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Abstract Many studies conducted after the COVID-19 pandemic have examined the relationship between changes in social traits, such as attractiveness and wearing face masks. However, most studies examine the effect of wearing face masks at a single time point, and the time effect is not known. Additionally, few studies address wearing sunglasses, another facial occluding item. This study examined the effects of facial occluding (unoccluded face, face masks, sunglasses, or both) on perceived attractiveness, trustworthiness, and familiarity at two time points, September 2020, six months after the start of the COVID-19 pandemic, and April 2022, almost two years later, using Japanese higher and lower attractive faces. Results showed that only lower attractive faces wearing face masks had a time effect on attractiveness and familiarity and no time effect on social traits in higher attractive faces. Perceived all social traits were the highest for unoccluded faces, and faces wearing face masks had the same level of attractiveness and familiarity as unoccluded faces. Perceived trustworthiness was higher for unoccluded faces, faces wearing face masks, sunglasses, and both sunglasses and face masks, respectively. Additionally, faces wearing both sunglasses and face masks had the lowest perceived all social traits. These findings suggest that the positive and time effects of wearing face masks are limited in Japan, suggesting a greater positive impact of unoccluded faces. They also suggest that the negative impact of wearing sunglasses is significant.

Background: Neoadjuvant chemotherapy is standard for advanced esophageal squamous cell carcinoma, though often ineffective. Therefore, predicting the response to chemotherapy before treatment is desirable. However, there is currently no established method for predicting response to neoadjuvant chemotherapy. This study aims to build a deep-learning model to predict the response of esophageal squamous cell carcinoma to preoperative chemotherapy by utilizing multimodal data integrating esophageal endoscopic images and clinical information., Methods: 170 patients with locally advanced esophageal squamous cell carcinoma were retrospectively studied, and endoscopic images and clinical information before neoadjuvant chemotherapy were collected. Endoscopic images alone and endoscopic images plus clinical information were each analyzed with a deep-learning model based on ResNet50. The clinical information alone was analyzed using logistic regression machine learning models, and the area under a receiver operating characteristic curve was calculated to compare the accuracy of each model. Gradient-weighted Class Activation Mapping was used on the endoscopic images to analyze the trend of the regions of interest in this model., Results: The area under the curve by clinical information alone, endoscopy alone, and both combined were 0.64, 0.55, and 0.77, respectively. The endoscopic image plus clinical information group was statistically more significant than the other models. This model focused more on the tumor when trained with clinical information., Conclusions: The deep-learning model developed suggests that gastrointestinal endoscopic imaging, in combination with other clinical information, has the potential to predict the efficacy of neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma before treatment., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethics statements: Approval of the research protocol by an Institutional Reviewer Board: This study was reviewed and approved by the Institutional Ethics Review Board (approval no. 2023-1-046). Informed consent: The study was a backward-looking examination of clinical findings and did not involve direct intervention. Therefore, informed consent was not taken, but information was disclosed instead. Information disclosure materials approved by the Ethics Committee were posted on the Tohoku University Graduate School of Medicine website to ensure that research subjects or their proxies had the opportunity to refuse participation. Registry and Registration No. of the study/trial: UMIN000031874. Animal Studies: N/A., (© 2025. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Frailty assessment is essential for deciding the treatment strategy for patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Recently, the revised Japanese version of the Cardiovascular Health Study (J-CHS) criteria has been proposed for the frailty assessment; however, it is unclear whether the criteria are useful for the risk stratification in these patients. We investigated the impact of frailty assessment using the revised J-CHS criteria on clinical outcomes in patients with AS undergoing TAVR. We examined 205 consecutive severe AS patients who underwent TAVR at two tertiary hospitals from May 2018 to December 2022. Frailty was defined by the revised J-CHS criteria (score ≥ 3) before TAVR. The primary outcome was major adverse cardiac or cerebrovascular events (MACCE). Among the studied patients, the mean age was 84 years and 65% were female. Frailty was present in 51% of patients. During a median follow-up period of 1000 (interquartile range 677-1210) days, MACCE occurred in 22 patients. Frailty was significantly independently associated with higher risks of the MACCE adjusted for confounders related to nutritional status, severity of AS, comorbidities [hazard ratio (HR) 5.09, 95% confidence interval (CI) 1.70-15.23; HR 3.94, 95% CI 1.34-11.55; HR 3.12, 95% CI 1.14-8.53; HR 3.31, 95% CI 1.21-9.02, respectively]. Frailty determined by the revised J-CHS criteria was associated with clinical outcomes, suggesting these criteria would be useful for risk stratification in Japanese patients with AS undergoing TAVR., Competing Interests: Declarations. Conflict of interest: There is no financial conflict of interest relating to the present study to disclose. Ethical approval: This study was approved by Hokkaido University Hospital Review Board (019-0132)., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) tumor thrombus is generally considered to be borderline resectable because of its poor prognosis. 1-5 This report describes a patient who underwent multidisciplinary treatment for HCC with massive IVC tumor thrombus., Methods: The 56-year-old woman in this study had diffuse HCC of the medial and anterior segments. She received an explanation of the procedure and provided informed consent. A tumor thrombus was observed in the right atrium through the middle and left hepatic veins and in the anterior branch of the portal vein. The HCC was considered unresectable, and atezolizumab plus bevacizumab combination therapy was initiated. However, the tumor thrombus progressed to the right atrium after two courses. The treatment was changed to hepatic arterial infusion chemotherapy with cisplatin and three-dimensional conformal radiotherapy to the tumor thrombus in the right atrium, followed by systemic lenvatinib., Results: The patient's tumor marker levels decreased significantly, and the tumor thrombus regressed into the IVC. Left hepatic trisegmentectomy and IVC tumor thrombectomy were performed. 6-8 Although Clavien-Dindo IIIa postoperative biliary leakage was observed, the patient was discharged on postoperative day 56. Pathologic findings showed no viable residual tumor cells in either the main tumor or the tumor thrombus, and the patient had a pathologic complete response. At this writing, the patient has been recurrence-free for 19 months since the initial treatment without any adjuvant therapy., Conclusion: This report presents a case of unresectable HCC treated with multimodality therapy followed by salvage surgery. The patient achieved a long-term cancer-free and drug-free status through aggressive treatment. This patient's experience offers hope for aggressive treatment of advanced HCC., Competing Interests: Disclosure: The authors declare that they have no conflicts of interest and received no funding support for this research. Informed consent: The patient received an explanation of the procedure and provided their informed consent., (© 2024. Society of Surgical Oncology.)

