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This study presents a novel approach to control "linked property changes" in hydrogels. Specifically, we controlled the swelling behaviour without altering the bulk elastic modulus by grafting polymers selectively into the surface region of the gels, while varying the graft amount.

Background: To improve the outcome in newly diagnosed glioblastoma patients with maximal resection, we aimed to evaluate the efficacy and safety of implantation of carmustine wafers (CWs), radiation concomitant with temozolomide and bevacizumab, and maintenance chemotherapy with six cycles of temozolomide and bevacizumab., Method: This prospective phase II study enrolled glioblastoma patients considered candidates for complete resection (> 90%) of a contrast-enhanced lesion. The CWs were intraoperatively implanted into the resection cavity after achieving maximal resection. Patients without a measurable contrast-enhanced lesion on magnetic resonance imaging within 48 h after resection received concomitant radiotherapy and chemotherapy with temozolomide and bevacizumab, followed by maintenance treatment with up to six cycles of temozolomide and bevacizumab. The primary endpoint was the 2-year overall survival rate in glioblastoma patients with protocol treatment., Results: From October 2015 to April 2018, we obtained consent for the first registration from 70 patients across 17 institutions in Japan, and 49 patients were treated according to the protocol. We evaluated the safety in 49 patients who were part of the second registration and the efficacy in 45 glioblastoma patients treated according to the protocol. The profile of hematological and most of the non-hematological adverse effects was similar to that in previous studies, but stroke occurred in 12% of cases (6/49 patients). The estimated 2-year overall survival rate was 51.3%., Conclusion: Implantation of CWs, followed by concomitant radiation, temozolomide, and bevacizumab, and six cycles of temozolomide and bevacizumab may offer some benefit to survival in Japanese glioblastoma patients with maximal resection., Trial Id: jRCTs021180007., Competing Interests: Declarations. Conflict of interest: Masayuki Kanamori received a grant from Eisai Co. Ltd., and lecture honoraria from Eisai Co. Ltd. and Novocure Co. Ltd. Ichiyo Shibahara received lecture honoraria from Eisai Co. Ltd. and Novocure Co. Ltd. Yoshiteru Shimoda received a grant from Eisai Co. Ltd. Shigeo Ohba received lecture honoraria from Eisai Co. Ltd., and Novocure Co. Ltd. Toshiyuki Enomoto received lecture honoraria from Eisai Co. Ltd. and Novocure Co. Ltd. Mitsuto Hanihara received lecture honoraria from Eisai Co. Ltd. Yohei Mineharu received lecture honoraria from Eisai Co. Ltd., and Novocure Co. Ltd. Joji Ishida received lecture honoraria from Eisai Co. Ltd. Kenichiro Asano received lecture honoraria from Eisai Co. Ltd. Yasuyuki Yoshida received lecture honoraria from Eisai Co. Ltd. Manabu Natsumeda received lecture honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., and Novocure Co. Ltd., and support for travel for the conference from Eisai Co. Ltd., and Novocure Co. Ltd. Tatsuya Abe received grant from Chugai Pharmaceutical Co., Ltd. and lecture honoraria from Chugai Pharmaceutical Co., Ltd. and Novocure Co. Ltd. Hajime Yonezawa received lecture honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., and Novocure Co. Ltd. Soichiro Shibui received lecture honoraria from Chugai Pharmaceutical Co., Ltd. Ryuta Saito received lecture honoraria from Eisai Co. Ltd. and Novocure Co. Ltd. Yoshiki Arakawa received grant from Chugai Pharmaceutical Co., Ltd. and Eisai Co. Ltd. and lecture honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., Nippon Kayaku. and Novocure Co. Ltd. Yukihiko Sonoda received lecture honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., and Novocure Co. Ltd. Yuichi Hirose received a grant from Eisai Co. Ltd. and honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., and Novocure Co. Ltd. Toshihiro Kumabe received lecture honoraria and travel support from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., and Novocure Co. Ltd. Hidenori Endo received a grant from Eisai Co. Ltd. Teiji Tominaga received a grant from Eisai Co. Ltd. and honoraria from Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., Nippon Kayaku, MSD, and Novocure Co. Ltd. Yukinori Akiyama, Takaaki Beppu, Yuta Mitobe, Takahiro Ono, Sadahiro Nomura, Ryuichi Katakura, Toshihiko Kuroiwa, Hiroyoshi Suzuki, Hidehiro Takei, and Haruo Matsushita have no conflict of interest. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki and the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects. The Institutional Review Board of Tohoku University provided approval for the study (CRB2200003). The Institutional Review Board of Tohoku University Hospital provided approval for the molecular analysis (2015-2-126–1, 2023-1-971). Informed consent statement: Informed consent was obtained from all subjects involved in the study., (© 2024. The Author(s).)

