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Background: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear., Methods: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves., Results: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck., Conclusions: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC., Patients and Methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer., Results: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively)., Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS., (© 2024 BJU International.)

Background: Osteochondral lesions of the talus (OLTs) are among the common sports-related injuries. However, there are few reports on the return to sports after OLT surgery in skeletally immature children. This study was performed to evaluate the return to sports after microfracture for OLTs in skeletally immature children., Methods: This study involved 17 ankles of 16 patients (mean age, 13.2 years; range, 10-16 years) with open tibial epiphyses on magnetic resonance imaging (MRI) who underwent microfracture for OLTs <10 mm in diameter and confirmation of lesion instability under arthroscopy. Nine of 17 ankles had additional lateral ankle ligament stabilization. All patients were participating in some form of sports. The Japanese Society for Surgery of the Foot (JSSF) score, Ankle Activity Score (AAS), return to sports rate, lesion size, grade of subchondral bone marrow edema, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score on MRI were evaluated after microfracture. The mean postoperative follow-up period was 53.5 months., Results: The mean JSSF score significantly improved from 76.1 points preoperatively to 94.9 points at the final follow-up ( P  < .01). The mean AAS showed no change from preoperative state to final follow-up. The return to sports rate was 100%. The lesion size significantly decreased from 76.3 to 56.7 mm 2 in area ( P  = .02) and from 283.2 to 185.6 mm 3 in volume ( P  = .05). The bone marrow edema grade decreased in 8 of 17 ankles. The total MOCART score showed a significant improvement from 6 months to 1 year postoperatively ( P  = .05)., Conclusion: All skeletally immature children who underwent microfracture for OLTs in this study were able to return to sports activity and showed improvements in clinical scores and MRI parameters. Microfracture may be considered an effective first-line treatment for OLTs <10 mm in diameter in skeletally immature athletes., Level of Evidence: Level IV, retrospective case-control study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online.

Solid tumors as well as leukemias and lymphomas show striking changes in nuclear structure including nuclear size and shape, the number and size of nucleoli, and chromatin texture. These alterations have been used in cancer diagnosis and might be related to the altered functional properties of cancer cells. The nuclear matrix (NM) represents the structural composition of the nucleus and consists of nuclear lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. In the nuclear microenvironment, the NM is associated with multi-protein complexes, such as basal transcription factors, signaling proteins, histone-modifying factors, and chromatin remodeling machinery directly or indirectly through scaffolding proteins. Therefore, alterations in the composition of NM could result in altered DNA topology and changes in the interaction of various genes, which could then participate in a cascade of the cancer process. Using an androgen-sensitive prostate cancer cell line, LNCaP, and its androgen-independent derivative, LN96, conventional 2D-proteomic analysis of the NM proteins revealed that purine-rich element binding protein alpha (PURα) was detected in the NM proteins and differentially expressed between the cell lines. In this article, we will review the potential role of the molecule in prostate cancer.

Background: Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters., Methods: We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm 2 ]/height 2 [m 2 ]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes., Results: The median follow-up was 56.9 months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm 2 /m 2 )., Conclusions: Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

A 71-year-old man presented with exertional dyspnea. Chest radiography revealed multiple pulmonary nodules, and contrast-enhanced computed tomography showed findings suspicious of right renal pelvic cancer. Percutaneous lung tumor biopsy revealed a histological diagnosis of urothelial carcinoma, and right renal pelvic cancer cT3N2M1 was diagnosed. Favorable response was shown during primary chemotherapy with gemcitabine and cisplatin but resulted in tumor progression after four cycles. The patient was switched to a second-line treatment, pembrolizumab, which resulted in rapid tumor growth. Hyper-progression was suspected, and the patient was promptly switched to a third-line treatment, enfortumab vedotin. The tumor shrank significantly. After three treatment cycles, an adverse event of enteritis was observed. A biopsy of the intestinal mucosa led to a histopathologic diagnosis of late-onset immune-related adverse event; therefore, enfortumab vedotin could be continued.

