A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study).

Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

Risk factors and treatment strategies for cholecystitis after metallic stent placement due to malignant biliary obstruction: a multicenter retrospective study.

BACKGROUND AND STUDY AIMS: Cholecystitis can occur after self-expandable metallic stent (SEMS) placement for malignant biliary obstructions (MBO). Furthermore, the best treatment option for cholecystitis has not been determined. Here, we aimed to identify the risk factors of cholecystitis after SEMS placement and determine the best treatment option. PATIENTS AND METHODS: Incidence, treatments, and predictive factors of cholecystitis were retrospectively evaluated in 1,084 patients with distal MBO (DMBO) and 353 patients with hilar MBO (HMBO) who underwent SEMS placement at the 12 institutions from January 2012 to March 2021. RESULTS: Cholecystitis occurred in 7.5% of patients with DMBO and 5.9% of patients with HMBO. The recurrence rate was significantly lower (p=0.043), and the recurrence-free period was significantly longer (p=0.039) in endoscopic procedures than in percutaneous procedures for cholecystitis treatment. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) was better in terms of technical success, procedure time, and recurrence-free period than endoscopic transpapillary gallbladder drainage. The cases with obstruction across the cystic duct orifice by tumor (p=0.015) and those with obstruction by stent (p=0.037) were the independent risk factors for cholecystitis in DMBO. The cases with multiple SEMS placements (OR 11, 95% CI 0.68-190, p=0.091) and those with gallbladder stones (OR 2.3, 95% CI 0.92-5.6, p=0.075) had a higher risk for cholecystitis in HMBO. CONCLUSIONS: The incidences of cholecystitis after SEMS placement for DMBO and HMBO were comparable. EUS-GBD is the optimal treatment option for patients with cholecystitis after SEMS placement for MBO.

Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses.

Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation.

OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.

Epidural versus patient-controlled intravenous analgesia on pain relief and recovery after laparoscopic gastrectomy for gastric cancer: randomized clinical trial.

BACKGROUND: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG. METHODS: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia. RESULTS: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event. CONCLUSIONS: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm).

Lymphatic venous anastomosis and complex decongestive therapy for lymphoedema: randomized clinical trial.

BACKGROUND: Lymphatic venous anastomosis is associated with a low incidence of lower extremity lymphoedema-associated cellulitis; however, the exact relationship is unknown. This multicentre RCT evaluated the effect of lymphatic venous anastomosis on prevention of cellulitis. METHODS: Patients with secondary lower extremity lymphoedema who underwent at least 3 months of non-operative decongestive therapy were assigned randomly to lymphatic venous anastomosis or conservative therapy. The primary and secondary outcomes were cellulitis frequency, and assessments of circumference, hardness, and pain respectively. RESULTS: Overall, 336 patients were divided into two groups: 225 in the full-analysis set (primary outcome 225; secondary outcomes 170) and 156 in the per-protocol set (primary outcome 156; secondary outcomes 110). In both analyses, lymphatic venous anastomosis with non-operative decongestive therapy was more effective in preventing cellulitis than non-operative decongestive therapy alone; the difference between groups in reducing cellulitis frequency over 6 months was -0.35 (95 per cent c.i. -0.62 to -0.09; P = 0.010) in the full-analysis set (FAS) and -0.60 (-0.94 to -0.27; P = 0.001) in the per-protocol set (PPS) Limb circumference and pain were not significantly different, but lymphatic venous anastomosis reduced thigh area hardness (proximal medial and distal and lateral proximal). Four patients experienced contact dermatitis with non-operative decongestive therapy alone. CONCLUSION: Lymphatic venous anastomosis in combination with non-operative decongestive therapy prevents cellulitis. REGISTRATION NUMBER: UMIN00025137, UMIN00031462.

Prospective evaluation of core number of biopsy for renal tumor: are multiple cores preferable?