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants that have been used for various purposes. Although PFAS can pollute the environment in a variety of areas related to the use, storage, and disposal of their products, there are insufficient data on the extent of PFAS pollution outside industrialized countries with their manufacturing facilities. Most of the analyses depend on high-cost liquid chromatography-tandem mass spectrometry. In this study, we established a method to analyze ionic PFAS using gas chromatography-electron impact ionization-mass spectrometry with in-port arylation by diaryl iodonium. Extraction of PFAS from water samples was performed using solid phase extraction with reverse phase sorbent. Fourteen PFAS compounds could be detected from spiked water samples, and the detection limit ranged from 3.1 to 8.1 ng L -1 . Using this method, we analyzed groundwater samples from Okinawa Island, Japan, and detected PFAS up to a total concentration of 1900 ng L -1 . This method uses relatively inexpensive analytical equipment; hence, it can possibly enable surveys on PFAS contaminations in a wide range of regions and opportunities., Competing Interests: Declarations. Ethical approval: Not applicable Consent to participate: Not applicable Consent for publication: Not applicable Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC). However, monitoring the progression status of AR-negative prostate cancer is a challenge because it does not produce prostate-specific antigen. Based on the negative relationship of expression between AR and SSEA-4, we hypothesized that a soluble molecule synchronized with SSEA-4 in expression could be a serum marker candidate for AR-negative prostate cancer. Thus, we investigated the molecular background of SSEA-4 expression by ST3GAL2-knockout in DU145 cells. Here we show that MUC1 is identified as a molecule associated with ST3GAL2 and expressed in AR-negative prostate cancer. A negative correlation of expression between AR and MUC1 was observed in prostate cancer cell lines and CRPC tissues. The average rate of MUC1 expression was nearly 60% in AR-negative prostate cancer cells in CRPC tissues. Level of serum CA15-3 (MUC1) was the highest in mCRPC among various stages and its higher level was associated with faster progression of mCRPC. Our results demonstrate that MUC1 is identified as a ST3GAL2-associated molecule and expressed in AR-negative CRPC cells. Furthermore, level of serum CA15-3 may reflect the progression status of mCRPC., Competing Interests: Declarations. Competing interests: One of the authors (K. T.) received young investigator research grant (BASJ20210426034) from Bayer Pharma Japan. Ethics approval: This study was approved by the Ethics Committee of the University of the Ryukyus, Naha City Hospital, Chubu Tokushukai Hospital, and Yamagata Prefectural Central Hospital (No. 524) in accordance with the Declaration of Helsinki principle. Informed consent was obtained from each patient by opt-in or patients were given the opportunity to refuse participation by opt-out. Registry and the Registration No. of the study/trial: N/A. Animal studies: N/A., (© 2024. The Author(s).)

Background: Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated., Methods: The study enrolled 92 ICC patients who had undergone hepatic resection. Immunohistochemistry (IHC) assays were performed for TFR protein expression. The regulation of malignant activity and the effect on sensitivity to the ferroptosis-inducer artesunate by TFR were investigated in vitro., Results: Using IHC staining, 23 patients were categorized as TFR-positive. The TFR-positive group had a significantly larger tumor size and more microscopic vascular invasion. In the multivariate analysis, TFR positivity was an independent poor prognostic factor. In vitro TFR-knockdown (KD) significantly decreased the intracellular iron levels and the cell proliferation, migration, and invasion rates. Artesunate treatment significantly decreased cell viability, whereas cisplatin promoted ferroptosis. When iron transport into cells was inhibited by TFR-KD, ferroptosis was significantly suppressed. Expression of PD-L1 was induced by cisplatin, with a further increase observed when artesunate and cisplatin were used in combination., Conclusions: Transferrin receptor is a poor prognostic factor for ICC and contributes to sensitivity to ferroptosis., (© 2024. Society of Surgical Oncology.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by cerebrospinal fluid circulation disorders, and presents as gait and balance disturbances similar to those observed in other incurable neurological diseases. Although previous studies have reported deficits in bimanual coordination among patients with iNPH, these potential pathological characteristics have not received much attention to date. This study investigated the temporal characteristics of a bimanual finger-tapping task in patients with iNPH, focusing on within- and between-hand coordination., Methods: Study participants comprised three groups: patients with iNPH (N = 19, mean age = 76.9 ± 5.6 years), older adults (N = 19, 76.4 ± 5.3 years), and younger adults (N = 13, 32.2 ± 8.5 years). Participants performed a bimanual finger-tapping task under five conditions that manipulated the temporal differences between the two taps., Results: The iNPH group exhibited significantly greater errors in both within- and between-hand coordination tasks compared to the other two groups., Conclusion: These results suggest that assessing temporal errors in bimanual coordination tasks, particularly within-hand coordination, may be useful for uncovering pathological characteristics specific to iNPH., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of The Jikei University School of Medicine (Approval No.: 30–352 9373) and Tokyo Metropolitan University (Approval No.: H5-126). In conducting the research, we adhered strictly to the Personal Information Protection Law regarding the handling of personal information of the participants based on the Declaration of Helsinki. Consent to participate informed: Informed consent was obtained from all participants and/or their legal guardians. Consent for publication: Informed consent was obtained from all patients for the publication of anonymized data and findings obtained from this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Disclosures The authors declare that they have no conflict of interest.

Purpose: To compare image quality and diagnostic performance among SS-EPI diffusion weighted imaging (DWI), multi-shot (MS) EPI DWI, and reduced field-of-view (rFOV) DWI for muscle-invasive bladder cancer (MIBC)., Materials and Methods: This retrospective study included 73 patients with bladder cancer who underwent multiparametric MRI in our referral center between August 2020 and February 2023. Qualitative image assessment was performed in 73; and quantitative assessment was performed in 66 patients with maximum lesion diameter > 10 mm. The diagnostic performance of the imaging finding of muscle invasion was evaluated in 47 patients with pathological confirmation of MIBC. T2-weighted imaging, SS-EPI DWI, MS-EPI DWI, rFOV DWI, and dynamic contrast-enhanced imaging were acquired with 3 T-MRI. Qualitative image assessment was performed by three readers who rated anatomical distortion, clarity of bladder wall, and lesion conspicuity using a four-point scale. Quantitative assessment included calculation of SNR and CNR, and grading of the presence of muscle layer invasion according to the VI-RADS diagnostic criteria. Wilcoxon matched pairs signed rank test was used to compare qualitative and quantitative image quality. McNemar test and receiver-operating characteristic analysis were used to compare diagnostic performance., Results: Anatomical distortion was less in MS-EPI DWI, rFOV DWI, and SS-EPI DWI, in that order with significant difference. Clarity of bladder wall was greater for MS-EPI DWI, SS-EPI DWI, and rFOV DWI, in that order. There were significant differences between any two combinations of the three DWI types, except between SS-EPI DWI and MS-EPI in Reader 1. Lesion conspicuity, diagnostic performance, SNR and CNR were not significantly different among the three DWI types., Conclusions: Among the three DWI sequences evaluated, MS-EPI DWI showed the least anatomical distortion and superior bladder wall delineation but no improvement in diagnostic performance for MIBC. MS-EPI DWI may be considered for additional imaging if SS-EPI DWI is of poor quality., Competing Interests: Declarations Conflict of interest None. Ethical approval This retrospective cross-sectional study was approved by the Ethics Review Board of our institute. The study was performed per the ethical standards laid down in the 1964 Declaration of Helsinki. Informed consent The requirement to obtain informed consent for the study was waived due to its observational nature., (© 2024. The Author(s).)

