMSs in the intrinsic tumor group (OR, 1.10; 95% CI, 0.85–1.41; I2 = 32%). In the extrinsic tumor group, USEMS was associated with a lower rate of stent dysfunction than CSEMS (OR, 0.64; 95% CI, 0.47–0.87; I2 = 25%). Conclusion: USEMS and CSEMS placement generally showed comparable outcomes among patients with GOO. USEMS was more effective than CSEMS for patients with GOO caused by extrinsic tumors. [ABSTRACT FROM AUTHOR]

The incidence and mortality rates of pancreatic cancer (PC) are increasing. It is important to discriminate PC from the other pancreatic lesions; however, differential diagnosis based on conventional transabdominal ultrasound (US) remains challenging even though US is often the first examination performed. Transabdominal contrast-enhanced ultrasound (CEUS) has high diagnostic accuracy for PC. This meta-analysis aimed to examine the utility of low-mechanical-index CEUS with enhancement for PC diagnosis. A systematic meta-analysis of all potentially relevant articles was performed. Fixed-effects or random-effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio (LR) and negative LR. The study enrolled 983 patients from nine eligible studies. The pooled estimates of sensitivity and specificity were 92% (95% confidence interval [CI]: 0.89-0.94) and 76% (95% CI: 0.71-0.81), respectively. The diagnostic odds ratio (DOR) for CEUS was high (53.62). The area under the summary receiver operating characteristic curve was 0.95. Funnel plots revealed no publication bias, and there was no significant relationship between the DORs and study characteristics, including continent, type of contrast agent, contrast agent dosage and scan phase. Only number of patients affected diagnostic ability. This meta-analysis indicates that CEUS with enhancement pattern is useful for diagnosis of PC. [ABSTRACT FROM AUTHOR]

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications. Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis. Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31–0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03–10.84). Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT. [ABSTRACT FROM AUTHOR]

Background: Current imaging modalities are limited in their ability to distinguish pancreatic cancer (PC) from non‐neoplastic pancreatic lesions. The diagnostic use of contrast‐enhanced endoscopic ultrasonography (CE‐EUS) has increased, and its utility has been reported. Recently, contrast‐enhanced harmonic EUS (CH‐EUS) was reported to facilitate imaging of parenchymal perfusion and microvessels in pancreatobiliary diseases, leading to a high diagnostic accuracy for PC. The present meta‐analysis aims to investigate the usefulness of CH‐EUS with enhancement pattern for PC diagnosis. Methods: A systematic meta‐analysis of all potentially relevant articles identified in PubMed, the Cochrane library, and Medline was carried out. Fixed‐effects or random‐effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI). Results: The study enrolled 887 patients from nine eligible studies. Pooled estimates of sensitivity and specificity were 93% (95% CI, 0.91–0.95) and 80% (95% CI, 0.75–0.85), respectively. Subgroup analyses were carried out on the main results after excluding two outliers. Area under summary receiver operating characteristics curve was 0.97. No publication bias was found using funnel plots. No significant relationship was found between the diagnostic odds ratios and the characteristics of the studies including continent and contrast agent. Conclusions: This meta‐analysis showed that CH‐EUS with qualitative analysis of enhancement pattern is useful for the diagnosis of PC, and has high sensitivity and accuracy, regardless of the type of contrast agent used. This modality may provide improved diagnostic accuracy for PC in clinical practice. [ABSTRACT FROM AUTHOR]

Background: S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. Methods: IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80–120 mg for 21 days plus cisplatin 60 mg/m2 (q5w)) or XP (capecitabine 2000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w)). Results: In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7 months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1 months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0 months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2 months) than in the XP group (11.1 months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2 months) and in the XP group (12.4 months) (HR, 0.868; P = 0.476). Conclusions: SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. Clinical Trial Registration: The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively. [ABSTRACT FROM AUTHOR]

We conducted a prospective multicenter phase II trial of patients with borderline resectable pancreatic carcinoma to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine thera py on ov erall survival (OS). The clinical trial primarily evaluated OS time from the first day of protocol therapy as a primary endpoint. The secondary endpoints were recurrence-free survival from the first day of protocol therapy, safety of the protocol therapy (adverse effect), mor-bidity based on the Clavien Dindo classification of more than III, response rate, preoperative/postoperative tumor marker (CA 19-9, CEA), rate of normalization, reduction rate of the maximum standardized uptake value on positron emission tomography-computed tomography (limited to institutions where positron emission tomography-computed tomography was available), chemotherapeutic effect grade based on Evans' classification, resection rate, R0 resection rate, surgical data (operative time, blood loss, transfusion, postoperative hospital day), overall morbidity rates (reoperation, rate of readmission, mortality), patient rate in postoperative adjuvant therapy (entry rate, completion rate), dose intensity, quality of life regarding fatigue and malaise assessed by the questionnaire of FACIT-F (Japanese version), and peripheral sensory neuropathy assessed by the questionnaire of the FACT/GOG-NTX subscale (version 4; Japanese version). Sixty patients were included in the study, and 18 leading Japanese institutions and hospitals (all high-volume centers in pancreatic surgery) participated in this trial. [ABSTRACT FROM AUTHOR]

The increasing scientific attention given to precision medicine based on real‐world data has led to many recent studies clarifying the relationships between treatment effects and patient characteristics. However, this is challenging because of ubiquitous heterogeneity in the treatment effect for individuals and the real‐world data on their backgrounds being complex and noisy. Because of their flexibility, various machine learning (ML) methods have been proposed for estimating heterogeneous treatment effect (HTE). However, most ML methods incorporate black‐box models that hamper direct interpretation of the relationships between an individual's characteristics and treatment effects. This study proposes an ML method for estimating HTE based on the rule ensemble method RuleFit. The main advantages of RuleFit are interpretability and accuracy. However, HTEs are always defined in the potential outcome framework, and RuleFit cannot be applied directly. Thus, we modified RuleFit and proposed a method to estimate HTEs that directly interpret the relationships among the individuals' features from the model. Actual data from an HIV study, the ACTG 175 dataset, was used to illustrate the interpretation based on the ensemble of rules created by the proposed method. The numerical results confirm that the proposed method has high prediction accuracy compared to previous methods, indicating that the proposed method establishes an interpretable model with sufficient prediction accuracy. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011–2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions. [ABSTRACT FROM AUTHOR]

Postural abnormalities in Parkinson's disease (PD) can devastatingly impair the quality of life, especially in patients with advanced disease, and are generally refractory to dopaminergic agents. The objective of this exploratory study was to investigate the efficacy and safety of istradefylline for the treatment of postural abnormalities in PD. In this open-label, 24-week, single-arm prospective trial, PD patients with postural abnormalities experiencing the wearing-off phenomenon on levodopa-containing therapies were enrolled and received a starting dose of 20 mg/day istradefylline orally for 4 weeks, which was then increased to 40 mg/day. The primary endpoint was the change from baseline to week 24 in the 14-item Unified Dystonia Rating Scale (UDRS) total score. Pivotal secondary endpoints were changes in the sub-items of UDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, and adverse drug reactions (ADRs). Overall, 24/31 enrolled patients completed the study; mean (standard deviation) age and duration of motor complications were 73.3 (7.7) years and 3.2 (4.4) years, respectively. Mean (95% confidence interval [CI]) change in the UDRS total score was 4.84 (1.97, 7.71; P = 0.002), with significant improvements in the neck, right distal arm and hand, and trunk severity scores. Mean (95% CI) change in the MDS-UPDRS part III score was 7.84 (4.34, 11.34; P < 0.001). The most common ADRs were malaise, dyskinesia exacerbation, and visual hallucinations in 2 (6.5%) patients each. This exploratory study demonstrated that istradefylline could be efficacious for postural abnormalities and was generally well tolerated in patients with PD experiencing the wearing-off phenomenon with levodopa-containing therapies. [Display omitted] • Patients with advanced Parkinson's disease (PD) have postural abnormalities (PAs). • The 14-item Unified Dystonia Rating Scale (UDRS) was used for rating PAs. • PD patients on levodopa experiencing wearing-off received add-on istradefylline. • Istradefylline treatment improved the UDRS total score. • Efficacy of istradefylline in PAs was independent of the use of dopamine agonists. [ABSTRACT FROM AUTHOR]

Abstract: There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5-Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow-up of 17days. The primary outcome was short-term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short-term change in the short form of the McGill pain questionnaire (SF-MPQ), cumulative changes in the following scores (VAS, SF-MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty-four NP patients were included in the intention-to-treat analysis. The real rTMS, compared with the sham, showed significant short-term improvements in VAS and SF-MPQ scores without a carry-over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients. [Copyright &y& Elsevier]

Costovertebral angle (CVA) tenderness is an important finding in the diagnosis of acute focal bacterial nephritis. There are no data about the association between the depth of the kidney and CVA tenderness positivity. The authors define skin-to-renal pelvis distance as a parameter of kidney depth and propose that skin-to-renal pelvis distance can be a predictive parameter of CVA tenderness in patients with acute focal bacterial nephritis. Objectives: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN). Methods: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition. Results: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45–81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70–1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness (P = 0.038, odds ratio 0.76, 95% confidence interval 0.590–0.986). Conclusions: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited. [ABSTRACT FROM AUTHOR]

Simple Summary: There is no clear preference between S-1 and capecitabine in combination with platinum agent as first-line therapy for patients with HER2-negative unresectable advanced or recurrent gastric cancer (GC) with measurable disease. Although a distinguishing use of S-1 versus capecitabine based on histological classification has been studied, the present integrated analysis, using 162 individual participant data of GC patients with measurable disease, is the first to show that S-1 plus cisplatin (SP) achieves deeper tumor shrinkage than capecitabine plus cisplatin (XP), leading a longer overall survival although no differences in response rate or progression-free survival in differentiated GC. On the other hand, in undifferentiated GC, SP consistently showed better clinical results than XP. These findings thus have implications for the choice of oral fluoropyrimidine in the era of first line therapy in combination with oxaliplatin and immune checkpoint inhibitor. It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology. [ABSTRACT FROM AUTHOR]

Abstract: We studied the effects of extending the rotation period (long-rotation) and related ecological variables on the biodiversity of six beetle families in larch (Larix kaempferi) plantations. Beetle diversity in the forest understory and the canopy of long-rotation and middle-aged plantations was compared. The relationships between the species richness of each beetle family and 24 ecological variables were identified. We found that beetle diversity tended to increase with long-rotation and responded differently to the ecological variables in two woodland strata (understory and canopy); e.g., an increase in phytophagies occurred in the canopy. Among the 24 measured ecological variables, the species richness of naturally regenerated mature trees, their abundance, and the quality and quantity of coarse woody material (CWM) had the strongest influences on beetle diversity. The former two variables increased with long-rotation; however, most variables related to CWM did not increase because thinned trees were left in middle-aged plantations as fallen logs. Therefore, the occurrence of naturally regenerated native trees that had grown sufficiently tall to reach canopy height in long-rotation plantations underpinned the improved biodiversity in larch plantations, contributing to native beetle species richness in these woodlands. Long-rotation makes plantations more heterogeneous, particularly in the canopy, and promotes greater native beetle diversity. [Copyright &y& Elsevier]

Intraductal papillary mucinous neoplasms (IPMNs) have a wide pathologic spectrum and it can be difficult to diagnose malignancy, including pathological grade. The aim of this study was to evaluate contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for the diagnosis of malignant IPMN and IPMN-associated invasive carcinoma (invasive IPMC). From 5009 patients diagnosed with IPMN at Wakayama medical university between December 2009 and December 2021, 115 patients who underwent contrast-enhanced computed tomography (CE-CT), conventional EUS, CH-EUS, and surgical resection were enrolled. The detection of mural lesions was compared with pathological findings. Malignant IPMN and invasive IPMC were also assessed according to mural lesion size and vascularity on CH-EUS. CH-EUS and conventional EUS showed significantly higher accuracy than CE-CT in the detection of mural nodules (92%, 83%, and 72%, respectively) and diagnosis of malignant IPMN (75%, 73%, and 63%, respectively). An early wash-out pattern on CH-EUS was observed in significantly more patients with invasive IPMC than in those with low-, intermediate-, or high-grade dysplasia. When compared with CE-CT, CH-EUS was significantly more accurate for detecting mural nodules and more useful for diagnosing malignant IPMN. The vascular pattern on CH-EUS was also useful for diagnosing invasive IPMC. [ABSTRACT FROM AUTHOR]

We propose a novel framework based on the RuleFit method to estimate heterogeneous treatment effect in randomized clinical trials. The proposed method estimates a rule ensemble comprising a set of prognostic rules, a set of prescriptive rules, as well as the linear effects of the original predictor variables. The prescriptive rules provide an interpretable description of the heterogeneous treatment effect. By including a prognostic term in the proposed model, the selected rule is represented as an heterogeneous treatment effect that excludes other effects. We confirmed that the performance of the proposed method was equivalent to that of other ensemble learning methods through numerical simulations and demonstrated the interpretation of the proposed method using a real data application. [ABSTRACT FROM AUTHOR]

Objectives: The role of a covered vs. an uncovered self‐expandable metal stent (SEMS) for malignant distal biliary obstruction (MDBO) is not clear. This meta‐analysis compared the efficacy of covered vs. uncovered SEMS for patients with MDBO after endoscopic insertion. Methods: A systematic meta‐analysis of all relevant articles listed in PubMed, the Cochrane Library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled effects with 95% confidence intervals (CIs). Results: The meta‐analysis included 2358 patients from 12 eligible studies. Time to recurrent biliary obstruction (RBO) was significantly longer for covered SEMS (mean difference, 45.51 days; 95% CI 11.79–79.24). Although there was no significant difference in the RBO rate, subgroup analysis in pancreatic cancer occupying more than 90% (PC) revealed that the RBO rates were significantly lower for covered SEMS (odds ratio [OR] 0.43, 95% CI 0.25–0.74). Stent migration, sludge formation, and overgrowth were significantly more common with a covered SEMS (OR 7.92, 95% CI 4.01–15.64; OR 3.25, 95% CI 1.89–5.59; OR 2.03, 95% CI 1.20–3.43, respectively). The rate of ingrowth was significantly lower for covered SEMS. There was no significant difference in total procedure‐related adverse events between the two types of SEMS. Conclusions: A covered SEMS is superior to an uncovered SEMS with respect to prevention of RBO in patients with MDBO, particularly those caused by PC. [ABSTRACT FROM AUTHOR]

Background: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). Methods: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. Results: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13–83.0, P = 0.028). Conclusion: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates. [ABSTRACT FROM AUTHOR]

Background: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6–8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. Methods: Data from consecutive, untreated patients with histopathologically confirmed stage I–III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. Results: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient − 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. Conclusion: ED administration for 6–8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. Clinical Trial Registration: UMIN000023455. [ABSTRACT FROM AUTHOR]

Background and aims: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). Methods: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. Results: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76–12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. Conclusion: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS. [ABSTRACT FROM AUTHOR]

Background: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)‐based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. Methods: This is a prospective, single‐centered, open‐label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP‐based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. Results: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). Conclusions: Mannitol should remain the standard diuresis in CDDP‐based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance. [ABSTRACT FROM AUTHOR]

Background: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. Methods: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1–14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. Results: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%–64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes eventual death through respiratory failure unless mechanical ventilation is provided. Brain–machine interfaces (BMIs) may provide brain control supports for communication and motor function. We investigated the interests and expectations of patients with ALS concerning BMIs based on a large-scale anonymous questionnaire survey supported by the Japan Amyotrophic Lateral Sclerosis Association. Methods: We surveyed 1918 patients with ALS regarding their present status, tracheostomy use, interest in BMIs, and their level of expectation for communication (conversation, emergency alarm, internet, and writing letters) and movement support (postural change, controlling the bed, controlling household appliances, robotic arms, and wheel chairs). Findings: Seven hundred and eighty participants responded. Fifty-eight percent of the participants underwent tracheostomy. Approximately, 80% of the patients experienced stress or trouble during communication. For all nine supports, > 60% participants expressed expectations regarding BMIs. More than 98% of participants who underwent tracheostomy expected support with conversation and emergency alarms. Participants who did not undergo tracheostomy exhibited significantly greater expectations than participants with tracheostomy did regarding all five movement supports. Seventy-seven percent of participants were interested in BMIs. Participants aged < 60 years had greater interest in both BMIs. Interpretation: This is the first large-scale survey to reveal the present status of patients with ALS and probe their interests and expectations regarding BMIs. Communication and emergency alarms should be supported by BMIs initially. BMIs should provide wide-ranging and high-performance support that can easily be used by severely disabled elderly patients with ALS. [ABSTRACT FROM AUTHOR]

Objective: Predicting prognosis is a complex process, particularly in patients with severe sepsis or septic shock. This study aimed to determine the relationship between the Sequential Organ Failure Assessment (SOFA) scores for individual organs during the first week of admission and the in-hospital mortality in patients with sepsis. Methods: This study was a post hoc evaluation of the Japan Septic Disseminated Intravascular Coagulation study and included patients admitted to 42 intensive care units in Japan for severe sepsis or septic shock, between January 2011 and December 2013. We assessed the relationship between the organ and total SOFA scores on days 1, 3, and 7 following admission and the in-hospital mortality using logistic regression analysis. Results: We evaluated 2732 patients and found the in-hospital mortality rate was 29.1%. The mean age of the patients (standard deviation) was 70.5 (14.1) years, and the major primary site of infection was the abdomen (33.6%). The central nervous system (CNS) SOFA score exhibited the strongest relationship with mortality on days 1 (adjusted odds ratio [aOR]: 1.49, 95% confidence interval [CI]: 1.40-1.59), 3 (aOR: 1.75, 95% CI: 1.62-1.89), and 7 (aOR: 1.93, 95% CI: 1.77-2.10). The coagulation SOFA scores showed a weak correlation with mortality on day 1, but a strong correlation with mortality on day 7 (aOR: 2.04, 95% CI: 1.87-2.24). Conclusions: The CNS SOFA scores were associated with mortality in patients with severe sepsis on days 1, 3, and 7 following hospitalization. The coagulation SOFA score was associated with mortality on day 7. In clinical situations, the CNS SOFA scores during the acute phase and the CNS SOFA and coagulation SOFA scores during the subsequent phases should be evaluated in order to determine patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was developed with the aim of further improving the diagnostic performance of endoscopic ultrasound. Although novel puncture needles have been specifically designed for collecting sufficient tissue specimens, clinical studies have indicated no clear difference in diagnostic performance between these novel needles and conventional puncture needles. Recently, a needle with Franseen geometry was developed specifically for EUS-FNA biopsy. Due to the characteristic shape of its tip, the Franseen needle is expected to be effective for scraping tissues, thus potentially increasing the diagnostic accuracy of EUS-FNA biopsy. We plan to carry out a prospective, multicenter, open-labeled, controlled trial to compare conventional and Franseen needles in terms of the diagnostic accuracy of EUS-FNA for evaluating the malignancy of pancreatic mass lesions.Methods/design: The study will enroll 520 patients with pancreatic mass managed at any of 21 participating endoscopic centers. Lesion samples obtained using 22G conventional and Franseen needles will be assessed to compare the efficacy and safety of these two types of needles in EUS-FNA for evaluating the malignancy of mass lesions in the pancreas. Tissue samples will be fixed in formalin and processed for histologic evaluation. For the purpose of this study, only samples obtained with the first needle pass will be used for comparing the: (i) accuracy of the malignancy diagnosis, (ii) sensitivity and specificity for the malignancy diagnosis, (iii) procedure completion rate, (iv) sample cellularity, and (v) incidence of complications. Patient enrollment begins on July 17, 2018.Discussion: The outcomes of this study may provide insight into the optimal needle choice for evaluating the malignancy of pancreatic solid lesions, thus aiding in the development of practice guidelines for pancreatic diseases.Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000030634. Registered on 29 December 2017. http://www.umin.ac.jp/ Version number: 01.2017.12.28. [ABSTRACT FROM AUTHOR]

Background: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). Patients and methods: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. Results: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5–90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. Conclusion: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. Trial registration: Registration number: UMIN00000714 and UMIN000004440. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. Methods: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT (+) GISTs. Imatinib (400 mg/d) was given for 6–9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. Results: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. Conclusions: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence. [ABSTRACT FROM AUTHOR]

Background: The development of triplet regimens for advanced gastric cancer is challenging. The aim of this phase I dose-escalation study was to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naïve patients with HER2-negative advanced gastric cancer. Methods: The 3 + 3 design was adopted. Every 4 weeks, patients received an escalating dose of intravenous irinotecan (100–150 mg/m2) on day 1 and fixed doses of intravenous cisplatin (60 mg/m2) on day 1 and oral S-1 (80 mg/m2) on days 1 to 14. Results: Twelve patients were enrolled in two dose level cohorts. In the level 1 cohort (irinotecan 100 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicity including grade 4 neutropenia and febrile neutropenia occurred in one of six patients, whereas in the level 2 cohort (irinotecan 125 mg/m2, cisplatin 60 mg/m2, and S-1 80 mg/m2), dose-limiting toxicities including grade 4 neutropenia developed in two of six patients. Thus, the level 1 and 2 doses were determined to be the recommended and maximum tolerated doses, respectively. Common grade 3 or higher adverse events were neutropenia (75%; n = 9), anemia (25%; n = 3), anorexia (8%; n = 1), and febrile neutropenia (17%; n = 2). Irinotecan, cisplatin, and S-1 combination therapy achieved an overall response rate of 67% with a median progression-free survival and overall survival of 19.3 and 22.4 months, respectively. Conclusions: The potential treatment efficacy of this triplet regimen in HER2-negative advanced gastric cancer warrants further evaluation, especially in patients requiring intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Detective flow imaging endoscopic ultrasonography (DFI-EUS) is an innovative imaging modality that was developed to detect fine vessels and low-velocity blood flow without contrast agents. We evaluate its utility for the differential diagnosis of gallbladder lesions and intraductal papillary mucinous neoplasms (IPMNs). We enrolled patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS for gallbladder lesions or IPMNs. The detection of vessels using DFI-EUS and e-FLOW EUS was compared with that via contrast-enhanced EUS and pathological findings. The vessel pattern was also categorized as regular or irregular. Of the 33 lesions included, there were final diagnoses of 13 IPMNs and 20 gallbladder lesions. DFI-EUS was significantly superior to e-FLOW EUS for discriminating between mural nodules and mucous clots and between solid gallbladder lesions and sludge using the presence or absence of vessel detection in lesions (p = 0.005). An irregular vessel pattern with DFI-EUS was a significant predictor of malignant gallbladder lesions (p = 0.002). DFI-EUS is more sensitive than e-FLOW-EUS for vessel detection and the differential diagnosis of gallbladder lesions and IPMNs. Vessel evaluation using DFI-EUS may be a useful and simple method for differentiating between mural nodules and mucous clots in IPMN, between solid gallbladder lesions and sludge, and between malignant and benign gallbladder lesions. [ABSTRACT FROM AUTHOR]

Background: The histological features and radiological shape of extrahepatic cholangiocarcinoma (eCCA) have not been widely studied in relation to prognosis. Multi-detector computed tomography (MDCT) is thought to be useful in diagnosis of progress and tumor distribution; it can also show morphological differences (round, triangular, and square forms) at the tumoral obstruction sites. Histological types of eCCA may be revealed, with potential association with tumor growth and survival. Methods: We examined the distribution of tumor radiological shape subtypes on MDCT. The surgical outcomes of consecutive patients with eCCA who underwent macroscopic curative resection were reviewed. Results: CT subtypes in 109 patients were 62 triangular, 35 square, and 12 round. There were clear prognostic differences in long-term survival rates (P < 0.001); 5-year survival rates were 100% in round, 64% in triangular, and 19% in square types. There was no recurrence in any cases of round-type tumor at the site of obstruction. Depth of tumor invasion and rates of nodal involvement were significantly higher in triangular and square-type tumors than in round-type tumors. In papillary adenocarcinoma, radiological obstructions were round type in seven patients (78%) and triangular type in two patients (22%). In tubular adenocarcinoma, all round-type tumors were well differentiated, the ratio of square-type tumors increasing as the degree of differentiation decreased from "well" to "moderate," and "poor" respectively (23%, 39%, 57%; P = 0.033). Conclusions: Tumor radiological shape predicts tumor progression, histological type, and survival in eCCA. This information may be helpful in preoperative radiological staging on MDCT. [ABSTRACT FROM AUTHOR]

Background: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC. Methods: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching. Results: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group. Conclusion: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. Methods: Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. Results: Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2–13.0 kg was proposed for underweight, 7.3–12.5 kg for normal weight, and 2.0–9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. Conclusions: To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages. [ABSTRACT FROM AUTHOR]

Background: Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib. Methods: This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day. Results: Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%. Conclusion: Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients. Trial registration: Japan Registry of Clinical Trials ID: jRCTs051180008, registered date: 08/11/2018. [ABSTRACT FROM AUTHOR]

Background: Spastic hemiplegia causes slow and unstable walking in post-stroke patients. Dynamic tilt table with robotic leg movement (DTTRLM) is safe and effective in improving walking. Functional electric stimulation (FES) improves walking speed in post-stroke patients with spastic hemiplegia. The aim of this study was to determine the effects of combined DTTRLM + FES on walking speed compared with DTTRLM alone. Methods: Twenty post-stroke patients were randomly assigned to receive either a single session of stepping + FES treatment or a single session of stepping alone treatment. After a one-week washout period, the same two groups underwent a single session of the other treatment, and the same measurements were taken. We measured walking speed, cadence, and the number of steps in a 10 m walking test (10MWT) and assessed Modified Ashworth Scale (MAS), Fugl–Meyer Assessment (FMA), and range of motion (ROM) before and after the intervention. Results: Stepping + FES significantly improved walking speed, number of steps, and ankle inversion ROM, compared with stepping alone. Adverse events were not observed in any subject. Conclusions: Robotic stepping therapy combined with FES significantly improved 10 m walking speed (10MWS) compared with stepping only in patients with post-stroke and spastic hemiplegia. Further studies are needed to determine the long-term effects of the combination treatment. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) is less accurate in obtaining samples from gastrointestinal subepithelial lesions (SELs) ≤2 cm than from pancreatic cancers. The present study compared the usefulness of 22G Fork-tip and Franseen needles for EUS-TA and assessed the ability of contrast-enhanced harmonic EUS (CH-EUS) to diagnose SELs ≤2 cm. Fifty-seven patients who underwent EUS-TA for SELs ≤2 cm were evaluated. The primary endpoint was to compare the rate of acquisition of sufficient samples by these two needles. Secondary endpoints included technical success rate, adverse events, numbers of needle passes, and diagnostic ability of CH-EUS for SELs. Of the 57 included patients, 23 and 34 underwent EUS-TA with Fork-tip and Franseen needles, respectively. Technical success rates were 100% with both needles and adverse events occurred in zero (0%) and one (2.9%) patient with Fork-tip and Franseen needles, respectively. The rate of adequate sample acquisition was significantly higher using Fork-tip than Franseen needles (96% vs. 74%; p = 0.038). The hyper- or iso-vascular pattern on CH-EUS correlated significantly with a diagnosis of gastrointestinal stromal tumor (p < 0.001). EUS-TA with Fork-tip needles were superior to EUS-TA with Franseen needles in acquiring sufficient samples and CH-EUS was also useful for the diagnosis of SELs ≤2 cm. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between activity of the small intestinal villi and the effectiveness of chemotherapy remains unclear. This study aimed to investigate how serum diamine oxidase (DAO) activity affects antitumor effects, adverse events, and amino acid absorption.Methods: We performed a single-center prospective cohort study that enrolled 50 patients with esophageal cancer (EC) receiving docetaxel, cisplatin, and 5-fluorouracil therapy. We determined the cut-off value of serum DAO activity contributing to a response to chemotherapy using a generalized additive model. Additionally, we compared adverse events, inflammatory markers, blood amino acid levels, and quality of life between the high and low DAO activity groups during chemotherapy.Results: The cut-off value of serum DAO activity at the first visit that contributed to a chemotherapy response was 6.5 units/L. Leukopenia and neutropenia of grade ≥ 3 were significantly higher in the DAO low (< 6.5 units/L) group (p = 0.044, 0.017, respectively). Interleukin-6 was significantly lower in the DAO high (≥ 6.5 units/L) group at the first visit and at 4 weeks after the end of chemotherapy (p = 0.039, 0.011, respectively). Glutamine was higher in the DAO high group at all measurement points during chemotherapy. Fatigue was significantly lower in the DAO high group (p = 0.001).Conclusion: Serum DAO activity may be a predictor of the response to chemotherapy in patients with EC. The absorption capacity of amino acids was maintained in the group with high DAO activity, which may have contributed to the anti-inflammatory effect and provided a background for reducing adverse events. [ABSTRACT FROM AUTHOR]

Background: Large type 3 and type 4 gastric cancers have extremely poor prognoses. To address this, neoadjuvant chemotherapy may be a promising approach. The phase III JCOG0501 study, conducted to confirm the superiority of neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy over upfront surgery, showed no survival benefit for neoadjuvant S-1 plus cisplatin. In Korea, the PRODIGY study, which was a phase III study of neoadjuvant docetaxel plus oxaliplatin plus S-1 (DOS) followed by surgery and adjuvant S-1 versus surgery and adjuvant S-1 for gastric cancer of T2-3N+ or T4Nany, showed that progression-free survival (PFS) was significantly superior in the neoadjuvant DOS arm. Therefore, DOS therapy may be a promising candidate for preoperative chemotherapy for large type 3 or type 4 gastric cancer.Methods: Preoperative docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 will be intravenously administered on day1 every three weeks. S-1 will be orally administered 80 mg/m2 on days 1-14 of a 21-day cycle. Patients will receive three courses of treatment and gastrectomy with ≥D2 lymph node dissection. Postoperative S-1 plus docetaxel therapy (DS) will be administered according to the JACCRO GC-07 (START-2) study. The primary endpoint is the 3-year PFS rate. Secondary endpoints include PFS time, overall survival time, pathological response rate, response rate according to RECIST version1.1, proportion of completion of neoadjuvant chemotherapy, R0 resection rate, proportion of completion of surgery, proportion of completion of protocol treatment, proportion of negative conversion of CY, adverse event occurrence rate, and nutritional evaluation. The null hypothesis for the 3-year PFS rate is 45% and the expected value is 60%. The total sample size is 46 considering that the registration period and follow-up period are two and three years, respectively.Discussion: This is a prospective, multicenter, single-arm, open-label, phase II trial assessing the efficacy and safety of preoperative DOS and postoperative DS for large type 3 or type 4 gastric cancer. The results will inform future phase III trials and are expected to lead to new treatment strategies for large type 3 or type 4 gastric cancer.Trial Registration: Registered with Japan Registry of Clinical Trials on October 11, 2019 ( jRCTs051190060 ). [ABSTRACT FROM AUTHOR]