PURPOSE: This single-center, single-arm, prospective, open-label study was conducted to evaluate the optimal number of cores (single or multiple) in renal tumor biopsy. MATERIALS AND METHODS: Forty-four biopsies of 44 tumors (mean diameter, 2.7 ± 1.0 cm; range, 1.6-5.0 cm) were included. Biopsy was performed under ultrasound or computed tomography fluoroscopy guidance using an 18-gauge cutting needle and the co-axial method. Two or more specimens were obtained, which were divided into first and subsequent specimens. "First specimen" and "all specimens" were histologically evaluated (i.e., appropriateness of specimen, histological diagnosis, subtype, and Fuhrman grade of renal cell carcinoma [RCC]) blindly and independently by two board-certified pathologists. RESULTS: Multiple specimens were successfully and safely obtained in all the biopsies. All tumors were histologically diagnosed; 40 malignancies included 39 RCCs and 1 solitary fibrous tumor, and 4 benign lesions included 2 angiomyolipomas, 1 oncocytoma, and 1 capillary hemangioma. In all RCCs, the subtype could be determined (32 clear cell RCCs, 4 chromophobe RCCs, and 3 papillary RCCs), and the Furman grade was determined in 38 RCCs. When only the first specimen was evaluated, 22.7% of the specimens were inappropriate for diagnosis, and 34 (77.3%) were histologically diagnosed. The diagnostic yield was significantly lower than that of all specimens (P = 0.0044). Univariate analysis revealed that smaller lesions were a significant predictor of diagnostic failure (P = 0.020). CONCLUSION: Biopsy with multiple cores significantly improved diagnostic yield. Thus, operators should obtain multiple cores during renal tumor biopsy.

Results of the interim analysis of a prospective, multicenter, observational study of small subepithelial lesions in the stomach.

OBJECTIVES: Long-term outcomes of gastric subepithelial lesions have not been elucidated. To reveal the natural history, we initiated a prospective, 10-year follow-up of patients with small (≤20 mm) gastric subepithelial lesions in September 2014. Here, we report the results of an interim analysis of a prospective observational study. METHODS: In total, 567 patients with 610 lesions were prospectively registered between September 2014 and August 2016. The location, size, morphology, and number of subepithelial lesions were recorded on a web-based case report form. This study has been conducted as an Academic Committee Working Group of the Japan Gastroenterological Endoscopy Society. RESULTS: The endoscopic follow-up period was 4.60 ± 1.73 years (mean ± standard deviation), and survival data were investigated for 5.28 ± 1.68 years. This interim analysis revealed that the estimated cumulative incidence of a size increase ≥5 mm, after accounting for patients' death and resection of the tumor as competing risk events, was 4.5% at 5 years. In addition, the estimated cumulative incidence of lesion size increase ≥5 mm or resection of lesions was 7.9% at 5 years, and that of size increase ≥10 mm or resection of lesions was 4.5% at 5 years. CONCLUSION: These results indicate that approximately one in 13 patients with small (≤20 mm) gastric subepithelial lesions may require resection or further investigation for increased tumor size (≥5 mm) within 5 years.

Complementary and Alternative Medicine Use, Cancer Screening, and Medical Checkups in Japan from 2001 to 2013: A Repeated Cross-Sectional Study.

Introduction: The association between complementary and alternative medicine (CAM) use and other health-related behaviors is an important issue. A previous study reported that complementary medicine use is related to greater use of cancer screening, whereas alternative medicine use is related to lower use of cancer screening. Given the sparse evidence from Japan, we aimed to examine the association of CAM use with cancer screening and medical checkups. We used a repeated cross-sectional survey of a nationally representative sample of Japanese people and conducted age-period-cohort analysis. Methods: The study population was 68,217 of 83,827 individuals observed from 2001 to 2013 who received cancer screening. CAM users were defined as individuals who received acupuncture, moxibustion, anma/massage/shiatsu, or judo therapy for their most worrisome symptom. The outcomes of interest were receiving stomach, lung, colorectal, uterine, and breast cancer screenings and medical checkups. Using crossclassified multilevel logistic regression models, we estimated odds ratios (ORs) and 95% credible intervals (CIs) for cancer screening and medical checkups. Results: For CAM users of complementary medicine, the adjusted ORs for stomach, lung, and colorectal cancer screening were 1.40 (95% CI: 1.35-1.44), 1.37 (95% CI: 1.34-1.40), and 1.52 (95% CI: 1.49-1.54), respectively. We found similar results for uterine and breast cancer screening, and medical checkups. Conclusions: Irrespective of whether they use CAM, CAM users in Japan tend to receive a variety of cancer screenings and medical checkups.

Factors associated with survival in patients with clear cell sarcoma.

Aims: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection.

BACKGROUND: Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. METHODS: This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or no-teprenone groups in a 1:1 ratio. We stratified patients by sex, age < and ≥ 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. RESULTS: One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). CONCLUSION: Teprenone afforded no clinical benefit. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs061200002 (registered on 20/May/2020).

A population-based longitudinal study on glycated hemoglobin levels and new-onset chronic kidney disease among non-diabetic Japanese adults.