Purpose: Lower-limb muscle mass reduction and fatty degeneration develop in patients with knee osteoarthritis (KOA) and could affect their symptoms, satisfaction, expectation and functional activities. The Knee Society Scoring System (KSS) includes patient reported outcome measures, which is widely used to evaluate the status of knee function of KOA. This study aimed to clarify how muscle mass and fatty degeneration of the lower limb correlate with the KSS in patients with KOA., Methods: This study included 43 patients with end-stage KOA, including nine males and 34 females. Computed tomography (CT) images of the lower limb obtained for the planning of total knee arthroplasty were utilized. Ten muscle groups were segmented using our artificial-intelligence-based methods. Muscle volume was standardized by dividing by their height squared. The mean CT value for each muscle group was calculated as an index of fatty degeneration. Bivariate analysis between muscle volume or CT values and KSS was performed using Spearman's rank correlation test. Multiple regression analysis was performed, and statistical significance was set at p  < 0.05., Results: Bivariate analysis showed that the functional activity score was significantly correlated with the mean CT value of all muscle groups except the adductors and iliopsoas. Multiple regression analysis revealed that the functional activities score was significantly associated with the mean CT values of the gluteus medius and minimus muscles and the anterior and lateral compartments of the lower leg (β = 0.42, p = 0.01; β = 0.33, p = 0.038; and β = 0.37, p = 0.014, respectively)., Conclusion: Fatty degeneration, rather than muscle mass, in the lower-limb muscles was significantly associated with functional activities score of the KSS in patients with end-stage KOA. Notably, the gluteus medius and minimus and the anterior and lateral compartments of the lower leg are important muscles associated with functional activities., (© 2024. The Author(s).)

Objective: The aim of this study was to assess the prevalence of peritumoral enhancement (PTE) in patients with muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) and to propose a modified diagnostic criterion for Vesical Imaging Reporting and Data System (VI-RADS) that incorporates PTE., Materials and Methods: This retrospective study included 95 patients with bladder cancer (age, 72 ± 11; 77 men; 36 MIBCs and 59 Non-MIBCs) who underwent multiparametric MRI in our referral center between 2011 and 2023. The images were interpreted by four radiologists. The readers classified the possibility of muscle layer invasion into categories 1-5, based on the VI-RADS categorical diagnostic criterion. PTE was defined as a linear contrast enhancement observed at the edge of tumor invasion which is convex outward from the normal bladder wall and contrasts more than the normal muscle layer and tumor. A modified VI-RADS that upgrades the final VI-RADS category to 4 if PTE is present when the original VI-RADS category is 3 or less was proposed. The frequency of PTE in the MIBC and NMIBC groups was compared using the Fisher's exact test. Sensitivity and specificity for the diagnosis of MIBC were compared with the original VI-RADS using McNemar test. Pathologic diagnosis was used as the reference standard., Results: PTE was present in 70-81% (25/36-29/36) of MIBC and absent in 92-98% (54/59-58/59) of non-MIBC. For all readers, the PTE was significantly more frequent (p < 0.001) in the MIBC group than the NMIBC group. The sensitivities of modified VI-RADS (75.0-86.1%) were significantly higher than those of original VI-RADS (41.7-55.6%) (p = 0.002-0.008). The specificity of modified VI-RADS (91.5-98.3%) were not statistically different from original VI-RADS (98.3-100%)., Conclusions: In conclusion, PTE is a highly specific finding for MIBC. modified VI-RADS incorporating PTE increases sensitivity for MIBC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Students with developmental disabilities are anxious about a change in environment when graduating from high school to college. Existing research, which is scarce, focuses on the mental health status of students with developmental disabilities entering university. This study investigated the frequency of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) among first-year Japanese university students and their mental health risks post-admission. We conducted a cross-sectional survey for university students within a month of admission, using the Autism Spectrum Quotient (AQ) and Adult ADHD Test (A-ADHD) to demonstrate the frequency of ASD and ADHD. The Counseling Center Assessment of Psychological Symptoms (CCAPS)-Japanese (depression, eating concerns, hostility, social anxiety, family distress, alcohol use, generalized anxiety, and academic distress) evaluated their mental health condition.Of 711 students (20.3 ± 2.1 years; 330 male, 381 female), the number of those showing either ASD or ADHD tendencies was 61 (8.58%). Twenty-three (3.23%) showed symptoms of only ASD, 34 (4.78%) of ADHD, and four (0.56%) of ASD and ADHD. No significant differences existed in the frequency of ASD and ADHD between each sex and major. The scores and frequency of high risk (over the cut-off points) students on all CCAPS-Japanese subscales (except alcohol use) were significantly higher among the ASD and ADHD groups than the control group, which showed no ASD or ADHD tendencies. The frequency of ASD and ADHD characteristics among first-year Japanese university students was 8.58%. They have a high risk of mental health problems when they enter university., (© 2024. The Author(s).)

Background: This study investigated the association between Phase Angle (PhA), measured by bioelectrical impedance analysis, and bleeding risk in hemodialysis patients to evaluate PhA as a predictive marker for bleeding events., Methods: This retrospective cohort study included 102 hemodialysis patients who underwent PhA measurements between July 2019 and April 2024. Demographic data, medical histories, dialysis parameters, and bleeding events were collected. Patients were stratified by PhA values and followed for a median of 832 days (IQR: 516-1304 days). Multivariate Cox proportional hazards regression and Kaplan-Meier analysis were performed., Results: The cohort had an average age of 74.0 years and a median dialysis vintage of 6.7 years. During follow-up, 19 patients (18.6%) experienced major bleeding events. Lower PhA was an independent risk factor for bleeding (HR: 0.24, 95% CI 0.11-0.52, p < 0.001). Kaplan-Meier analysis showed that patients with PhA ≥ 4.00 had a higher probability of remaining free from major bleeding at 2 years (94.3%) compared to those with PhA < 4.00 (75.0%) (p < 0.001). In 82 patients with repeat PhA measurements, bleeding event-free rates at 2 years were 97.5%, 75%, 100%, and 78.3% for the High to High, High to Low, Low to High, and Low to Low groups, respectively (p < 0.001)., Conclusion: PhA is a predictive marker for bleeding risk in hemodialysis patients. Routine PhA monitoring could help stratify bleeding risk and optimize clinical management., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: The information on the clinicopathologic/outcome differences between ampullary adenocarcinoma (AC) and pancreatic adenocarcinoma (PC) has been conflicting to the extent that it still is questioned whether ACs need to be recognized separately from PCs., Methods: The characteristics of 413 ACs were compared with those of 547 PCs., Results: The ACs had a better prognosis than the PCs (5-year survival, 57 % vs 23 %; p < 0.001). Even the pancreatobiliary (PB)-type ACs had a better prognosis (5-year survival, 46 % vs 23 %; p < 0.001). Several differences also were identified as contributing factors: (1) the preinvasive adenomatous component often constituted a significant proportion of the mass in ACs (>50 % of the tumor in 16 % vs 1.5 %; p < 0.001); (2) the mean size of the carcinoma was smaller in ACs (2.5 vs 3.2 cm; p < 0.001): when matched for invasion size, the survival advantage of AC was minimized, and when matched for invasion size larger than 2 cm, the survival advantage of AC lost its statistical significance; (3) lymph node (LN) metastases were less common in ACs (49 % vs 71 %; p < 0.001); (4) the definitive R1 rate was lower in ACs (4 % vs 23.5 %; p < 0.001); and (5) non-PB and non-tubular adenocarcinoma types were more common in ACs (17 % vs 3 %; p < 0.001)., Conclusions: Comparatively, ACs have better clinical survival than PCs. Potential contributing factors are the relative abundance of the preinvasive component, smaller invasion, lower LN metastasis rate, higher resectability, and common occurrence of less aggressive histologic phenotypes (intestinal, medullary, mucinous). However, this survival advantage is sustained even in PB-type ACs, highlighting the importance of accurately determining the site of origin., (© 2024. Society of Surgical Oncology.)