Background: Robot-assisted radical cystectomy (RARC) with urinary diversion has become a standard surgical procedure because of its three-dimensional high-definition surgical field of view, flexibility, and stability. However, because of the highly complex steps of surgery, postoperative complications cannot be ignored., Methods: This retrospective, single-center, observational cohort study investigated the postoperative complications following RARC at a non-high-volume center in Japan. From August 2019 to March 2023, 50 consecutive patients who underwent RARC for histologically proven muscle-invasive bladder cancer (MIBC) or high-risk non-MIBC with an indication for radical cystectomy according to the Japanese Urological Association Guideline 2019 were included. Factors correlated with the selection of extracorporeal urinary diversion (ECUD) or cutaneous ureterostomy rather than intracorporeal urinary diversion (ICUD) for urinary diversion were also investigated., Results: In total, 33 (66%) and 31 (62%) patients experienced complications during the first 90 and 30 days after RARC, respectively. Among them, 19 (38%) and 18 (36%) patients developed Clavien-Dindo classification G2 complications, and 12 (24%) and 11 (22%) developed G3 or higher (major) complications during the first 90 and 30 days after RARC, respectively. The most common complications were gastrointestinal complications (26%) and urinary tract infections (22%). Nine patients (18%) underwent surgical intervention within 90 days of undergoing RARC. Higher infusion volume during the operations was significantly correlated with the occurrence of major complications within 90 days (P=0.025) and 30 days (P=0.0158) after RARC. Nineteen patients (38%) underwent non-ICUD. Twelve patients received ECUD as an ileal conduit or neobladder, and among them, three patients received ECUD due to intraabdominal adhesion for previous abdominal surgery or radiation, while four patients received ECUD ileal conduit due to comorbidities and advanced cases (palliative surgery) to shorten the surgery time., Conclusions: Surgical complications related to the initial experience with RARC at a non-high-volume center in Japan cannot be ignored. Although this complicated surgical procedure requires a learning curve to achieve a stable rate of much fewer major complications after RARC, careful assessment of patients' status before surgery and critical postoperative management may reduce complication rates more quickly, even at non-high-volume centers., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1234/coif). The series “Current Status of Robotic Surgery for Genitourinary Diseases in Japan” was commissioned by the editorial office without any funding or sponsorship. T.I. reports that he receives a grant (No. 21H03066) from JSPS KAKENHI. The authors have no other conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Background: This study aimed to elucidate the relationship between ankle morphology and the size of non-trauma related osteochondral lesions of the talus (OLT), because approximately half the OLT found in children is of unknown origin., Methods: 34 ankles in 30 skeletally immature children with OLTs who underwent preoperative magnetic resonance imaging (MRI) were evaluated. Parameters measured included area of the OLT, tibial axis-medial malleolus angle (TMM), malleolar width (MalW), and talar surface angle (TSA; defined as the angle between the line perpendicular to the mid-diaphysis of the tibia and the talar joint surface; medial inclination, positive). The ankles were divided into two groups: the trauma group had a history of injury and the idiopathic group had no history of injury. The correlation between lesion area and MRI parameters were evaluated in each group., Results: Thirteen ankles in 13 patients comprised the trauma group, while 21 ankles in 17 patients were in the idiopathic group. Of the 17 patients in the idiopathic group, four had bilateral OLT. In the trauma group, MalW was significantly correlated with the area (r = 0.827, P = 0.0001). In the idiopathic group, TMM and MalW were significantly correlated with the area (r = 0.608, P = 0.003 and r = 0.566, P = 0.008). TSA was positively correlated with area in the idiopathic group (r = 0.516, P = 0.017), but negatively correlated with area in the trauma group (r = -0.609, P = 0.027). The other parameters showed no significant correlation., Conclusions: The size of non-trauma related OLTs may have been affected by an ankle morphology showing poor bone conformity, such as an open medial malleolus and inclined talar joint surface. In addition, the evaluation of the contralateral ankle joint may be crucial when patients with OLT have no specific history of trauma., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this manuscript., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Various surgical treatments are available for a symptomatic AN, including percutaneous drilling (PD). PD is reportedly effective for ANs in skeletally immature children. However, no reports have described the foot alignment after PD in skeletally immature children. This study was performed to compare the radiographic parameters between the preoperative period and the final follow-up after PD for symptomatic ANs in skeletally immature children. From October 2013 to December 2020, PD was performed on 13 feet in 10 skeletally immature children. The patients comprised 5 boys and 5 girls with a mean age at surgery of 11.9 years. The mean follow-up period was 14.8 months. We measured 5 radiographic findings preoperatively and at the final follow-up: calcaneal pitch angle (CPA), talocalcaneal angle (TCA), talonavicular coverage angle (TNCA), anteroposterior talo-first metatarsal angle (ATMA), and lateral talo-first metatarsal angle (LTMA). Ten feet were assessed as excellent, 1 as fair, and 2 as poor. Ten unions (76.9%) were achieved among the 13 feet. The mean CPA improved from 16.4 ± 4.1 degrees preoperatively to 18.2 ± 3.4 degrees at the final follow-up, the TCA improved from 43.0 ± 3.7 to 45.2 ± 4.4 degrees, and the TNCA improved from 19.9 ± 4.4 to 15.4 ± 5.0 degrees (P < .05). The ATMA and LTMA were not significantly different between the preoperative period and final follow-up. We found that PD for symptomatic ANs in skeletally immature children was effective treatment, and some radiographic parameters showed significant differences between the preoperative period and final follow-up., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The glassy cytoplasm, crowded with bio-macromolecules, is fluidized in living cells by mechanical energy derived from metabolism. Characterizing the living cytoplasm as a nonequilibrium system is crucial in elucidating the intricate mechanism that relates cell mechanics to metabolic activities. In this study, we conducted active and passive microrheology in eukaryotic cells, and quantified nonthermal fluctuations by examining the violation of the fluctuation-dissipation theorem. The power spectral density of active force generation was estimated following the Langevin theory extended to nonequilibrium systems. However, experiments performed while regulating cellular metabolic activity showed that the nonthermal displacement fluctuation, rather than the active nonthermal force, is linked to metabolism. We discuss that mechano-enzymes in living cells do not act as microscopic objects. Instead, they generate meso-scale collective fluctuations with displacements controlled by enzymatic activity. The activity induces structural relaxations in glassy cytoplasm. Even though the autocorrelation of nonthermal fluctuations is lost at long timescales due to the structural relaxations, the nonthermal displacement fluctuation remains regulated by metabolic reactions. Our results therefore demonstrate that nonthermal fluctuations serve as a valuable indicator of a cell's metabolic activities, regardless of the presence or absence of structural relaxations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Background: Open repair of the Achilles tendon carries a risk of wound complications and infection. The Achilles tendon is covered by a thin layer of skin and subcutaneous tissue, which has a fragile blood supply. The full plantarflexion position may cause sustained blanching of the skin above the Achilles tendon. However, no reports have described the in vivo blood flow (BF) changes at the skin surface with ankle position. This study aimed to use laser Doppler flowmetry to evaluate the in vivo BF at the skin surface and thereby clarify the changes in BF with ankle position., Methods: The study cohort comprised 30 feet in 15 participants with no history of Achilles tendon rupture. Laser Doppler flowmetry was used to measure the BF at the skin surface above the medial Achilles tendon in the natural plantarflexion (NP) and full plantarflexion (FP) positions., Results: In the NP and FP positions, the BF at 5 cm proximal to the calcaneal insertion (frequent site of Achilles tendon rupture) was 1.50 ± 0.32 and 0.97 ± 0.28 mL/min/100 g, respectively ( P  < .0001)., Conclusion: The BF at the skin surface adjacent to the medial Achilles tendon at 5 cm proximal to the calcaneal insertion was significantly less in the FP position than the NP position., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online.

Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a treatment target for various cancers. In fact, polyadenosine diphosphatase ribose polymerase (PARP) inhibitors, such as olaparib (Lynparza ® ), have shown remarkable therapeutic efficacy against BRCA1/2 -mutant cancers through synthetic lethality. Recent genomic analytical advancements have revealed that BRCA1/BRCA2 pathogenic variants are the most frequent mutations among DDR genes in prostate cancer. Currently, the PROfound randomized controlled trial is investigating the efficacy of a PARP inhibitor, olaparib (Lynparza ® ), in patients with metastatic castration-resistant prostate cancer (mCRPC). The efficacy of the drug is promising, especially in patients with BRCA1/BRCA2 pathogenic variants, even if they are in the advanced stage of the disease. However, olaparib (Lynparza ® ) is not effective in all BRCA1/2 mutant prostate cancer patients and inactivation of DDR genes elicits genomic instability, leading to alterations in multiple genes, which eventually leads to drug resistance. In this review, we summarize PARP inhibitors' basic and clinical mechanisms of action against prostate cancer cells and discuss their effects on the tumor microenvironment., Competing Interests: The authors declare no conflict of interest.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi., (© 2023. The Author(s).)

Background: The effect of stretching on the mechanical properties of the plantar fascia (PF) remain unclear. This study was performed to determine the effect of PF-specific stretching (PFSS) and Achilles tendon stretching (ATS) on the viscoelastic properties of the PF with shear wave elastography (SWE)., Methods: We recruited 14 participants (8 men, 6 women) with no history of PF disorders or painful episodes. The mean age of the participants was 30.9 ± 4.8 (range, 25-41) years. All participants performed sustained PFSS (sPFSS) on one foot and intermittent PFSS (iPFSS) on the other foot. Two weeks later, all participants performed sustained ATS (sATS) on one foot and intermittent ATS (iATS) on the other foot. SWE measurements were performed immediately after each stretching., Results: The PF elasticity immediately before stretching ranged from 133.8 kPa to 144.7 kPa. The PF elasticity after stretching ranged from 158.9 kPa to 215.8 kPa. There was a significant increase in PF elasticity after sPFSS, iPFSS, sATS, and iATS (P < .01). The elasticity after sATS was greater than that after iATS (P = .03). In contrast, there were no differences in PF elasticity after stretching between sPFSS and iPFSS (P = .13), sPFSS and sATS (P = .17), or iPFSS and iATS (P = .50)., Conclusions: PF elasticity increased after stretching regardless of the frequency and type of PFSS and ATS., Level of Evidence: Level II, prospective cohort study., Competing Interests: Declaration of Conflicting Interests The authors received no financial support for the research, authorship, and/or publication of this article. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2023 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Background: Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCa during androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration., Methods: We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48)., Results: The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48., Conclusions: pcPrF from PCa specimens increase the expression of aberrant AR-V7 in PCa cells. IL-8 may be a target for preventing the expression of aberrant AR-Vs in PCa., (© 2022 Wiley Periodicals LLC.)

Introduction: We aimed to examine the relationship between D'Amico intermediate-risk and pathological grade group 1 (pGG1) after robot-assisted radical prostatectomy (RARP)., Patients and Methods: In this retrospective multicenter cohort study, D'Amico intermediate-risk prostate cancer patients who did not receive neoadjuvant therapy, and underwent RARP at 10 institutions in Japan were examined for preoperative factors associated with pGG1., Results: In total, we enrolled 1161 D'Amico intermediate-risk prostate cancer patients. The pGG1 and pGG ≥2 groups comprised 73 (6.3%), and 1088 (93.7%) cases, respectively. Biochemical recurrence-free survival (BCRFS) of the pGG1 group was equivalent to that of the D'Amico low-risk patients. Among the 3 D'Amico intermediate-risk factors (IRF), the pGG1-rate was 24% with prostate-specific antigen (PSA) of 10 to 20 ng/mL alone, and 30% with cT2b alone. Both groups had significantly higher pGG1-rates than other groups. Down-grading from biopsy GG ≥2 to pGG1 was relatively rare (3.9%). Patients with pGG1 were further stratified by prostate volume (PV) (cutoff, 40 cc) among patients with one IRF and PSA of 10 to 20 ng/mL. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV >40 cc had a relatively good BCRFS similar to that of the D'Amico low-risk group., Conclusion: Among intermediate-risk prostate cancer patients, those with pGG1 have a good prognosis. Downgrading from biopsy GG ≥2 is rare, and definitive treatment may be recommended for patients with biopsy GG ≥2. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV >40 cc who are eligible for RARP may be candidates for active surveillance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis., Methods: This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients' medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment., Results: Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months., Conclusions: The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy., (© The Author(s) 2022. Published by Oxford University Press.)