Chronic kidney disease (CKD) is a major global public health problem. Recent studies reported that diabetes and prediabetes are risk factors for developing CKD; however, the exact glycated hemoglobin (HbA1c) cut-off value for prediabetes remains controversial. In this study, we aimed to examine the relationship between HbA1c levels and subsequent CKD development in greater detail than previous studies. Longitudinal data of annual checkups of 7176 Japanese non-diabetic people (male: 40.4%) from 1998 to 2022 was analyzed. HbA1c values were categorized into < 5.0%, 5.0-5.4%, 5.5-5.9%, and 6.0-6.4%. CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. The descriptive statistics at study entry showed that higher HbA1c values were associated with male, older, overweight or obese, hypertensive, or dyslipidemic people. During a mean follow-up of 7.75 person-years, 2374 participants (male: 40.0%) developed CKD. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. The adjusted time ratios of developing CKD for HbA1c levels of 5.5-5.9% and 6.0-6.4% compared with 5.0-5.4% were 0.97 (95% confidence interval: 0.92-1.03) and 1.01 (95% confidence interval: 0.90-1.13), respectively. There was no association between HbA1c in the prediabetic range and subsequent CKD development.

Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program.

BACKGROUND: We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program. METHODS: Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test. RESULTS: During the follow-up, 19 cases of gastric cancer were detected. By Kaplan-Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99-171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58-49.8, and the ABC method (method 2); 7.52, 2.49-22.7). CONCLUSIONS: Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program.

Characteristics of synchronous and metachronous duodenal tumors and association with colorectal cancer: a supplementary analysis.

BACKGROUND: We previously reported outcomes of endoscopic resection for duodenal tumors in a large cohort. This study investigated the frequency and characteristics of synchronous and metachronous lesions, and their association with colorectal advanced adenoma (CAA) and colorectal cancer (CRC). METHODS: Patients underwent duodenal endoscopic resection during January 2008 to December 2018. Background and characteristics, incidence of synchronous and metachronous lesions, and incidence of CAA and CRC were investigated. Patients without synchronous lesions were classified as the single group, and those with synchronous lesions as the synchronous group. Patients were also classified as the metachronous and non-metachronous groups. The characteristics among the groups were compared. RESULTS: We included 2658 patients with 2881 duodenal tumors: 2472 (93.0%) patients had single, 186 (7.0%) had synchronous, and 54 (2.0%) had metachronous lesions. The 5-year cumulative incidence of metachronous lesions was 4.1%. In total, 208 (7.8%) had CAA and 127 (4.8%) patients had CRC, and colonoscopy was performed in 936 (35.2%) patients. The incidence of CAA in the synchronous groups tended to be higher compared with that in the single groups (11.8% vs 7.5%, adjusted risk ratio 1.56), and the incidence of CRC in the metachronous groups tended to be higher compared with that in the non-metachronous groups (13.0% vs 4.6%, adjusted risk ratio 2.75), but there was no difference after adjusting for colonoscopy. CONCLUSIONS: This study showed the incidence of synchronous and metachronous duodenal lesions. There was no significant difference in incidence of CAA and CRC among each group, but further studies are warranted.

Protocol for a randomised, placebo-controlled, double-blinded clinical trial on the effect of oestrogen replacement on physical performance to muscle resistance exercise for older women with osteoarthritis of knee joint: the EPOK trial.

BACKGROUND: Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA. METHODS: We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat. DISCUSSION: The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs061210062. Registered 17th December 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs061210062 .

Frailty and all-cause and cause-specific mortality in Japan.

BACKGROUND: In aging societies, there is an increasing focus on the concept of frailty. However, there is no consistent means to assess this concept. We assessed frailty using the Kihon Checklist (KCL), which is widely used in Japan, and examined the association between frailty and all-cause and cause-specific mortality in Japan, the most aged society in the world. METHODS: This was a retrospective cohort study, and we analyzed 43,312 participants aged ≥ 65 years who were enrolled in basic health checkups in Okayama City, Japan. We defined the frailty status of the participants using the KCL. To assess the association of frailty status with all-cause and cause-specific mortality, we used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs), adjusting for individual potential confounders. Mean follow-up time was 9.3 years. RESULTS: The fully adjusted HR for all-cause mortality was 1.34 (95% confidence interval [CI]: 1.27-1.41) for the prefrail group and 2.22 (95% CI: 2.11-2.33) for the frail group. A similar pattern was observed for cardiovascular disease, respiratory disease, and cancer mortality. Younger people (65-74 years) and women tended to have higher effect estimates than older people (≥ 75 years) and men. CONCLUSION: Prefrailty and frailty can increase the risk of both all-cause and cause-specific mortality. Our study suggests that to support frail patients, it could be effective to focus on the prevention and management of cardiovascular and respiratory disease, and that the KCL may be useful as a method of screening for frailty.