Background: A bridge to surgery (BTS) after self-expandable metallic stent (SEMS) placement is a widely recognized treatment strategy for obstructive colorectal cancer. However, there is still a lack of evidence for the efficacy and safety of laparoscopic surgery following SEMS placement. The aim of this systematic review and meta-analysis was to compare the short-term and long-term outcomes of laparoscopic surgery with those of open surgery following SEMS placement in patients with obstructive colorectal cancer., Methods: An electronic literature search through to December 2022 was performed to identify studies comparing short-term and long-term outcomes between laparoscopic and open surgery following SEMS placement for obstructive colorectal cancer. The main outcome measures were postoperative complication rates and mortality. Secondary outcome measures were the 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) rates. The meta-analysis was performed using fixed-effect or random-effects methods to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs)., Results: The meta-analysis included 15 studies and 883 patients, of whom 467 (52.9%) underwent laparoscopic surgery and 416 (47.1%) underwent open surgery following SEMS placement. The postoperative complication rate was significantly lower in the laparoscopic surgery group than in the open surgery group (OR 0.47, 95% CI 0.32-0.67, P < 0.001). There was no significant difference in the 3-year RFS rate or 3-year OS rate between the laparoscopic and open surgery groups (3-year RFS, OR 0.78, 95% CI 0.50-1.24, P = 0.30; 3-year OS, OR 0.68, 95% CI 0.41-1.12, P = 0.13)., Conclusion: This meta-analysis found that the short-term outcome was better in patients who underwent laparoscopic surgery following SEMS placement than in those who underwent open surgery. Furthermore, there was no significant difference in long-term outcomes between the two groups. Laparoscopic surgery following SEMS placement may be a safe and effective treatment option for obstructive colorectal cancer., (© 2024. The Author(s).)

Fidelity assessments can contribute to maintaining the adherence to the individual placement and support (IPS) model, which enhances vocational outcomes for individuals with mental illness worldwide. While independent reviews are standard, self-assessments could broaden the implementation of IPS. This study aimed to evaluate reviewer-rated and self-rated fidelity assessments using the Japanese version of the Individualized Supported Employment Fidelity Scale (JiSEF), and to compare the two assessment methods in terms of their correlations with employment outcomes in Japan. Over the 3-year research period, fidelity assessments were conducted by independent reviewers and trained program staff members across 26 programs, totaling 58 assessments. Analyses involved kappa statistics for item-level comparison, the intra-class correlation coefficient (ICC) and paired t-test for the overall fidelity scores, and Pearson's correlations to examine the relationship between the fidelity scores and program-level employment outcomes. Most individual JiSEF items demonstrated fair to good reliability between reviewer-rated and self-rated assessments. The ICC for the overall JiSEF scores between the two assessment methods was 0.756, yet the distribution of self-rated scores was more scattered compared with that of reviewer-rated scores. The mean total scores from self-assessments were significantly lower than those from reviewer assessments (t = 2.072, P = 0.043). While both sets of scores correlated significantly with employment rates (r = 0.640, P < 0.001 for reviewer assessments; r = 0.325, P = 0.013 for self-assessments), the correlation was stronger for reviewer ratings (z = 2.207, P = 0.027). Self-rated fidelity assessments offer several benefits. However, since independent reviews had a more normal distribution and higher correlation with employment outcome, they should remain the priority in fidelity assessments within the Japanese IPS framework., (© 2024. The Author(s).)

Background: Proper traction allows safer and easier endoscopic submucosal dissection; however, single-point traction may not be sufficient. In this study we assessed the safety, efficacy, and feasibility of our newly developed multipoint traction device., Methods: During an ex vivo study using a Konjac training model, two experts and two trainees resected 80 mock lesions of 20-mm diameter by performing endoscopic submucosal dissection with and without multipoint traction. The primary outcome was the success rate of the procedure involving traction. The secondary outcomes were the submucosal dissection time, dissection speed, and perforation during endoscopic submucosal dissection. During the in vivo study, to clarify the initial clinical outcomes, we used data from the electronic medical record of patients at our institution who underwent gastric and colorectal endoscopic submucosal dissection, which was performed by experts with our newly developed multipoint traction device, from March to December 2022., Results: The ex vivo study indicated that all traction procedures were successful. Higher resection speeds were observed with endoscopic submucosal dissection with traction than without traction (P < 0.001). Perforations were not observed. During the first in vivo clinical study, traction was feasible during 20 gastric and colorectal endoscopic submucosal dissection procedures. No adverse events occurred., Conclusions: Our multitraction device can increase the submucosal dissection speed and simplify endoscopic submucosal dissection techniques, thus safely reducing technical challenges. The application of this device for endoscopic submucosal dissection could lead to safer and more efficient procedures. Clinical registration UMIN Clinical Trials Registry, Japan (registration number UMIN000053384)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to assess the imaging features and postoperative natural course of 18 F-fluorodeoxyglucose (FDG) uptake in the cervical muscles after neck dissection., Materials and Methods: This study included 83 patients who underwent preoperative and postoperative 18 F-FDG-PET/CT and were diagnosed with head and neck malignancy after neck dissection. Postoperative 18 F-FDG-PET/CT was performed within 5 years after neck dissection. Preoperative and postoperative FDG uptake of the trapezius, sternocleidomastoid, scalene, pectoralis major, and deltoid muscles was visually assessed. Increased postoperative uptake was visually defined as higher postoperative FDG uptake than the preoperative one in the corresponding muscle. The maximum standardized uptake value (SUVmax) was measured in cases with increased postoperative uptakes., Results: Increased postoperative uptakes were observed in 43 patients (52%). The trapezius (31/83, 37%), sternocleidomastoid (19/83, 23%), and scalene (12/83, 14%) muscles were involved, as opposed to the pectoralis major and deltoid muscles were not. Increased postoperative uptakes were observed on the dissected side in all 43 patients. Significant differences between SUVmax estimated from the mixed-effects model and postoperative months were observed in the trapezius muscle (Coefficient (β) = -0.038; 95% confidence interval (CI): [-0.047, -0.028]; p < 0.001) and sternocleidomastoid muscle (β =  -0.015; 95% CI: [-0.029, -0.001]; p = 0.046)., Conclusions: Increased postoperative uptakes in the cervical muscles were observed on the dissected side in approximately half of the patients after neck dissection. The SUVmax in the trapezius and sternocleidomastoid muscles decreased after surgery over time., (© 2024. The Author(s).)

Introduction: The right intersectional plane and the right hepatic hilum were noted too often exhibit anatomical variations, making difficult the laparoscopic right anterior sectionectomy (LRAS)., Methods: We analyzed the anatomical features employing 3D-CT images of 55 patients, and evaluated these features according to the course of ventral branches of segment VI of the portal vein (PV, P6a) relative to the right hepatic vein (RHV)., Results: P6a run on the dorsal side of RHV in 32 patients (58%, Dorsal-P6a) and the ventral side of RHV in 23 (42%, Ventral-P6a). Ventral-P6a had more patients with S6 partially drained by middle hepatic vein (MHV, 39% vs. 0%, P < 0001), the narrower angle between the anterior and posterior branches of PV (73.1° vs. 93.8°, P = 0.006), the wider angle between the RHV and inferior vena cava  (54.3° vs. 44.3°, P < 0.001), and more steeply pitched angle between S6 and S7 along the RHV (140.6° vs. 162.0°, P < 0.001) compared to Dorsal-P6a., Conclusion: In LRAS for Dorsal-P6a patients, the transection surface was relatively flat. In LRAS for Ventral-P6a patients, the narrow space between anterior and posterior glissons makes difficult the glissonean approach. The transection plane was steeply pitched, and RHV was partially exposed. S6 was often partially drained to MHV in 39% of the Ventral-P6a patients, which triggers congestion during liver transection of a right intersectional plane after first splitting the confluence of this branch., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pancreatic fistula (PF) is one of the most serious postoperative complications of gastrectomy. Misidentification of the boundary between the pancreas and the dissected fat is a primary concern. In this study, we focused on differences in the appearance of the pancreas and the dissected fat in actual surgical images and statistically analyzed the relationship between the pancreas and the dissected fat., Methods: We analyzed data from 109 gastric cancer patients who underwent curative gastrectomy between November 2018 and March 2023. Intraoperative images were taken from videos of lymph node dissections of Nos.6 and 8a regions, and the mean gray value of the areas was measured using ImageJ software for analysis. The visceral fat area (VFA) was evaluated by preoperative axial CT at the umbilical level using Ziostation software., Results: A significant correlation was observed between the fat/pancreas gray value ratio in the No.8a lymph node region and the drain/serum amylase ratio (P < 0.001). The fat/pancreas gray value ratio in the No.6 lymph node region correlated with VFA (P < 0.001). The VFA and drain/serum amylase ratio were significantly higher in the group with intra-abdominal complications (P = 0.004)., Conclusions: We revealed significant relationships between the fat/pancreas gray value ratio with drain/serum amylase and VFA. Detecting differences in gray values between the pancreas and the dissected fat may lead to a decrease in the drain/serum amylase ratio and PF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility., Methods: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model., Results: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival., Conclusion: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients., (© 2024. Society of Surgical Oncology.)

Objectives: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy., Method: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy., Result: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases., Methods: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension., Results: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique., Conclusions: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Radiofrequency ablation (RFA) is a widely accepted, minimally invasive treatment modality for patients with hepatocellular carcinoma (HCC). Accurate prognosis prediction is important to identify patients at high risk for cancer progression/recurrence after RFA. Recently, state-of-the-art transformer models showing improved performance over existing deep learning-based models have been developed in several fields. This study was aimed at developing and validating a transformer model to predict the overall survival in HCC patients with treated by RFA., Methods: We enrolled a total of 1778 treatment-naïve HCC patients treated by RFA as the first-line treatment. We developed a transformer-based machine learning model to predict the overall survival in the HCC patients treated by RFA and compared its predictive performance with that of a deep learning-based model. Model performance was evaluated by determining the Harrel's c-index and validated externally by the split-sample method., Results: The Harrel's c-index of the transformer-based model was 0.69, indicating its better discrimination performance than that of the deep learning model (Harrel's c-index, 0.60) in the external validation cohort. The transformer model showed a high discriminative ability for stratifying the external validation cohort into two or three different risk groups (p < 0.001 for both risk groupings). The model also enabled output of a personalized cumulative recurrence prediction curve for each patient., Conclusions: We developed a novel transformer model for personalized prediction of the overall survival in HCC patients after RFA treatment. The current model may offer a personalized survival prediction schema for patients with HCC undergoing RFA treatment., (© 2023. The Author(s).)

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The diagnostic accuracy of exercise stress echocardiography (ESE) for myocardial ischemia requires improvement, given that it currently depends on the physicians' experience and image quality. To address this issue, we aimed to develop artificial intelligence (AI)-based slow-motion echocardiography using inter-image interpolation. The clinical usefulness of this method was evaluated for detecting regional wall-motion abnormalities (RWMAs). In this study, an AI-based echocardiographic image-interpolation pipeline was developed using optical flow calculation and prediction for in-between images. The accuracy for detecting RWMAs and image readability among 25 patients with RWMA and 25 healthy volunteers was compared between four cardiologists using slow-motion and conventional ESE. Slow-motion echocardiography was successfully developed for arbitrary time-steps (e.g., 0.125×, and 0.5×) using 1,334 videos. The RWMA detection accuracy showed a numerical improvement, but it was not statistically significant (87.5% in slow-motion echocardiography vs. 81.0% in conventional ESE; odds ratio: 1.43 [95% CI: 0.78-2.62], p = 0.25). Interreader agreement analysis (Fleiss's Kappa) for detecting RWMAs among the four cardiologists were 0.66 (95%CI: 0.55-0.77) for slow-motion ESE and 0.53 (95%CI: 0.42-0.65) for conventional ESE. Additionally, subjective evaluations of image readability using a four-point scale showed a significant improvement for slow-motion echocardiography (2.11 ± 0.73 vs. 1.70 ± 0.78, p < 0.001).In conclusion, we successfully developed slow-motion echocardiography using in-between echocardiographic image interpolation. Although the accuracy for detecting RWMAs did not show a significant improvement with this method, we observed enhanced image readability and interreader agreement. This AI-based approach holds promise in supporting physicians' evaluations., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conducted single-cell expression profiling, and compared the gene expression with and without stimuli. We identified the cells and genes whose expression levels change directly in response to light stimuli. Among the genes altered by light stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under the light-stimulated condition. Consistently, the insulin-like growth factor (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor cell death, and its treatment in combination with the endothelin receptor antagonist led to the blockade of abnormal glial activation and the promotion of glycolysis, thereby resulting in the improvement of retinal functions, as assayed by electroretinography. We additionally demonstrated that the attenuation of mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, leads to complications in maintaining retinal homeostasis. Together, we propose that combinatorial manipulation of distinct mechanisms is useful for the maintenance of the retinal condition., (© 2024. The Author(s).)

Background: The potential of membrane transporters activated in cancer stem cells (CSCs) as new therapeutic targets for cancer is attracting increasing interest. Therefore, the present study examined the expression profiles of ion transport-related molecules in the CSCs of esophageal adenocarcinoma (EAC)., Methods: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from OE33 cells, a human Barrett's EAC cell line, by fluorescence-activated cell sorting. CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were examined by a microarray analysis., Results: Among OE33 cells, ALDH1A1 messenger RNA levels were higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels/transporters, such as transient receptor potential vanilloid 2 (TRPV2) and solute carrier family 12 member 2 (SLC12A2). The cytotoxicities of the TRPV2 inhibitor tranilast and the SLC12A2 inhibitor furosemide were higher at lower concentrations in CSCs than in non-CSCs, and both markedly reduced the number of tumorspheres. The cell population among OE33 cells that highly expressed ALDH1A1 also was significantly decreased by these inhibitors., Conclusions: Based on the present results, TRPV2 and SLC12A2 are involved in the maintenance of CSCs, and their specific inhibitors, tranilast and furosemide, respectively, have potential as targeted therapeutic agents for EAC., (© 2023. Society of Surgical Oncology.)

Background: Transient receptor potential vanilloid 2 (TRPV2) is a member of the TRP superfamily of non-specific cation channels with functionally diverse roles. We herein investigated the effects of TRPV2 on the expression of programmed cell death-ligand 1 (PD-L1) and its binding ability to programmed cell death-1 (PD-1) in gastric cancer (GC)., Methods: Knockdown (KD) experiments were performed on human GC cell lines using TRPV2 small-interfering RNA. The surface expression of PD-L1 and its binding ability to PD-1 were analyzed by flow cytometry. Eighty primary tissue samples were assessed by immunohistochemistry (IHC), and the relationships between IHC results, clinicopathological factors, and patient prognosis were analyzed. The molecular mechanisms underlying the effects of TRPV2 on the intracellular ion environment were also investigated., Results: TRPV2-KD decreased the expression level of PD-L1 in NUGC4 and MKN7 cells, thereby inhibiting its binding to PD-1. A survival analysis revealed that 5-year overall survival rates were significantly lower in the TRPV2 high expression and PD-L1-positive groups. In IHC multivariate analysis of GC patients, high TRPV2 expression was identified as an independent prognostic factor. Furthermore, a positive correlation was observed between the expression of TRPV2 and PD-L1. An immunofluorescence analysis showed that TRPV2-KD decreased the intracellular concentration of calcium ([Ca 2+ ] i ). Treatment with ionomycin/PMA (phorbol 12-myristate 13-acetate), which increased [Ca 2+ ] i , upregulated the protein expression of PD-L1 and promoted its binding to PD-1., Conclusions: The surface expression of PD-L1 and its binding ability to PD-1 in GC were regulated by TRPV2 through [Ca 2+ ] i , indicating the potential of TRPV2 as a biomarker and target of immune checkpoint blockage for GC., (© 2023. Society of Surgical Oncology.)

Purpose: We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort., Patients and Methods: From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer., Results: A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis., Conclusions: We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy., (© 2023. Society of Surgical Oncology.)

Purpose: The gut microbiome plays an important role in cancer pathogenesis and therapy. Some studies have reported that specific bacteria in tumor tissues may contribute to the prognosis and treatment of esophageal squamous cell carcinoma (ESCC). However, there is limited evidence that the gut microbiome is associated with ESCC. This study assessed the utility of the gut microbiome as a predictive marker of the therapeutic effect in patients with ESCC undergoing chemo-radiotherapy (CRT)., Patients and Methods: Fecal samples were collected from 51 patients with ESCC who had never undergone treatment between April 2021 and May 2022 in the Department of Frontier Surgery, Chiba University. The gut microbiome was analyzed using 16S metagenomics sequencing. The association between the gut microbiome composition and stage according to the TNM classification (American Joint Committee on Cancer 7.0) and CRT response according to the RECIST criteria was evaluated., Results: The relative abundance of Fusobacteriaceae was enriched in cStage III-IVb group. Among the 27 patients who received CRT, the relative abundance of Lactobacillaceae was enriched in those with a partial and complete response. Lactobacillaceae also did not correlate with any clinical data, but the high Lactobacillales group had a higher LMR (P = 0.032) and lower PLR (P = 0.045) than in the low Lactobacillales group., Conclusions: In conclusion, we found that the relative abundance of Lactobacillaceae was enriched in patients with a partial or complete response among CRT those with ESCC, thus suggesting that the relative abundance of Lactobacillaceae can predict the effect of CRT., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

In traditional Japanese medicine, Rhei Rhizoma is used as a purgative, blood stasis-resolving and antipsychotic drug. The latter two properties are possibly related to anti-inflammatory effects. Microglia regulate inflammation in the central nervous system. M1 microglia induce inflammation, while M2 microglia inhibit inflammation and show neurotrophic effects. This study investigated the effects from water extracts of roots of cultivated Rheum species in Nagano Prefecture, Japan (strain C, a related strain to a Japanese cultivar, 'Shinshu-Daio'; and strain 29, a Chinese strain) and 3 kinds of Rhei Rhizoma available in the Japanese market, and also examined their constituents on the polarization of cultured microglia. All extracts significantly decreased M1 microglia, and strains C and 29 significantly increased M2 microglia. Furthermore, the extracts of both strains significantly increased the M2/M1 ratio. Among the constituents of Rhei Rhizoma, ( +)-catechin (2), resveratrol 4'-O-β-D-(6″-O-galloyl) glucopyranoside (5), isolindleyin (8), and physcion (15) significantly increased the M2/M1 ratio. The contents of the constituents in water extract of each strain were quantified using HPLC. The extracts of strains C and 29 contained relatively large amounts of 2 and 5; and 2, 8, and 15, respectively. This study showed the water extracts of roots of cultivated Rheum strains in Japan had the effects of M2 polarization of microglia, suggesting that these strains become the candidate to develop anti-inflammatory Rhei Rhizoma. Moreover, the suitable chemical composition to possess anti-inflammatory activity in the brain was clarified for the future development of new type of Rhei Rhizoma., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies., Methods: We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated., Results: Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases., Conclusion: Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy., (© 2023. Springer Science+Business Media, LLC.)

Background: Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, the transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, particularly around the aortic arch to the tracheal bifurcation, may increase the difficulty of this procedure. The present study aimed to clarify predictors of the difficulty of transcervical SCLN dissection., Methods: Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of mediastinal narrowness by 3D-CT. The relationships between the difficulty of transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated., Results: In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with difficulty. The median cervical angle and aorta distance were 15° and 33 mm in difficult cases and 19° and 43 mm in easy cases, respectively. In a multivariate analysis, the short aorta distance (odds ratio: 7.96, p = 0.002) and middle thoracic tumor (odds ratio: 3.35, p = 0.042) were independent predictive factors., Conclusions: The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, a transhiatal approach should be combined for complete SCLN dissection., (© 2023. The Author(s).)

The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) introduced a system for the certification of laparoscopic surgeons in 2002 and a system for the certification of facilities in 2014. We examined the opinions of the members of the Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) regarding the necessity of a certification training system and a technical certification system for robotic surgery skills in Japan. Members of the JSGOE were surveyed with two questionnaires. Overall, 870 and 519 participants responded to the first and second questionnaires, respectively. Half of the respondents indicated that both systems were necessary. The breakdown by age and qualifications showed that this was especially true for the younger generation and respondents with more experience with robotic surgery. Overall, 40% of the respondents judged that a certification system for robotic surgery alone (with or without certification in laparoscopic surgery but with a requirement of experience in laparoscopic surgery) would be necessary. The opinions of the JSGOE members on making a certification system for robotic surgery were split into two clear-cut camps. Thus, we must further seek the extent of public demand for using a public survey so that a final decision can be made on whether to establish this system., (© 2023. The Author(s).)

Herein, we report a novel strategy toward non-volatile optical memory with high-contrast, high-speed recording, and non-destructive readout capability based on the cooperative out-of-plane orientation of a fluorescent dye doped into azobenzene liquid crystalline polymer film. By employing the out-of-plane orientation switching upon irradiation with UV light and thermal heating, high-contrast turn-on fluorescence switching was successfully achieved and the optical recording was demonstrated with non-destructive fluorescence readout capability. Furthermore, the recording speed and the fluorescence on/off contrast in the present system were dramatically improved compared to the previous in-plane orientation mode., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Clinical outcomes concerning the efficacy of excimer laser coronary angioplasty (ELCA) in real-world cases of acute myocardial infarction (MI) are limited. We evaluated and compared the impact of ELCA with manual aspiration thrombectomy on myocardial salvage and left ventricular (LV) systolic/diastolic function in patients with ST-segment elevation MI (STEMI) using nuclear scintigraphy.  We enrolled 143 consecutive patients with STEMI treated with ELCA (63 patients) or manual aspiration thrombectomy (80 patients) between September 2016 and December 2020 in a single-center hospital. We evaluated the peak creatine kinase (CK)/ creatine kinase-myocardial band (CK-MB) levels and performed single-photon emission computed tomography (SPECT) analyses with Quantitative Gated SPECT and Quantitative Perfusion SPECT (Auto QUANT 7.2) at 3-10 days using 123 I-BMIPP and 3 months following percutaneous coronary intervention using 99m Tc-tetrofosmin to evaluate myocardial salvage and LV systolic/diastolic function. No significant difference was observed in the patient and periprocedural characteristics. Peak CK-MB level was significantly different between the groups (ELCA group, 190.0 [70.5-342.0] IU/L vs. aspiration group, 256.5 [157.0-354.8] IU/L, p = 0.047). Although no significant difference was observed in myocardial salvage, significant improvement in the LV ejection fraction (14.1 [6.2-19.8]% vs. 9.5 [3.9-15.3]%, respectively, p = 0.018) and peak emptying rate (-0.54 [-1.02- (-0.27)] mL/s vs. -0.38 [-0.76- (-0.05)] mL/s, respectively, p = 0.017) were detected. ELCA could suppress the myocardial deviation enzymes and potentially improve systolic function compared to manual aspiration thrombectomy in patients with STEMI., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

To show that quantification of abnormal respiratory sounds by our developed device is useful for predicting respiratory failure and airway problems after extubation. A respiratory sound monitoring system was used to collect respiratory sounds in patients undergoing extubation. The recorded respiratory sounds were subsequently analyzed. We defined the composite poor outcome as requiring any of following medical interventions within 48 h as defined below. This composite outcome includes reintubation, surgical airway management, insertion of airway devices, unscheduled use of noninvasive ventilation or high-flow nasal cannula, unscheduled use of inhaled medications, suctioning of sputum by bronchoscopy and unscheduled imaging studies. The quantitative values (QV) for each abnormal respiratory sound and inspiratory sound volume were compared between composite outcome groups and non-outcome groups. Fifty-seven patients were included in this study. The composite outcome occurred in 18 patients. For neck sounds, the QVs of stridor and rhonchi were significantly higher in the outcome group vs the non-outcome group. For anterior thoracic sounds, the QVs of wheezes, rhonchi, and coarse crackles were significantly higher in the outcome group vs the non-outcome group. For bilateral lateral thoracic sounds, the QV of fine crackles was significantly higher in the outcome group vs the non-outcome group. Cervical inspiratory sounds volume (average of five breaths) immediately after extubation was significantly louder in the outcome group vs non-outcome group (63.3 dB vs 54.3 dB, respectively; p < 0.001). Quantification of abnormal respiratory sounds and respiratory volume may predict respiratory failure and airway problems after extubation., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant cancer with a poor prognosis. Chemoradiotherapy is one of the most important strategies for patients with locally advanced unresectable ESCC; however, its therapeutic effect is unsatisfactory. Tumor-initiating cells (TICs) have been reported to be resistant to conventional chemotherapy and radiotherapy so far. Therefore, we aimed to develop a treatment strategy targeting TICs in ESCC to improve radiosensitivity., Methods: First, we validated aldehyde dehydrogenase 1 (ALDH1) as a TIC marker and investigated its ability to mediate resistance in human ESCC cell lines using flow cytometry, Western blotting, and functional analyses. Then, we focused on disulfiram (DSF), an aldehyde dehydrogenase inhibitor, used to treat alcohol use disorder. We investigated the effect of DSF and copper (II) D-gluconate (Cu) on the radiosensitivity of ESCC in xenograft mouse models., Results: ALDH1-positive cells showed an upregulation of SOX2 and Nanog, exhibiting much stronger tumor-initiating properties than ALDH1-negative cells. Furthermore, inhibition of ALDH1 attenuated the tumor-initiating properties of ESCC cell lines. Our results also showed that ALDH1-positive cells were resistant to chemotherapy and radiotherapy, and the inhibition of ALDH1 led to the mitigation of therapeutic resistance. Our in vitro and in vivo studies revealed that the DSF/Cu complex could radiosensitize ALDH1-positive ESCC cells and downregulate the phosphoinositide 3-kinase/Akt pathway., Conclusion: ALDH1 inhibition by the DSF/Cu complex enhances the radiosensitivity of TICs in ESCC. The drug repositioning approach using disulfiram is a potential treatment option to overcome radioresistance in patients with locally advanced ESCC., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Assessment of respiratory sounds by auscultation with a conventional stethoscope is subjective. We developed a continuous monitoring and visualization system that enables objectively and quantitatively visualizing respiratory sounds. We herein present two cases in which the system showed regional differences in the respiratory sounds. We applied our novel continuous monitoring and visualization system to evaluate respiratory abnormalities in patients with acute chest disorders. Respiratory sounds were continuously recorded to assess regional changes in respiratory sound volumes. Because we used this system as a pilot study, the results were not shown in real time and were retrospectively analyzed. Case 1 An 89-year-old woman was admitted to our hospital for sudden-onset respiratory distress and hypoxia. Chest X-rays revealed left pneumothorax; thus, we drained the thorax. After confirming that the pneumothorax had improved, we attached the continuous monitoring and visualization system. Chest X-rays taken the next day showed exacerbation of the pneumothorax. Visual and quantitative findings showed a decreased respiratory volume in the left lung after 3 h. Case 2 A 94-year-old woman was admitted to our hospital for dyspnea. Chest X-rays showed a large amount of pleural effusion on the right side. The continuous monitoring and visualization system visually and quantitatively revealed a decreased respiratory volume in the lower right lung field compared with that in the lower left lung field. Our newly developed continuous monitoring and visualization system enabled quantitatively and visually detecting regional differences in respiratory sounds in patients with pneumothorax and pleural effusion., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