An increase in cervical cancer incidence has been reported in Japan. The Ministry of Health, Labor, and Welfare of Japan has resumed the active recommendation of regular HPV vaccines in 2022. In Japan, the preventive effect of CIN3+ in the real world has not yet been demonstrated in age-adjusted cohort or case-control studies. This study aimed to estimate the effect of the HPV vaccine against CIN3+ in Japanese women. This nationwide case-control study from April 2013 to March 2020 targeted women aged 20-26 years old at the time of cervical screening. We compared HPV vaccination exposure between those with abnormal and those with normal cytology. Abnormal cytology was classified into cervical intraepithelial neoplasia (CIN)1+, CIN2+, and CIN3+. We calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 -OR) × 100. A total of 2790 cases and 13,990 controls (one-to-five matching) were eligible in 37 municipalities in Japan. In this study, 61 CIN3 (2.2%) and 10 squamous cell carcinomas (SCC) (0.4%) were found. The OR for CIN3+ versus controls was 0.14 (95% CI, 0.03-0.75), equating to a vaccine effectiveness of 86%. Of the 10 patients who had SCC none were vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in CIN3+ among women who did versus those who did not receive HPV vaccination., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: Neoadjuvant chemoradiotherapy (nCRT) is employed for the local control of locally advanced rectal cancer; however, its prognostic impact is limited and often impairs pelvic organ function. Therefore, careful patient selection is essential. This study aimed to investigate the impact of nCRT on relapse-free survival (RFS) by stratifying patients according to MRI detected circumferential resection margin (mrCRM) or extramural vascular invasion (mrEMVI), as the ability of MRI findings to identify patients who will have beneficial outcomes from nCRT is uncertain., Methods: We retrospectively analyzed patients with clinical stage II-III lower rectal cancer who underwent surgical resection with or without nCRT between 2010 and 2011 at 69 hospitals in Japan. The impact of nCRT on RFS was evaluated using multivariable Cox regression models in the entire cohort and in subgroups stratified by mrCRM or mrEMVI status., Results: In the entire cohort (nCRT, n = 172; surgery alone, n = 503), nCRT showed a trend toward improved RFS, although the difference was not statistically significant (HR, 0.74; 95 % CI, 0.54-1.03; P = 0.074). Among mrCRM-negative and mrEMVI-negative patients, there were no significant differences in RFS between the nCRT and surgery-alone groups. Among mrCRM-positive patients, nCRT tended to improve the RFS (HR, 0.70; 95 % CI, 0.46-1.06; P = 0.089). Among mrEMVI-positive patients, nCRT significantly prolonged the RFS (HR, 0.62; 95 % CI, 0.38-1.00; P = 0.048)., Conclusions: Compared to surgery alone, nCRT did not significantly improve RFS in the overall population but significantly improved RFS in mrEMVI-positive patients., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Detection of microorganisms from bovine using real-time PCR (Dembo PCR) is a comprehensive detection technique that was developed to detect pathogens causing bovine diseases. In Japan, the definitive tests for monitored infectious diseases, which are defined by law, are carried out at government agencies. On the other hand, the existence of pathogens other than monitored infectious diseases are not well understood. From the perspective of livestock quarantine, it is important to make it possible to identify pathogens other than monitored infectious diseases, so we extended the existing Dembo PCR system in this study. In particular, the number of targets other than monitored infectious disease was increased. The new version of Dembo PCR may be useful in elucidating new pathologies associated with multiple pathogens.