Whether a droplet slides or not on inclined solid surface is mainly influenced by a balance between the adhesion force at contact area and the gravitational force exerted on the droplet. Especially as the adhesion force is a key parameter for the determination of the sliding behavior of droplets. The adhesion force is mainly estimated by experimental observation for the sliding motion of the droplet. However, at present it is unknown whether the adhesion force is a constant value regardless of the droplet size or not. In the present study, focused on the onset for sliding of water-ethanol binary mixture droplets on inclined solid surface, experimental investigation on the sliding droplets is performed by considering the droplet volumes ranging from 7 to 600 μL in order to understand the effect of the size of the droplet on the adhesive property. The results are discussed using the existing analytical models. From the results, it is found that the adhesion force increases in the case of large droplet volume, while the force reaches constant value in the case of small droplet volume. This difference is related to the degree of the droplet shape deformation, which leads to a change in the contact angle. Finally, a simple empirical model for the adhesion force including the size effect is proposed.

Purpose: To retrospectively evaluate the treatment outcomes of thermal ablation for renal metastatic tumors., Materials and Methods: Thirteen consecutive patients with small renal metastatic tumors (≤3 cm), who underwent thermal ablation between 2009 and 2020, were included in this study. Eight patients had extra-renal tumors during renal ablation. The primary tumors were adenoid cystic carcinoma in four patients, lung cancer in three, hemangiopericytoma in three, leiomyosarcoma in two, and thyroid cancer in one. The therapeutic effects, safety, survival rate, prognostic factor, and renal function were evaluated., Results: We performed 18 ablation sessions (cryoablation, n = 13; radiofrequency ablation, n = 5) on 19 renal metastases with a mean diameter of 1.7 cm, which resulted in a primary technique efficacy rate of 100% without procedure-related deaths or major complications. Renal function significantly declined 6 months after ablation ( P = 0.0039). During the mean follow-up period of 31.2 ± 22.4 months (range, 2.7-71.4 months), one patient had local tumor progression at 11.9 months following radiofrequency ablation. The overall survival rates at 1 and 3 years after ablation were 76.9% (95% confidence interval [CI], 54.0%-99.8%) and 59.3% (95% CI, 31.3%-87.3%), respectively. Tumor size ≥ 2 cm ( P = 0.02) and metastasis from non-small cell lung cancer ( P = 0.001) were significant worse prognostic factors in univariate analysis, and metastasis from non-small cell lung cancer ( P = 0.01) was significant in multivariate analysis., Conclusions: Percutaneous thermal ablation for small renal metastases is safe and feasible and can control local tumors., Competing Interests: One of the authors (H.S.) has received research grants from DAIICHI SANKYO COMPANY, LIMITED, Fuji Pharma Co., Ltd., FUJIFILM RI Pharma Co., Ltd., and Eisai Co., Ltd. All other authors declare that there are no relevant conflicts of interest. This study was not supported by any funding., (© 2022 Japanese Society of Interventional Radiology.)

In ruminants, uterine glands play key roles in the establishment of pregnancy by secreting various factors into the uterine lumen. Although a three-dimensional (3D) culture system has been used for investigating cellular functions in vitro, the detailed functions of uterine gland have not been fully elucidated. In this study, we examined the benefits of 3D culture system to examine the innate functions of bovine uterine glands. Isolated bovine uterine glands were cultured on Matrigel (2D) or in Matrigel (3D), respectively, and the mRNA levels of secreted proteins (SERPINA14, MEP1B, APOA1, ARSA, CTGF, and SPP1) were measured in isolated and cultured uterine glands. The protein expression of estrogen receptor β (ERβ) and progesterone receptor (PR) and the establishment of apico-basal polarity were examined. In isolated uterine glands, the mRNA levels of secreted proteins changed during the estrous cycle. Although uterine glands cultured in both 2D and 3D expressed ERβ and PR, progesterone did not affect SERPINA14 mRNA expression. The expression of APOA1 mRNA in 2D cultured uterine glands did not respond to estrogen and progesterone. Additionally, the mRNA levels of secreted proteins in the 3D culture system were significantly higher than those in the 2D culture system, which might be attributed to the different cellular morphology between them. The locations of ZO-1 and β-catenin in 2D cultured uterine glands were disordered compared with 3D cultured uterine glands. These results showed that the hormonal responsiveness of secreted factor expression and cellular morphology were different between 2D and 3D cultured bovine uterine glands.

Objective: This study aimed to evaluate the reliability of the diastasis measurements between the medial cuneiform and the second metatarsal on weightbearing radiography., Materials and Methods: We retrospectively examined 18 patients who underwent open surgery for subtle Lisfranc injuries. Preoperative weightbearing radiography of the affected and unaffected feet was evaluated in all patients. The diastasis between the medial cuneiform and the second metatarsal was measured in both feet using the following four methods: diastasis between parallel lines, distal point diastasis, middle point diastasis, and proximal point diastasis. Intraclass correlation coefficients with consistency of agreement were calculated to evaluate inter- and intraobserver reliability., Results: The intra- and interobserver reliabilities of all four methods were good. Intraclass correlation coefficients for intraobserver reliability ranged from 0.87 to 0.93. Those for interobserver reliability ranged from 0.81 to 0.91., Conclusions: The reliabilities of the diastasis measurement methods between the medial cuneiform and the second metatarsal on weightbearing radiography were good. Measuring the diastasis between the medial cuneiform and the second metatarsal on weightbearing radiography is useful in evaluating subtle injuries when uniform measurement methods are used., (© 2021. ISS.)

Background: Recurrence of hallux valgus deformity is a complication following surgical treatment of hallux valgus. This study was performed to identify risk factors for recurrence of hallux valgus deformity after minimally invasive distal linear metatarsal osteotomy (DLMO)., Methods: Sixty-seven patients (100 feet) with mild to severe hallux valgus who underwent DLMO from 2007 to 2018 were retrospectively investigated. Their average age at the time of surgery was 54 years (range, 18-88 years). The average follow-up duration was 46 months. The feet were divided into two groups: with and without recurrence. A multivariate analysis was performed to identify the risk factors for recurrence of deformity based on preoperative and 3-month postoperative radiographic parameters., Results: Recurrence of deformity was found in 18 (18%) of the 100 feet at the final follow-up. The preoperative hallux valgus angle and 3-month postoperative hallux valgus angle, intermetatarsal angle, round sign positivity, and sesamoid position grade were significantly greater in the recurrence group than in the non-recurrence group. The logistic regression analysis revealed that a 3-month postoperative hallux valgus angle of ≥13.5°, positive round sign, and grade ≥2 sesamoid position were significantly associated with recurrence of deformity., Conclusions: The present findings can help to identify patients at higher risk of recurrence of hallux valgus deformity after DLMO and to modify their surgical procedures., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this manuscript., (Copyright © 2021. Published by Elsevier B.V.)

The present study was performed to investigate the morphological characteristics of the calcaneofibular ligament (CFL) and evaluate its relationship to the anterior talofibular ligament (ATFL) in patients with lateral ankle ligament injury using 3-dimensional magnetic resonance imaging (3D-MRI). This retrospective study involved 35 patients with lateral ankle ligament injury and 24 patients without a history of ankle trauma and a bone abnormality as controls. Reconstructed 3D-MRI was used to classify the form of the CFL as curved, wavy, or straight. The presence/absence of continuity between the fibula and CFL was evaluated in the 35 patients with injury, who were divided into 2 groups (continuity and discontinuity groups). The number of fascicles in the ATFL and the continuity between the distal end of the fibula and the proximal end of the ATFL were then evaluated. Among the patients with injury, 54.3% had the curve type of CFL, 34.3% had the wave type, and 11.4% had the straight type. In the control group, 62.5% had the curve type, 37.5% had the wave type, and none had the straight type. Continuity between the fibula and CFL was seen in 88.6%, and discontinuity was seen in 11.4%. Additionally, 85.7% had double fascicles in the ATFL. Inferior fascicle discontinuity between the ATFL and fibula was found in 13.3% with a double-fascicle ATFL; in all of these patients, the form of the CFL was straight and exhibited inferior fascicle discontinuity. The straight form of CFL could be a 3D-MRI sign in the diagnosis of CFL and ATFL inferior fascicle injury., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To clarify the utility of microballoon catheter in renal arterial ethanol embolization of renal angiomyolipoma (AML)., Material and Methods: A total of 20 patients (15 women, 5 men) with median age of 45 years (39-60 years) underwent embolization to treat 22 AMLs. A mixture of ethanol and iodized oil was injected into the feeding arteries of 13 tumors using balloon occlusion (the balloon embolization group) with a microballoon catheter and 9 tumors without using balloon occlusion (the non-balloon embolization group). Changes in the maximum tumor diameter, tumor volume, and adverse events were evaluated., Result: The median baseline maximum tumor diameters and volumes were 6.3 cm and 61.4 cm 3 in the balloon embolization group, and 4.6 cm and 40.1 cm 3 in the non-balloon embolization group, respectively. Tumor enhancement disappeared on postembolization angiography in all cases. All tumors shrunk after embolization. There were no statistically significant differences in the percent decrease in the maximum tumor diameter and volume at 10-12 month between balloon occlusion group (31.5% and 67.9%) and control group (34.8% and 62.6%). Fever was significantly more frequent when balloon occlusion was used: 38% vs. 0% ( p = 0.03). No major complication was observed in either patient group., Conclusions: Balloon occlusion may not affect tumor shrinkage when embolizing AMLs with a mixture of ethanol and lipiodol., Competing Interests: None, (© 2022 Japanese Society of Interventional Radiology.)