We assessed whether the severity of anastomotic urinary leakage detected during routine cystourethrography after robot-assisted laparoscopic prostatectomy (RALP) affects urinary continence recovery. Around 302 patients who underwent RALP between August 2013 and May 2019 were included retrospectively. According to routine cystourethrographic findings obtained on the sixth or eighth postoperative day, which indicated leakage severity, patients were divided into three groups: no-leakage, grade 1 (linear shaped leakage, but not spreading), and grade 2 (spreading strip-shaped leakage). The preoperative factors and intraoperative factors were compared between no-leakage and leakage group (grade 1 and grade 2). Continence recovery was compared between the three groups. Continence recovery was defined as no pad used or one security pad used in a day. Cystourethrography revealed anastomotic urinary leakage in 44 patients (14.5%), of which 20 patients (6.6%) had grade 1 leakage and 24 patients (7.9%) had grade 2 leakage. On multivariate logistic regression analysis, the only significant predictor for urethrovesical anastomotic urinary leakage on cystourethrography following RALP was intraoperative anastomotic leakage (OR 5.306; 95% CI 1.530-18.398, p = 0.009). Continence recovery rates for no-leakage, grade 1 leakage, and grade 2 leakage groups were 11%, 20%, and 25% after 1 month (P = 0.131); 25%, 25%, and 45.8% after 3 months (P = 0.474); 44.6%, 55%, and 60.8% after 6 months (P = 0.184); and 63.1%, 87.5%, and 78.2% after 12 months (P = 0.095), respectively. In conclusion, urinary leakage in urethrovesical anastomosis, even at its severity, had no negative effects on continence recovery after RALP., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background and Aims: New image-enhanced endoscopy (IEE), blue Light Imaging (LED-BLI) is launched in USA and Europe, whereas Blue Laser Imaging (Laser-BLI) is available only Asian and some countries. No studies have directly compared the diagnostic accuracy of narrow band imaging (NBI), Laser-BLI and LED-BLI for colorectal tumors. The present study aimed to compare the diagnostic accuracy of the three methods for colorectal tumor using the NBI international colorectal endoscopic (NICE) classification and the Japanese NBI Expert Team (JNET) classifications., Methods: This was a multi-center evaluator-blinded, randomized control trial of patients who underwent endoscopic colorectal tumor resection. The patients were randomly assigned to NBI, Laser-BLI or LED-BLI. Cropped images were sent to blinded external evaluators and diagnosed according to NICE and JNET classifications. The diagnostic accuracy of each endoscopy system was compared with non-inferiority test., Results: A total of 619 colonic tumors were resected from 230 patients and evaluated by external four evaluators. The diagnostic accuracy of NBI for NICE 1, NICE 2, NICE 3 was 90.6%, 90.3% and 99.5%, respectively and for JNET 1, JNET 2A, JNET 2B and JNET 3, it was 94.6%, 72.0%, 79.2% and 99.1%, respectively. In non-inferiority test, Laser-BLI and LED-BLI revealed non-inferiority to NBI in all NICE and JNET categories (p&lt;0.001)., Conclusions: Laser-BLI and LED-BLI had high diagnostic accuracy and non-inferiority of NBI, especially for hyperplastic polyp/sessile serrated lesion and low-grade dysplasia. This is first trial to compare the diagnostic accuracy with NBI, Laser-BLI and LED-BLI and useful to understand the position of each IEE. This trial was registered as UMIN000032107., (© 2022. The Author(s).)

Purpose: To compare the diagnostic performance for detecting vascular involvement and determining resectability differences regarding pancreatic ductal adenocarcinoma (PDAC) between contrast-enhanced CT and MRI., Methods: This retrospective study evaluated 82 patients (73 years, 46 men) with PDAC who underwent both preoperative contrast-enhanced CT and MRI from January 2008 to March 2021. Two radiologists independently categorized vascular involvements for celiac, superior mesenteric, splenic, and common hepatic arteries, and portal, superior mesenteric, and splenic veins into no tumor contact, solid soft-tissue contact ≤ 180°, or solid soft-tissue contact > 180°. The radiologists also classified resectability into resectable, borderline resectable, or locally advanced. Receiver-operating-characteristic (ROC) analysis was conducted to evaluate the diagnostic performances for detecting vascular involvements which were confirmed by pathological or intraoperative findings. The proportion of resectability classifications was compared between CT and MRI by the Fisher's exact test., Results: No statistical difference was found in the diagnostic performances for detecting vascular involvement in CT (area under the ROC curve [AUC], 0.50-0.89) and MRI (AUC, 0.51-0.75) (P = 0.06-> 0.99). Resectability on CT were 79% and 68%, 20% and 26%, and 1% and 6% for resectable, borderline resectable, and locally advanced tumors for reviewers 1 and 2; those on MRI were 87% and 81%, 12% and 13%, and 1% and 6%, respectively. The proportion of resectability classifications was not different between CT and MRI (P = 0.48 and = 0.15 for reviewers 1 and 2, respectively)., Conclusion: The diagnostic performance for detecting vascular involvement and determining resectability of PDAC on contrast-enhanced MRI were comparable with pancreatic protocol CT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: While an association between esophago-gastric junctional adenocarcinomas (EGJACs) and obesity, especially visceral obesity, has been suggested in Western countries, the association remains unclear in Asia, including Japan. In this population-based case-control study, we investigated the association between EGJACs and obesity., Methods: To perform near-population-based data collection for all early-stage EGJACs occurring in Akita Prefecture from 2014 to 2019, clinical data, including endoscopic and computed tomography (CT) findings, were collected from 11 cancer treatment base hospitals in the area. Age- and gender-matched controls were extracted at a case-to-control ratio of 1:2 from healthy subjects who received health checkups in the same area. The visceral fat area (VFA) was calculated using CT images. Logistic regression analyses were performed to investigate the associations between EGJACs and obesity-related parameters., Results: In total, 74 EGJAC cases (62 males, median age of 70 years old) and 148 controls were extracted. Multivariable analyses showed a significantly negative association between the BMI and EGJACs and a significantly positive association between the VFA and EGJACs with odds ratios (ORs) (95% confidence intervals [CIs]) of 0.65 (0.53-0.80) and 1.01 (1.01-1.02), respectively. These findings were confirmed in another dataset (40 EGJACs and 80 controls). In addition, as a categorical variable, VFA ≥ 100 cm 2 showed a significantly positive association with EGJACs (OR [95% CI] 1.96 [1.02-3.76])., Conclusions: We found paradoxical associations between EGJACs and obesity-related parameters (BMI vs. VFA) in a Japanese population, suggesting a potentially pivotal role of the VFA rather than the BMI as a risk factor for EGJACs., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects., (© 2022. Journal of NeuroVirology, Inc.)