Developing artificial autonomous materials is crucial for a deeper understanding of the emergence of life-like behavior. In nature, cells achieve autonomy through chemical processing systems incorporated into soft material-based frameworks. Inspired by natural cells, we herein describe a straightforward methodology for constructing artificial autonomous materials consisting of a polymer-based chemical processing system and a hydrogel-based soft framework. Using a material comprising a hydrogel framework devoid of active components in combination with semi-interpenetrating self-oscillating linear polymers, we discovered that semi-interpenetrating polymer-based chemical processing systems drive the autonomous motion of the hydrogel framework. The material exhibited autonomous volumetric oscillation powered by the Belousov-Zhabotinsky reaction. Furthermore, the autonomous behavior is controllable by changing the content of the chemical processing system incorporated into the hydrogel framework. Our findings shed light on a class of autonomous materials based on polymer-based chemical processing systems with soft frameworks.

Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for diabetes patients. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55,000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions. K-3 preferentially acts on stage 3 pancreatic progenitor cells and increases the population expressing high levels of PDX1. As a result, the ratios of the PSC-derived PDX1 / NKX6.1 double-positive endocrine progenitor and INS / NKX6.1 double-positive mono-hormonal endocrine cells were increased. K-3 enhances the expression of functional pancreatic β cell markers and affects biological processes concerning organ development. K-3 also increased the yield of endocrine cells at the end of stage 5. The novel compound is a beneficial new tool for efficiently generating PSC-derived insulin-producing cells with high functionality and differentiation efficiency., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Wilms' tumor protein 1 (WT1)-targeted immunotherapy has been used in patients with leukemia and solid tumors. However, the spontaneous WT1-specific immune response before WT1 peptide vaccination in patients with WT1-expressing tumors (PTs) remains unclear. Therefore, we investigated whether WT1-specific cytotoxic CD8 + T-lymphocytes (CTLs) are clonally expanded in the peripheral blood outside of tumor sites. Clonal expansion of WT1 126 peptide (a.a.126-134)-specific CTLs (WT1 126 -CTLs) was compared between seven PTs and five healthy volunteers (HVs), and their T-cell receptors (TCRs) were analyzed at the single-cell level. Overall, 433 and 351 TCR β-chains of WT1 126 -CTLs were detected from PTs and HVs, respectively, and complementarity-determining region 3 was sequenced for clonality analysis. The frequencies of WT1 126 -CTLs were higher in human leukocyte antigen (HLA)-A*02:01 + PTs than in HLA-A*02:01 + HVs, although the difference was not statistically significant. WT1 126 -CTLs of differentiated types, including memory and effector, were higher in PTs than in HVs; whereas, those of the naïve type were higher in HVs than in PTs. WT1 126 -CTL clonality was significantly higher in PTs than in HVs. Furthermore, the frequency of effector WT1 126 -CTLs positively correlated with WT1 126 -CTL clonality in PTs; whereas, the frequency of naïve phenotype WT1 126 -CTLs tended to be negatively correlated with clonality. In conclusion, these results suggest that the WT1 protein in tumor cells is highly immunogenic, thereby stimulating endogenous naïve-type WT1 126 -CTLs and enabling them to clonally expand and differentiate into effector-type WT1 126 -CTLs., (© 2024. The Author(s).)

Background: Considerable interobserver variability exists in diagnosis of ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to histopathological similarities. While homologous recombination deficiency (HRD) correlates with drug sensitivity in HGSC, the molecular features of HGEC are unclear., Methods: Fresh-frozen samples from 15 ovarian HGECs and 274 ovarian HGSCs in the JGOG-TR2 cohort were submitted to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array. We additionally analyzed 555 ovarian HGSCs from TCGA-OV and 287 endometrial high-grade carcinomas from TCGA-UCEC., Results: Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4). C1 (n = 41) showed CCNE1 amplification and poor survival. C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively. C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Notably, C4 exhibited a normal endometrium-like DNA methylation profile, thus, defined as "HGEC-type" tumors, which were also identified in TCGA-OV and TCGA-UCEC., Conclusions: Ovarian "HGEC-type" tumors present a non-HRD status, favorable prognosis, and endometrial differentiation, possibly constituting a subset of clinically diagnosed HGSCs., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: This study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery., Methods: Yielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks., Results: The peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months., Discussion: The incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Efficacy of tumor embolization for posterior fossa meningioma is controversial due to the lack of adequate embolization for dangerous feeders. Of these, a meningohypophyseal trunk (MHT) has high therapeutic value despite the high risks associated with embolization., Materials and Methods: To analyze the utility of preoperative MHT embolization for posterior fossa meningiomas using n- BCA with dual balloon protection, a single center retrospective record review was performed on eight consecutive patients who underwent preoperative tumor embolization via the MHT for posterior fossa meningiomas between 2020 and 2024., Results: All patients successfully embolized the MHT using n- BCA. Complete obliteration was achieved in five cases, which is related to the tentorial artery alone as the feeding vessel. None of the patients had cerebral infarction associated with distal embolization. One patient experienced worsening of preoperatively observed abducens nerve palsy due to cranial nerve ischemia. Gross total resection was achieved in seven of eight cases. The mean estimated blood loss during surgical resection was 186 mL (range, 39-392 mL). The mean operative time was 431 min (range, 317-767 min)., Conclusions: The MHT embolization of posterior fossa meningiomas by using n- BCA is technically feasible with a high success rate and an acceptable complication rate., Abbreviations: MHT=meningohypophyseal trunk; ILT=inferolateral trunk; CPA=Cerebellopontine angle; BGC=balloon guide catheter; PVA=polyvinyl alcohol; GTR=Gross Total Resection; CN=Cranial nerve., (© 2024 by American Journal of Neuroradiology.)

Cancer stem cells are associated with aggressive phenotypes of malignant tumors. A prominent feature of uterine endometrial cancer is the activation of the PI3K-Akt-mTOR pathway. In this study, we present variations in sensitivities to a PI3K-Akt-mTORC1 inhibitor among in vitro endometrial cancer stem cell-enriched spheroid cells from clinical specimens. The in vitro sensitivity was consistent with the effects observed in in vivo spheroid-derived xenograft tumor models. Our findings revealed a complementary suppressive effect on endometrial cancer spheroid cell growth with the combined use of aldehyde dehydrogenase (ALDH) and PI3K-Akt inhibitors. In the PI3K-Akt-mTORC1 signaling cascade, the influence of ALDH on mTORC1 was partially channeled through retinoic acid-induced lactate dehydrogenase A (LDHA) activation. LDHA inhibition was found to reduce endometrial cancer cell growth, aligning with the effects of mTORC1 inhibition. Building upon our previous findings highlighting ALDH-driven glycolysis through GLUT1 in uterine endometrial cancer spheroid cells, curbing mTORC1 enhanced glucose transport via GLUT1 activation. Notably, elevated LDHA expression correlated with adverse clinical survival and escalated tumor grade, especially in advanced stages. Collectively, our findings emphasize the pivotal role of ALDH-LDHA-mTORC1 cascade in the proliferation of endometrial cancer. Targeting the interaction between mTORC1 and ALDH-influenced glycolysis holds promise for developing novel strategies to combat this aggressive cancer., (© 2024. The Author(s).)

Laparoscopic surgery has been used to treat gastric submucosal tumors (SMTs). Laparoscopic and endoscopic cooperative surgery (LECS) has been used when subtotal resection has been difficult, which enabled resection of these tumors. In this study, we reviewed the medical records of patients with gastric SMTs who underwent laparoscopic surgery in our hospital with the aim of reporting the surgical indications, procedures (especially for LECS), and outcomes of surgery. This study involved 55 patients who underwent laparoscopic surgery between April 2014 and March 2021. We classified the patients into two groups: laparoscopy-assisted surgery group (non-LECS group, n = 30) and LECS group (n = 25). LECS was performed in the upper stomach, in the greater curvature of the lower stomach, and in both intraluminal and intramural locations in the middle stomach. Non-LECS was selected for extraluminal and intramural tumors in the greater curvature of the upper stomach. There were no severe complications associated with the operation. There was one postoperative complication in the LECS group. The length of postoperative hospital stay did not significantly differ between the LECS and non-LECS groups. We reported the surgical procedures for gastric SMTs in our hospital. It is essential to make full use of the multiple techniques reported in this article and examine the location of the tumor to avoid excess or insufficient resection. Our review of the present case series allowed us to select the appropriate surgical approach for gastric SMTs based on the lesion location and type of development., (© 2024. The Author(s).)

Four subtypes of ovarian high-grade serous carcinoma (HGSC) have previously been identified, each with different prognoses and drug sensitivities. However, the accuracy of classification depended on the assessor's experience. This study aimed to develop a universal algorithm for HGSC-subtype classification using deep learning techniques. An artificial intelligence (AI)-based classification algorithm, which replicates the consensus diagnosis of pathologists, was formulated to analyze the morphological patterns and tumor-infiltrating lymphocyte counts for each tile extracted from whole slide images of ovarian HGSC available in The Cancer Genome Atlas (TCGA) data set. The accuracy of the algorithm was determined using the validation set from the Japanese Gynecologic Oncology Group 3022A1 (JGOG3022A1) and Kindai and Kyoto University (Kindai/Kyoto) cohorts. The algorithm classified the four HGSC-subtypes with mean accuracies of 0.933, 0.910, and 0.862 for the TCGA, JGOG3022A1, and Kindai/Kyoto cohorts, respectively. To compare mesenchymal transition (MT) with non-MT groups, overall survival analysis was performed in the TCGA data set. The AI-based prediction of HGSC-subtype classification in TCGA cases showed that the MT group had a worse prognosis than the non-MT group (P = 0.017). Furthermore, Cox proportional hazard regression analysis identified AI-based MT subtype classification prediction as a contributing factor along with residual disease after surgery, stage, and age. In conclusion, a robust AI-based HGSC-subtype classification algorithm was established using virtual slides of ovarian HGSC., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis., Methods: In a sub-analysis of a multicenter case-control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon., Results: Among the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS., Conclusion: RCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs., (© 2024. The Author(s).)

Objective: This study aimed to understand the effectiveness of regular care in reducing the incidence of severe peristomal skin disorders, as well as to identify their risk factors., Summary Background Data: Peristomal skin disorders occur frequently in outpatient settings and require appropriate intervention. It remains, however, to be demonstrated when the need to follow up these patients decreases and whether assessing severity of peristomal skin disorders is useful., Methods: This prospective, multicenter, observational cohort study was conducted in six regional high-volume Japanese hospitals. The primary endpoint of the study was the effectiveness of regular follow-up in reducing the incidence of severe peristomal skin disorders via a scoring system at a defined regular outpatient visit. Propensity score matching was performed to compare a control group and patients with severe peristomal skin disorders., Results: In total, 217 patients between December 2019 and December 2021 were enrolled, and 191 patients were analyzed. Multivariate analysis showed that loop stoma (odds ratio [OR], 5.017; 95% confidence interval [CI], 1.350-18.639; P=0.016) and stoma height of <10 mm (OR, 7.831; 95% CI, 1.760-34.838; P=0.007) were independent risk factors for all peristomal skin disorders. After propensity score matching, the incidence of the disorders was not significantly different between the specified evaluation timing and historical control groups (75.7% vs. 77.2%, P=0.775), and the incidence of the severe disorders based on the ABCD and DET scores (5.9% vs. 19.1%, P<0.001 and 1.5% vs. 29.4%, P<0.001, respectively) was significantly lower in the specified evaluation timing group than in the historical control group., Conclusion: Regular peristomal skin disease follow-up and scoring, as well as appropriate stoma care at the stoma outpatient visit did not change the frequency of peristomal skin disease, but severe peristomal skin disorders were prevented. Additionally, risk factors for peristomal skin disorders were found to be height <10 mm and loop stoma., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hospital treatment volume affects survival in patients with endometrial cancer; notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan., Methods: A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and high-volume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses., Results: A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000 with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or low-volume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and low-risk groups, respectively., Conclusion: Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer., Competing Interests: Honorarium, Bristol Myers Squibb (H.M) and none for others., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Recently, there has been a significant increase in the utilization of self-expandable metallic stents (SEMSs) for treating malignant colorectal obstructions through colorectal stenting. The mechanical properties of SEMSs are usually considered to affect clinical outcomes of patients with malignant colorectal obstructions. Methods : This single-arm, prospective, multicenter study of SEMS with a lower axial force and high axial force zero-border included 200 patients with malignant colorectal obstruction. Technical and clinical success, stent patency, and adverse events associated with SEMS placement were evaluated. Results: One patient was excluded, and 199 patients were evaluated. The treatment intent was bridge-to-surgery in 129 and palliation in 70 patients. Technical and clinical success rates were 99.5% and 97.0%, respectively. The percentage of the ColoRectal Obstruction Scoring System scores of 3 or higher improved significantly from 19.2% before placement to 93.9% after placement. Clinical success was not achieved in five patients due to insufficient stent expansion in four patients and stent occlusion in one patient. Only one patient underwent emergency surgery for perforation of the proximal colon, far from where the stent was placed; the rescue procedure was not performed, despite no improvement in proximal dilatation due to insufficient stent expansion. Among the palliation cohort, 15 patients received chemotherapy, including molecular-targeted agents such as bevacizumab. There were no fatal cases related to stent placement. Conclusions : For management of malignant colorectal obstruction, this newly developed SEMS with low axial force and a high axial force zero-border showed high technical and clinical success rates, and an extremely low perforation rate (0.5%).

To regulate the effective photon energy with a constant tube voltage and to perform enhanced K-edge x-ray imaging, we built a prototype fully digitalized triple-energy x-ray computed tomography (TECT) scanner utilizing beam hardening. An object on the turntable is irradiated by a 0.1-mm-focus x-ray tube at 1.4-time-magnification. 720 raw radiograms are obtained using a flat panel detector, and 512 tomograms are reconstructed. With an increasing digital amplification factor, the gray raw-density projections obtained using low-energy-photon absorption disappeared at a constant maximum raw density, and the effective energy was increased by x-ray beam hardening. TECT was performed at digital amplifier factors below 3.0, and the effective energy increased with increasing amplification factors. In particular, fine blood vessels were visible using gadolinium-K-edge CT., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody-drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively ( p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.

Introduction There has been no study on bone structural properties in postmenopausal women with rheumatoid arthritis (RA) in Japan. This study investigated bone mineral density (BMD) and bone structural properties in Japanese postmenopausal women with RA. Methods The study had a cross-sectional design and included 119 postmenopausal women aged 50-80 years with RA symptoms for more than five years. BMD, trabecular bone score (TBS), and results of hip structure analysis (HSA) were measured on dual-energy X-ray absorptiometry scans. The control group consisted of 288 women aged 50-80 years without RA. The RA group and control group using bisphosphonates were compared after propensity score matching for age, body mass index, and fracture history. Women in the RA group were also compared according to the use of glucocorticoids (GCs). Results After the propensity matching score, there were no other significant differences in BMD, TBS, and HSA parameters between the RA group and the control group. In the RA group, the TBS was lower in patients on GCs than those not on GCs (1.272 vs 1.313, p=0.008). There were no other significant differences in BMD and HSA parameters between patients in the RA group according to the use of GCs. Conclusion Although there were no differences in BMD, the TBS was lower in patients on GCs than those not on GCs in the RA group. It is thus important for physicians who administer GCs to treat patients with RA to be aware of not only BMD but also TBS., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Mima Hospital issued approval R2023.1-1. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Omichi et al.)

Purpose: The mortality rate for non-occlusive mesenteric ischemia remains high even after patients survive the acute postoperative period with tremendous treatment efforts, including emergency surgery, which is challenging. The aim of this study was to explore the preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia., Methods: This single-center, retrospective cohort study included patients diagnosed with non-occlusive mesenteric ischemia who underwent emergency surgery between August 2014 and January 2023. All patients were divided into survival-to-discharge and mortality outcome groups at the 90-day postoperative follow-up. Preoperative factors, including comorbidities, preoperative status of vital signs and consciousness, blood gas analysis, blood test results, and computed tomography, were compared between the two groups., Results: Twenty patients were eligible, and 90-day mortality was observed in 10 patients (50%). The mortality outcome group had significantly lower HCO3- (20.9 vs. 14.6, p = 0.006) and higher lactate (4.4 vs. 9.4, p = 0.023) levels than did the survival outcome group. The median postoperative time to death was 19 [2-69] days, and five patients (50%) died after postoperative day 30, mainly because hemodialysis was discontinued because of hemodynamic instability in patients requiring hemodialysis., Conclusion: Low preoperative HCO3- and high lactate levels may be preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia. However, patients on hemodialysis die from discontinuing hemodialysis even after surviving the acute postoperative phase. Therefore, indications for emergency surgery in patients with risk factors for postoperative mortality should be carefully determined., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: To perform energy-dispersive X-ray imaging, we constructed a photon-counting X-ray computed tomography (CT) scanner to perform enhanced K-edge CT., Methods: X-ray photons penetrating through an object were detected using a cadmium telluride flat panel detector (FPD) with pixel dimensions of 100 × 100 mm 2 , and 720 radiograms from the FPD were sent to the personal computer to reconstruct tomograms. Gadolinium (Gd) K-edge energy is 50.2 keV, and Gd-Kedge CT was carried out using photons with an energy range of 50-100 keV., Results: Compared with low-energy CT of 15-50 keV, the gray density of muscle and bone substantially decreased, and the image contrast of Gd media was improved utilizing Gd-K-edge CT., Conclusion: Using the cone beam, the effective pixel dimensions were 80 × 80 μm 2 , and blood vessels were observed at a high contrast using Gd-Kedge CT., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Medical Physics.)