Breastfeeding at 6 months of age had a positive impact on overweight and obesity in Japanese adolescents at 15 years of age.

AIM: A number of studies have indicated the potential benefits that breastfeeding has on reducing childhood obesity, but few studies have evaluated the effect on adolescent obesity. We examined the association between breastfeeding and overweight or obesity at 15 years of age using data from a large nationwide longitudinal study launched by the Japanese Government in 2001. METHODS: We analysed data for 26 164 participants with known infant feeding practices at 6 months of age, namely the duration of breastfeeding or formula feeding. Overweight or obesity at 15 years of age were calculated based on the subject's self-reported height and weight. Multinomial logistic regression analysis adjusted the data for child factors, namely sex, siblings, birth weight and physical activity clubs and the maternal factors of age, educational attainment and smoking status. RESULTS: Formula feeding was associated with an increased risk of overweight or obesity at 15 years of age. The adjusted odds ratios (95% confidence intervals) were 0.99 (0.89-1.09) for partial breastfeeding and 1.23 (1.02-1.48) for formula feeding, when exclusive breastfeeding was the reference category. CONCLUSION: Breastfeeding during infancy had potential benefits for overweight or obesity among 15-year-old adolescents. Our results provide further evidence of the importance of breastfeeding.

Bilateral verses bilateral with tri-segmental endoscopic drainage using metal stents for high-grade malignant hilar biliary obstructions: A multicenter, randomized controlled trial: BRAVE study (BRAVE study).

INTRODUCTION: Bilateral endoscopic drainage with self-expanding metallic stent (SEMS) can be used to manage hilar malignant biliary obstruction (HMBO) more effectively in comparison to unilateral drainage. An increased drainage area is predicted to prolong stent patency and patient survival. However, few reports have described the utility of trisegmental drainage and the benefits of using trisegmental drainage remain unknown. Thus, we launched a randomized clinical trial (RCT) to compare the clinical outcomes between bilateral and trisegmental drainage using SEMSs in patients with high-grade HMBO. METHODS AND ANALYSIS: This study was conducted as a multicenter randomized control trial (RCT) in 8 high-volume medical centers in Japan, and will prove the non-inferiority of bilateral drainage to trisegmental drainage. Patients with unresectable HMBO with Bismuth type IIIa or IV who pass the inclusion and exclusion criteria will be randomized to receive bilateral or trisegmental drainage at a 1:1 ratio. At each center, the on-site study investigators will obtain informed consent from the candidates, and will use an electronic data capture system (REDCap) to input necessary information, and register candidates with the registration secretariat. The primary endpoint is the rate of non-recurrent biliary obstruction (RBO) at 180 days after SEMSs placement. A -10% non-inferiority margin is assumed in the statistical analysis of the primary endpoint. Secondary endpoints include the rate of technical and clinical success, time to recurrent biliary obstruction (TRBO), causes of RBO, procedure-related adverse events (AEs), procedure time, TRBO with or without endoscopic sphincterotomy, overall survival, and the technical and clinical success rates at reintervention. DISCUSSION: If the non-inferiority of bilateral drainage is demonstrated, it is predicted that the procedure time will be shortened and the medical cost will be reduced, which will be beneficial to the patient and the medical economy. TRIAL REGISTRATION: Registered in Japan Registry of Clinical Trial-Registration (trial number. jRCTs062220038). This version number 1. Protocol dated Jun 23, 2022.

Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resection.

Background and study aims Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens. Patients and methods Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9 mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues. Results Forty polyps resected via CSP (n = 14), HSP (n = 12), or UEMR (n = 14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57 % and 29 % for CSP, 92 % and 83 % for HSP, and 100 % and 100 % for UEMR, respectively ( P  = 0.005 for MM and P  < 0.001 for SM tissue). Multiple logistic regression analysis showed UEMR was an independent factor relating to the containment of SM tissue. The thickness of SM tissue by CSP, HSP, and UEMR were 52 µm, 623 µm, and 1119 µm, respectively ( P  < 0.001). The thickness by CSP was significantly less than those by HSP and UEMR ( P  < 0.001, Bonferroni correction). Conclusions UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps.