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Wnt/ß-catenin signaling is considered to be an essential regulator of adrenocortical oncogenesis. Wnt inhibitory factor-1 (Wif-1), an extracellular regulator of Wnt signaling, is frequently down-regulated by hypermethylation of the promoter CpG. We investi

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase ( FH ) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal cell carcinoma (RCC). HLRCC-associated RCC is aggressive and diagnosed at a much earlier age than sporadic RCC. It is essential for carriers of HLRCC to undergo annual renal screening by magnetic resonance imaging to detect early stage RCCs. Metastatic HLRCC-associated RCC must be treated by systemic therapy; however, it is unclear which medicines are most effective in treating this cancer owing to its low incidence rate. Immune checkpoint inhibitor (ICI) combinations or ICIs plus tyrosine kinase inhibitors are administered as systemic therapy for clear cell RCC. Here, we report a patient with HLRCC-associated RCC treated with sequential therapy, including ipilimumab plus nivolumab combination and cabozantinib, after diagnosis of HLRCC-associated RCC using FoundationOne Liquid CDx and single-site analysis. We also investigated familial FH mutations and describe a new family pedigree for HLRCC., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press.)

Background and Aims: Research suggests that various psychosocial factors influence chronic pain, with psychotherapies like cognitive behavioral therapy  proving effective. However, the limited availability and accessibility have prolonged suffering among patients with chronic pain. This challenge has led to a growing demand for accessible online interventions. We developed an online cognitive behavioral group therapy (CBGT) program, building upon our existing face-to-face CBGT program. We compared the scores obtained by patients during the treatment-as-usual (TAU) period with those collected at the beginning and at the end of the intervention., Methods: Patients with chronic pain ( N  = 22) agreed to participate in the online CBGT program, which was conducted once a week for 12 sessions. The sample size was decided based on the effect sizes of our past face-to-face CBGT. We assessed pain intensity [Visual Analogue Scale (VAS)], pain catastrophizing [pain catastrophizing scale (PCS)] and psychiatric assessment [Beck Depression Inventory-Second Edition (BDI)-II], State-Trait-Anxiety Inventory (STAI), and Short Form Health Survey (SF-36) at three points: entry, pretreatment, and posttreatment. We also evaluated the participants' therapeutic alliance with the treatment staff [short-form version of the Working Alliance Inventory (WAI-S)]. We utilized analyses of variance, Friedman test, paired t -tests, Wilcoxon signed-rank test, and Pearson correlation analysis for data evaluation., Results: Results indicated a significant posttreatment improvement in VAS, PCS, and BDI-II scores compared to the TAU period. Furthermore, posttreatment WAI-S scores increased significantly compared to pretreatment scores. Also, positive correlations were observed among pre- and posttreatment changes in WAI-S, pain intensity, and pain catastrophizing scores., Conclusion: There is a possibility that a therapeutic alliance can be established, and therapeutic effects achieved through an online CBGT intervention; however, additional research is required to substantiate this potential. We have registered this clinical trial in UMIN-CTR on 04/21/2021 with the number UMIN000043982., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor type, and ruptured pancreatic tumors are rarer. Computed tomography (CT) in a 48-year-old man incidentally revealed a raptured pancreatic tail tumor. The patient was treated conservatively because he was asymptomatic, and his general condition was stable. After a detailed examination, the pancreatic tumor was diagnosed as raptured PACC. Considering the potential infiltration of tumor cells into the hematoma within the omental sac, our decision is to initiate chemotherapy as the primary course of action. A liquid biopsy was performed, and comprehensive genomic profiling of circulating tumor DNA showed a tumor BRCA2 mutation. Chemotherapy with modified FOLFIRINOX (mFFX) was selected as the first treatment. After seven courses of mFFX, the primary tumor diminished remarkably. At this time, the radical resection was performed via distal pancreatectomy with simultaneous resection of the gastric wall and colon, which had adhered strongly to the tumor. Histopathological examination revealed that the tumor had shrunk to less than 5% of its original size due to chemotherapy (Grade 3 of Evans Classification). Devising treatment strategies for ruptured pancreatic malignant tumors is challenging due to the worsening general condition caused by severe abdominal symptoms and intra-abdominal bleeding. In this context, this case-report documents a rare instance of raptured PACC with a tumor BRCA2 mutation that underwent radical resection following mFFX treatment., Competing Interests: Conflict of interestThe authors declare no conflict of interest for this article., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC)., Methods: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide., Results: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients., Conclusions: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the efficacy of continuous suturing using barbed suture for vesicourethral anastomosis (VUA) during robot-assisted laparoscopic radical prostatectomy (RARP)., Materials and Methods: Seventy-three consecutive patients who underwent RARP by a single surgeon between 2020 and 2022 were retrospectively divided based on the suture type used for VUA: group A, 3-0 poliglecaprone-25 RB-1 needle (Monocryl®), n = 46; group B, 3-0 spiral polydioxanone (PDS) barbed suture with RB-1 needle (STRATAFIX®), n = 27., Results: There was no significant difference in patient background characteristics between groups, including age, body mass index, and clinical stage. However, group B had a significantly shorter operative time, console time, hospital stay, and duration of urethral catheterization. The VUA time was significantly shorter in group B than in group A (17.9 min vs. 10.6 min; p < 0.001). Only 1 case of minor leakage was observed during the intraoperative leak test (1 patient in group A). There was no significant difference in the number of pads used at 1, 3, 6 months and 1 year postoperatively. There were no urethral strictures, and there was no significant difference in pathologic results or postoperative prostate-specific antigen progression between groups., Conclusions: Our study suggests that the use of barbed suture during VUA for RARP is associated with reduced VUA time., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: A bridge to surgery (BTS) using self-expandable metallic stents (SEMSs) is becoming the primary treatment for obstructive colorectal cancer (OCRC). In Japan, intestinal decompression was usually performed using decompression tubes (DTs). However, few reports have compared the outcomes of SEMS and DTs as BTS. Therefore, we compared the treatment outcomes of SEMS and DTs for OCRC., Methods: Data of 80 patients who underwent radical resection after endoscopic decompression for stage II or III OCRC between 2007 and 2021 were retrospectively analyzed. Patients were divided into two groups based on whether they received SEMS (n = 53) or DTs (n = 27)., Results: The clinical success rate of decompression was 96.2% and 88.9% in the SEMS and DT groups, respectively. Additionally, 96.2% of patients who received SEMS were able to resume their routine diet without stricture symptoms. The rate of stoma construction and incidence of postoperative complications were lower in the SEMS group (p < 0.005 and p < 0.01, respectively). The 3-year relapse-free survival rates were 71.9% and 51.2% in the SEMS and DT groups, respectively, which were not significantly different (p = 0.10)., Conclusion: BTS using SEMS might be an adequate treatment for stage II or III OCRC regardless of tumor location owing to the comparable oncological outcomes with DT and low perioperative complication rate., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