Background: Although docetaxel plus S-1 adjuvant chemotherapy after gastrectomy with D2 lymphadenectomy has been a standard of treatment for stage III gastric cancer, there is no established chemotherapy for patients with recurrence during or within six months after the completion of adjuvant docetaxel plus S-1 therapy.Methods: The OGSG 1901 trial is a prospective, open-label, multicenter, phase II trial evaluating ramucirumab plus irinotecan for gastric cancer patients with early relapse after adjuvant docetaxel plus S-1 therapy. The key eligibility criteria were: 1) histologically confirmed gastric adenocarcinoma 2) patients who were on docetaxel plus S-1 adjuvant chemotherapy after the confirmation of pathological stage III, 3) patients with early relapse, i.e., recurrence during or within 6 months after the completion of docetaxel plus S-1 therapy, and 4) patient with Eastern Cooperative Oncology Group performance status of 0-1. Irinotecan (150 mg/m2, day 1) and ramucirumab (8 mg/kg, day 1) will be administered every 2 weeks. The primary endpoint is overall survival, and the secondary endpoints are overall response rate, progression-free survival, and safety. The number of patients has been set at 40 based on the threshold and expected median survival times of 7 and 11 months, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods are 2 and 1.5 years, respectively.Discussion: The results of this trial will indicate whether the ramucirumab with irinotecan regimen has the potential to be a recommended treatment regimen for patients with recurrence gastric cancer during or within 6 months after the completion of adjuvant docetaxel plus S-1 therapy.Trial Registration: This study was registered in the Japan Registry of Clinical Trials ( jRCTs05119071 , October 6, 2019). [ABSTRACT FROM AUTHOR]

Background and Aim: A multicenter randomized controlled trial reported a better R0 resection rate for intermediate‐sized (10–20 mm) colorectal polyps with underwater endoscopic mucosal resection (UEMR) than conventional endoscopic mucosal resection (CEMR). To clarify whether UEMR removes enough submucosal tissue in the removal of unpredictable invasive cancers, we investigated the cutting plane depth with UEMR versus CEMR. Methods: This was a post‐hoc analysis of a randomized controlled trial in which 210 intermediate‐sized colorectal polyps were removed in five Japanese hospitals. One pathologist and two gastroenterologists independently reviewed all resected specimens and measured the cutting plane depth. The cutting plane depth was evaluated as (i) maximum depth of submucosal layer and (ii) mean depth of submucosal layer, calculated using a virtual pathology system. Results: We identified 168 appropriate specimens for the evaluation of the cutting plane depth, resected by UEMR (n = 88) and CEMR (n = 80). The median resection depth was not significantly different between UEMR and CEMR specimens, regardless of the measurement method ([i] 1317 vs 1290 μm, P = 0.52; [ii] 619 vs 545 μm, P = 0.32). All specimens in the UEMR and CEMR groups contained substantial submucosa and no muscularis propria. Conclusions: The cutting plane depth with UEMR was comparable with that with CEMR. UEMR can be a viable alternative method that adequately resects the submucosal layer for the histopathological assessment of unpredictable submucosal invasive cancers. [ABSTRACT FROM AUTHOR]

Objectives: The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. Methods: In this multicenter observation study, GC and non‐GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura–Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. Results: Overall, 115 GC and 265 non‐GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5–5.3]), high EGGIM score (OR 1.8 [1.0–3.1]) and opened‐type Kimura–Takemoto (OR 2.5 [1.4–4.5]) had significant associations with GC risk. In the Kyoto classification, opened‐type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image‐enhanced endoscopy, and map‐like redness in the corpus were independent high‐risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). Conclusions: The OLGIM stage III/IV, high EGGIM score and open‐typed Kimura–Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023). [ABSTRACT FROM AUTHOR]

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ). [ABSTRACT FROM AUTHOR]

Background: To assure the equivalence between new clinical measurement methods and the standard methods, the four-quadrant plot and the plot's concordance rate is used in clinical practice, along with Bland-Altman analysis. The conventional concordance rate does not consider the correlation among the data on individual subjects, which may affect its proper evaluation.Methods: We propose a new concordance rate for the four-quadrant plot based on multivariate normal distribution to take into account the covariance within each individual subject. The proposed concordance rate is formulated as the conditional probability of the agreement. It contains a parameter to set the minimum concordant number between two measurement methods, which is regarded as agreement. This parameter allows flexibility in the interpretation of the results.Results: Through numerical simulations, the AUC value of the proposed method was 0.967, while that of the conventional concordance rate was 0.938. In the application to a real example, the AUC value of the proposed method was 0.999 and that of the conventional concordance rate was 0.964.Conclusion: From the results of numerical simulations and a real example, the proposed concordance rate showed better accuracy and higher diagnosability than the conventional approaches. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21–1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3–10). Median survival time was 19 days (range, 3–657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8–1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aimed to compare contrast‐enhanced harmonic endoscopic ultrasound (CH‐EUS) with fundamental B‐mode endoscopic ultrasonography (EUS) and contrast‐enhanced computed tomography (CE‐CT) for the diagnosis of left hepatic lobe metastases of pancreatic adenocarcinoma. Methods: In this single‐center prospective study, CE‐CT, EUS, and CH‐EUS were performed to detect left hepatic lobe metastases in patients with pancreatic adenocarcinoma, and the detection rates were compared between EUS plus CH‐EUS and the other two modalities. Subgroup comparisons of between‐modality detection rate were performed in patients with only metastases of <10 mm. The number of pancreatic adenocarcinoma patients whose clinical stage and treatment strategy were changed because of EUS plus CH‐EUS findings was also assessed. Results: Thirty‐one patients were diagnosed with left hepatic lobe metastases. For overall detection of left hepatic lobe metastases, EUS plus CH‐EUS had significantly higher accuracy (94.3%) than CE‐CT (86.7%) and EUS alone (87.6%) (P = 0.021 and P = 0.020, respectively). For detection of left hepatic lobe metastases < 10 mm, EUS plus CH‐EUS (93.3%) was significantly superior to CE‐CT (84.4%) and EUS alone (85.6%) (P = 0.021 and P = 0.020, respectively). In five of the 11 patients in whom only CH‐EUS allowed detection of hepatic metastases, the stage and/or treatment strategy of the pancreatic adenocarcinoma was changed after CH‐EUS. Conclusion: This study demonstrated that EUS plus CH‐EUS has advantages over CE‐CT and EUS alone with regard to the accuracy of detecting left hepatic lobe metastases, particularly small hepatic metastases and accurate staging. [ABSTRACT FROM AUTHOR]