Introduction: Cancer tissue absorbs 3-8 times more glucose than normal tissue. Therefore, we developed a gadobutrol-glucose solution for 7.0T magnetic resonance imaging to visualize whole cancerous regions at high contrast., Methods: The contrast medium consists of gadobutrol and glucose solutions, and these solutions are mixed before the vein infusion. We used readily available solutions, and the concentrations of the gadobutrol and glucose solutions were 60% and 5.0%, respectively. To visualize the cancerous region, we used two rabbits with VX7 thigh cancer. First, vein injection was carried out using a gadobutrol-saline solution containing 0.3 ml gadobutrol, and T1-weighted imaging (T1WI) was performed. Twenty-four hours after the first experiment, we performed T1WI of the VX7-cancer region using 50.3 mL gadobutrol-glucose solution including 0.3 ml gadobutrol., Results: Compared with T1WI using the gadobutrol-saline solution, the signal intensity of the cancerous region substantially increased using the gadobutrol-glucose solution., Conclusion: We confirmed significant signal-intensity increases in the whole VX7-cancer region of a rabbit thigh utilizing vein infusion of gadobutrol-glucose solution since the gadobutrol molecules were absorbed throughout the cancerous region along with glucose molecules., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Medical Physics.)

To observe fine blood vessels as uneven tomographic images at a high contrast, we performed tentative experiments on embossed x-ray computed tomography (CT). We constructed a cone-beam CT scanner and carried out dual-energy CT with tube voltages of 60 and 100 kV. X-ray photons penetrating through an object were detected using an indirect-conversion flat panel detector, and radiograms were produced and sent to a personal computer to reconstruct tomograms. Embossed CT was performed using pixel-shifted dual-energy subtraction, and blood vessels filled with Gd medium were observed as uneven images at high contrast and spatial resolutions. Using 1.4-time magnification imaging in combination with a 0.1-mm-focus x-ray tube, the diameter of the object visible on the embossed CT was below 100 μm., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Self-oscillating gel systems exhibiting an expanded operating temperature and accompanying functional adaptability are showcased. The developed system contains nonthermoresponsive main-monomers, such as N,N-dimethylacrylamide (DMAAm) or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or acrylamide (AAm) or 3-(methacryloylamino)propyl trimethylammonium chloride (MAPTAC). The gels volumetrically self-oscillate within the range of the conventional (20.0 °C) and extended (27.0 and 36.5 °C) temperatures. Moreover, the gels successfully adapt to the environmental changes; they beat faster and smaller as the temperature increases. The period and amplitude are also controlled by tuning the amount of main-monomers and N-(3-aminopropyl) acrylamide. Furthermore, the record amplitude in the bulk gel system consisting of polymer strand and cross-linker at 36.5 °C is achieved (≈10.8%). The study shows new self-oscillation systems composed of unprecedented combinations of materials, giving the community a robust material-based insight for developing more life-like autonomous biomimetic soft robots with various operating temperatures and beyond., (© 2024 The Authors. Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.

Background: A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited., Objective: We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods., Methods: In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845., Results: The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period., Conclusions: We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

Emergent properties accompanying synchronization among oscillators are vital characteristics in biological systems. Belousov-Zhabotinsky (BZ) oscillators are an artificial model to study the emergence and synchronization in life. This research represents a self-oscillating gel system with clusterable properties to experimentally examine synchronous and emergent properties at a fundamental hierarchical level. Incorporating acrylic acid (AAc) moieties within the gel network facilitates cluster formation through hydrogen bonding in an acidic BZ substrate solution. Upon clustering, both homogeneous and heterogeneous gel assemblies─ranging from double to quadruple clusters─exhibit increased and synchronized periods and amplitudes during the BZ reaction. Notably, in heterogeneous clusters, gel units with initially short periods and small volumetric amplitudes display a significant increase, aligning with the lonfger periods and larger amplitudes of other elements within the cluster, an emergent property. This research can pave the way for a better understanding of synchronous and emergent properties in biological oscillators such as cardiomyocytes.

Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1α induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1α induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC., Competing Interests: Declaration of interests Teikyo University has filed for a patent application on CAF inhibition by tyrosine kinase inhibitors, and K.O. and Y.M. are named as inventors on this patent., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Superior mesenteric venous thrombosis (SMVT) is mostly treated with anticoagulation therapy; however, SMVT can lead to irreversible bowel ischemia and require bowel resection in the acute or subacute phase., Case Presentation: We report four cases of SMVT that required careful observation and bowel resection. Case 1: A 71-year-old man presented with abdominal pain, diarrhea, and vomiting that showed a completely occluded SMV with thrombus and small bowel ischemia. Case 2: A 47-year-old man presented with abdominal pain, peritoneal irritation symptoms, and a completely occluded SMV with thrombus, ischemia of the small bowel, and massive ascites. Case 3: A 68-year-old man presented with abdominal pain and vomiting for several days and showed a partially occluded SMV with a thrombus, bowel ischemia, and massive ascites. Case 4: A 68-year-old man presented with acute abdominal pain and a partially occluded SMV with thrombus and bowel edema without ischemic changes. Anticoagulation therapy was administered; however, 3 days later, abdominal pain and bowel ischemia worsened. Bowel resection was performed in all cases., Conclusions: Most idiopathic SMVT cases can be treated with anticoagulation therapy or endovascular thrombectomy. However, in cases with peritoneal irritation signs, these treatments may be ineffective, and bowel resection may be required., (© 2024. The Author(s).)

Recent reports have focused on the usefulness of conversion surgery, in which chemotherapy is given to patients with unresectable advanced gastric cancer (GC), and radical surgery is subsequently performed if resection becomes possible; however, no consensus has been reached regarding the usefulness of this strategy. We report on a 74-year-old man who was diagnosed with esophagogastric junction cancer (T3N3M1 (LYM): stage IV). Chemotherapy was chosen and seven courses of S1 + cisplatin (SP) + trastuzumab (HCN) and two courses of S1 + HCN were administered. Approximately 10 months after the start of chemotherapy, the tumor had almost disappeared and we therefore decided to perform conversion surgery. Pathologic examination of the specimen and dissected lymph nodes showed no cancer. Postoperatively, the patient underwent chemotherapy until the second postoperative year, and no metastasis or recurrence was observed for nine years after surgery. Conversion surgery after chemotherapy resulted in recurrence-free survival in this case; however, further studies are needed to elucidate the effect of surgery after chemotherapy for patients with stage IV GC, as chemotherapy continues to evolve., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Enomoto et al.)

We aimed to investigate the differences in renal function between patients who underwent single inner-layer renorrhaphy (SILR) or double-layer renorrhaphy (DLR) among those with renal tumors who underwent robot-assisted partial nephrectomy (RAPN). This retrospective multicenter cohort study was conducted between November 2018 and October 2023 at two institutions and included patients who underwent RAPN. In total, 93 eligible patients who underwent RAPN were analyzed. Preoperative renal function and prevalence of chronic kidney disease were not significantly different between the two groups. Although urinary leakage was observed in three patients (5.9%) in the SILR group, there was no significant difference between the two groups regarding surgical outcomes ( p = 0.249). Serum creatinine levels after RAPN were significantly lower in the SILR group than in the DLR group on postoperative days 1 and 365 following RAPN ( p = 0.04). The estimated glomerular filtration rate (eGFR) was significantly lower in the DLR group than in the SILR group only on postoperative day 1; however, there was no significant difference between the two groups thereafter. Multivariate analysis showed that the method of renorrhaphy was not a predictor for maintaining renal function after RAPN even though it was associated with eGFR on postoperative day 1.

Background: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes., Objective: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs)., Methods: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps., Results: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo., Conclusion: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)