A 41-year-old male consulted a local doctor with fever and left flank pain. He was introduced to our hospital for a left renal mass detected by ultrasonography. Blood analysis revealed elevated white blood cell count, C-reactive protein, bilirubin and aspartate transaminase. Computed tomography demonstrated a left renal mass (expansive growth), which was 11 cm in maximum diameter and enhanced moderately at the corticomedullary phase. Neither distant metastasis, infectious findings nor hepatobiliary abnormalities were observed. The patient underwent laparoscopic radical nephrectomy with a clinical diagnosis of non-clear cell renal cell carcinoma cT2bN0M0 with Stauffer syndrome. The surgery required 186 minutes of insufflation, and estimated blood loss and specimen weight were 44 ml and 695 g, respectively. There were no complications. Histopathological diagnosis was chromophobe renal cell carcinoma-classic pattern (ChRCC-C), which was producing interleukin-6 in the tumor cytoplasm immunohistochemically. Postoperatively, there was early defervescence with complete resolution of the Stauffer syndrome. No relapse or liver dysfunction has occurred at 5 years after operation. To our knowledge, this is the first reported case in the literature of ChRCC accompanied by Stauffer syndrome.

Objectives: The purpose of this study was to deepen our understanding of pitches and to obtain basic knowledge about pitches by comparing 4-seam and other pitches in Major League Baseball (MLB)., Methods: We analyzed big data for 1,820 professional baseball pitchers of MLB on release speed, spin rate, release point 3D coordinates (X, Y, and Z axes), amount of change for 4-seam, and seven changing ball types (sinker, slider, changeup, cutter, curve, split finger, and knuckle curve), using PITCHf/x and TrackMan. We also evaluated three relationships: (1) between the release points and the ball types of pitch; (2) between the amount of change in the ball and the release speed; and (3) between the release speed and the spin rate., Results: The release speed was significantly slower in seven changing ball types than in the 4-seam ( p  < 0.01, respectively). The spin rate and the amount of change (ΔX and ΔZ) were significantly different between 4-seam and seven changing ball types ( p  < 0.01, respectively). Release point 3D coordinates (X, Y, and Z axes) were significantly different between 4-seam and slider, cutter, and curve ( p  < 0.01, respectively). Based on these findings, the eight pitch types were mainly divided into three groups: 4-seam, curve, and off-speed pitch types., Conclusion: Seven changing ball types included specific characteristics for each parameter. The correspondence among the release speed, ΔX, and ΔZ at the 3D coordinates is an arch with 4-seam as the apex. Our results suggest an effective strategy for changing the release point and displacement of a ball's trajectory to improve the performance of baseball pitchers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Hashimoto, Nagami, Yoshitake and Nakata.)

Aims: Serum uric acid increases with metabolic disorders; however, whether the effects of uric acid on atherosclerosis are different in females and males has not been sufficiently evaluated. Therefore, this study compared the impact of uric acid on arterial stiffness and atherosclerosis between females and males., Methods: We enrolled 10196 untreated middle-aged subjects (46±8 years, 3021 females and 7175 males) who underwent periodic health check-ups. Serum uric acid levels were measured and arterial stiffness and atherosclerosis were assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and plaque, using ultrasound imaging., Results: Females with increased arterial stiffness (CAVI ≥ 8.0) or carotid plaques had higher uric acid than those without (P＜0.0001), but males did not. In multivariable regression analyses including overall participants, uric acid was significantly associated with the CAVI, where sex interacted with uric acid. In sex-specific analyses, uric acid was significantly associated with the CAVI, but not with carotid IMT, in both sexes. However, logistic regression analyses revealed that serum uric acid was independently associated with the presence of carotid plaques in females. The exclusion of subjects with abdominal obesity or metabolic syndrome from the analysis did not alter the results in females., Conclusions: Serum uric acid was significantly associated with the CAVI in both sexes, but the interaction of sex was confirmed and associated with a carotid plaque only in females. These findings support the increased impact of serum uric acid on arterial stiffness and atherosclerosis in females.

Background: Apalutamide-associated skin adverse events are more common in the Japanese than in the global population. However, limited clinical data have hampered further understanding. This real-world study investigated the clinical characteristics of skin adverse events in patients with advanced prostate cancer., Methods: We retrospectively reviewed 119 patient records from 16 institutions in Japan. Skin adverse events were graded according to the Common Terminology Criteria for Adverse Events (v5.0). The incidence and characteristics of skin adverse events (along with the clinical risk factors for their incidence, worsening, and recurrence) were evaluated., Results: Fifty-five patients (46.2%) experienced skin adverse events. The median times to the incidence and remission of skin adverse events were 62 and 30 days, respectively. Grade 3 skin adverse events were observed in 15 patients (12.6%). The median time from the first incidence to apalutamide interruption was significantly longer in patients with progression to grade 3 skin adverse events than in those without such a progression (8 vs. 0 days, p = 0.005). Skin adverse events were observed in 45.2% of patients who resumed apalutamide treatment (median treatment interruption time: 31.5 days). Sixteen patients (13.4%) permanently discontinued apalutamide due to skin adverse events. No significant clinical risk factors for the incidence, worsening and recurrence of apalutamide-associated skin adverse events were observed., Conclusions: Nearly half of the Japanese patients in this study experienced skin adverse events following apalutamide administration. The time to apalutamide discontinuation after the incidence of skin adverse events was positively correlated with the worsening of these events., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