Objectives: This single‐center comparative randomized superiority study compared biliary stenting using fully covered self‐expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo‐adjuvant chemotherapy (NAC). Methods: Twenty‐two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab‐paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re‐interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. Results: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re‐interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. Conclusions: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473). [ABSTRACT FROM AUTHOR]

Background: To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin (SP). Methods: Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m2, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m2, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m2, days 1, 15, S-1; 80 mg/m2, days 1–21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m2, day1, 8, S-1; 80 mg/m2, days 1–14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety. Results: From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months, p = 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups. Conclusions: There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy. [ABSTRACT FROM AUTHOR]

There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P < 0.001). RR (25.6% versus 7.7%, P = 0.065) were higher in the PTX group than in the DTX group. Compared to the PTX group, neutropenia (28% versus 80%) and leukopenia (28% versus 76%) of grade ≥3 as well as febrile neutropenia (0% vs. 46%, P < 0.0001) occurred more frequently in the DTX group. PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. UMIN000007940. • This study is the first to compare PTX to DTX in ESCC in second-line setting. • PTX showed significantly better efficacy as well as less toxicity than DTX. • Our data suggested the validity of PTX as second-line therapy was not reliant on ICI. [ABSTRACT FROM AUTHOR]

Background: We investigated the most effective suction pressure for preventing or promptly improving postoperative air leaks on digital drainage devices after lung resection.Methods: We retrospectively analyzed the postoperative data of 242 patients who were monitored with a digital drainage system after pulmonary resection in our institution between December 2017 and June 2020. We divided the patients into three groups according to the suction pressure used: A (low-pressure suction group: - 5 cm H2O), B (intermediate-pressure group: - 10 cm H2O), and C (high-pressure suction group: - 20 cm H2O). We evaluated the duration of air leaks, timing of chest tube replacement, the amount of postoperative air leak, volume of fluid drained before chest tube removal, and the total number of air leaks during drainage.Results: In total, 217 patients were included in this study. The duration of air leaks gradually decreased with significant difference between the groups, the highest decrease in A, the lowest decrease in C (P = 0.019). Timing of chest tube replacement, on the other hand, did not significantly differ between the three groups (P = 0.126). The number of postoperative air leaks just after surgery did not significantly differ between the three groups (P = 0.175), but the number of air leaks on postoperative day 1 were fewest in group A, then B, and greatest in group C (P = 0.033). The maximum amount of air leaks during drainage was lowest in A, then B, and highest in C (P = 0.036). Volume of fluid drained before chest tube removal did not significantly differ between the three groups (P = 0.986).Conclusion: Low-pressure suction after pulmonary resection seems to avoid or promptly improve postoperative air leaks in digital drainage devices after lung resection.Trial Registration: This is a single-institution, retrospective analysis-based study of data from an electronic database. Study protocol was approved by the Akashi Medical Center Institutional Research Ethics Board (approval number: 2020-9). [ABSTRACT FROM AUTHOR]

The relevance of pregestational body mass index (BMI) on adverse pregnancy outcomes remained unclear in Southwest China. This study aimed to investigate the overall and age-category specific association between pre-gestational BMI and gestational diabetes mellitus (GDM), preeclampsia, cesarean delivery, preterm delivery, stillbirth, macrosomia, and small-for-gestational age (SGA) or large-for-gestational age (LGA) neonates in Southwest China. Furthermore, it explores the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. 51,125 Chinese singleton pregnant women were recruited as study subjects. Multiple logistic regression models were used to examine the influence of pre-pregnancy BMI on adverse pregnancy outcomes. Gradient boosting machine was used to evaluate the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. It is found that women who were overweight or obese before pregnancy are at higher risk of adverse pregnancy outcomes except for SGA neonates, while pre-pregnancy underweight is a protective factor for GDM, preeclampsia, cesarean delivery, macrosomia and LGA, but not SGA. Younger mothers are more susceptible to GDM and macrosomia neonates, while older mothers are more prone to preeclampsia. Pre-pregnancy BMI has more influence on various pregnancy outcomes than maternal age. To improve pregnancy outcomes, normal BMI weight as well as relatively young maternal ages are recommended for women in child-bearing age. [ABSTRACT FROM AUTHOR]

Background: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. Methods: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80–120 mg on days 1–14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80–120 mg on days 1–21, every 5 weeks). The primary endpoint was overall survival (OS). Results: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2–49) with DS and 5.5 (range 1–10) with CS. There were no treatment-related deaths. The most common grade 3–4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337–1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). Conclusions: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials. [ABSTRACT FROM AUTHOR]