Aims: Small arteries can be visualized in the ocular fundus, and findings of retinopathy based on Scheie classification are often applied to evaluate the impact of hypertension and atherosclerosis. However, the relationship between damage in the large and small arteries has not been investigated sufficiently, especially in the early stages. The present study investigated possible associations between large artery atherosclerosis and small artery retinopathy in untreated middle-aged individuals., Methods: Untreated middle-aged workers undergoing periodic health check-ups (n=7,730, 45±8 years) were enrolled in this study. The absence or presence and extent of retinopathy were characterized by ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4) based on Scheie classification. Large artery atherosclerosis was examined based on functional assessment of the cardio-ankle vascular index (CAVI) and morphological assessment of the carotid intima-media thickness (IMT) by ultrasound., Results: We found significant differences in CAVI and carotid IMT between individuals with and without hypertensive or atherosclerotic retinopathy. Multivariable regression analysis showed that the presence of hypertensive and atherosclerotic retinopathy was significantly associated with CAVI and carotid IMT. Logistic regression analysis with the endpoint of a hypertensive or atherosclerotic lesion revealed that CAVI and carotid IMT are independent determinants of retinopathy., Conclusions: CAVI and carotid IMT were significantly associated with the presence of retinopathy based on Scheie classification in untreated middle-aged subjects, implying that atherosclerotic examination in large arteries could reveal early-stage small artery retinopathy.

Background: A body shape index (ABSI) is a novel anthropometric measure calculated using waist circumference (WC), body mass index (BMI), and body height. This study investigated the usefulness of ABSI to identify individuals with metabolic syndrome (MetS) and increased arterial stiffness in the middle-aged population., Methods: Middle-aged workers who underwent periodic health check-ups and who were without previous cardiovascular events were enrolled (n = 10,182). In addition to ABSI, visceral fat area (VFA) was evaluated using computed tomography. Obesity and MetS were diagnosed on the basis of WC, VFA, and ABSI. Arterial stiffness was examined by measuring the cardio-ankle vascular index (CAVI)., Results: ABSI was significantly associated with CAVI in multivariable regression analysis. Logistic regression analysis revealed that ABSI was independently associated with the presence of MetS diagnosed on the basis of WC or VFA after adjustment for potential confounders, including BMI. Subjects with MetS diagnosed on the basis of each obesity index showed higher CAVI values than those without. Among subjects with MetS diagnosed on the basis of WC or VFA, those with MetS who met the definition of ABSI obesity showed significantly higher CAVI than those who did not. The other logistic regression analysis demonstrated that CAVI was independently associated with MetS defined on the basis of ABSI., Conclusions: ABSI was significantly associated with CAVI and the presence of MetS in the middle-aged population and helped to discriminate individuals with MetS and increased CAVI. ABSI could serve to identify individuals with MetS and increased arterial stiffness., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Medial elbow apophysitis is a traction apophysitis observed in the medial epicondyle of the elbow in preadolescent baseball players. The purpose of this study was to determine the relationship between medial elbow apophysitis and elbow valgus instability in preadolescent baseball players., Methods: The participants were classified into a control group and an injury group; the injury group included participants diagnosed with a medial elbow injury (inclusion criteria were only symptoms of the elbow joint or positive findings on physical examinations, or both). Elbow valgus instability was assessed by measuring the differences in ulnohumeral joint gapping width, with and without gravity stress induced by weight loading of the forearm using ultrasonography., Results: The control and injury groups consisted of 81 and 23 preadolescent baseball players, respectively. In the throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (1.07 vs. 0.57 mm, P  = .001). In the non-throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (0.57 vs. 0.37 mm, P  = .011). The area under the curve for valgus instability of the throwing elbow was 0.89 mm (95% confidence interval, 0.64-0.77), and the cut-off value for elbow pain appearance was 0.80 mm., Conclusion: The increased elbow valgus instability in the injury group was associated with a medial elbow injury. For the elbow valgus instability of the non-throwing side in the injury group, we considered that players with medial elbow apophysitis inherently have elbow laxity., (© 2021 The Authors.)

When we have rehearsed a movement using an object, we can reproduce the movement without holding the object. However, the reproduced movement sometimes differs from the movement holding a real object, likely because movement recognition is inaccurate. In the present study, we tested whether the recognition capability was dissociated from the acquisition of motor skill memory. Twelve novices were asked to rotate two balls with their right hand as quickly as possible; they practiced the task for 29 days. To evaluate recognition capability, we calculated the difference in coordination pattern of all five digits between the ball-rotation movement and the reproduced movement without holding balls. The recognition capability did not change within the first day, but improved after one week of practice. On the other hand, performance of the ball rotation significantly improved within the first day. Since improvement of performance is likely associated with acquisition of motor skill memory, we suggest that recognition capability, which reflects the capability to cognitively access motor skill memory, was dissociated from the acquisition of motor skill memory. Therefore, recognition of one's own skilled movement would rely on a hierarchical structure of acquisition of motor skill memory and cognitive access to that memory., (© 2021. The Author(s).)