We previously reported that dopamine (DA) attenuated lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines through the formation of DA quinone (DAQ) in murine microglial cell line BV-2 and primary murine microglial cells. To reveal whether DA inhibits the expression of proinflammatory cytokines of microglial cells through the formation of DAQ in the central nervous system (CNS), in this study, we examined the effect of DAQ on LPS-induced mRNA expression of proinflammatory cytokines in C57BL/6 mouse brain under two experimental conditions: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration and l-dopa/carbidopa administration. Acute MPTP administration reduced the number of tyrosine hydroxylase-positive cells in the substantia nigra, and decreased the level of quinoprotein, an indicator of DAQ formation, in the striatum. Real-time RT-PCR analysis revealed that intraperitoneal administration of LPS increased the mRNA levels of proinflammatory cytokines, including tumor-necrosis factor-α and interleukin-1β, in the striatum. These increases were enhanced in MPTP-treated mice. On the other hand, l-dopa/carbidopa administration increased the level of quinoprotein, attenuated the LPS-induced mRNA expression of proinflammatory cytokines, and reduced the LPS-induced increase in the number of microglial cells in the striatum. These results suggest that DA attenuate the expression of proinflammatory cytokines in microglia through the formation of DAQ in the CNS., (Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Here, we searched for microRNAs (miRNAs) in silico that could interact with SLC11A2 mRNA, a solute carrier (SLC) iron-ion transporter, and investigated their effects on SLC11A2 gene expression using the cultured human colon carcinoma cell line, Caco-2. In silico analysis using the miRWalk2.0 database revealed that several types of miRNAs interact with the human SLC11A2 gene; we focused on three miRNAs, miR-149-5p, miR-362-5p, and miR-539-5p as candidates in this study. We first revealed that the three miRNAs interact with the SLC11A2 3'-untranslated region (3'-UTR) using a luciferase assay in a Caco-2 cell line. We then examined whether the expression of each miRNA affected the expression of SLC11A2 mRNAs and their transcribed transporter proteins. We found transiently expressed miRNAs significantly reduced the reporter activity of the SLC11A2 3'-UTR site in Caco-2 cells by significantly decreasing the SLC11A2 gene and protein expression in the miRNA-transfected Caco-2 cells. Subsequently, we investigated the effects of these miRNAs on SLC11A2's iron-ion transporting activity by measuring iron-ion concentration in Caco-2 cells. Administration of ammonium iron (II) sulfate hexahydrate to Caco-2 cells significantly increased the intracellular iron-ion concentration. However, in iron-ion-pretreated cells, overexpression of each of the three miRNAs resulted in decreased intracellular iron-ion concentration. This indicated that overexpressed miRNAs inhibited iron-ion influx into Caco-2 cells by attenuating SLC11A2 transporting activity. Using in silico analysis, we predicted that three studied miRNAs could bind to the iron-ion influx transporter SLC11A2 and revealed that they regulate SLC11A2 gene expression and iron-ion transporting function in an in vitro system.

Background/aim: To evaluate the effectiveness and safety of nivolumab plus ipilimumab for untreated metastatic renal cell carcinoma in real-world clinical practice in Japan based on 1-year follow-up results., Patients and Methods: This multicentre, retrospective study analysed 45 metastatic renal cell carcinoma patients who received nivolumab plus ipilimumab between August 2018 and January 2019 in Japan. Data were extracted from patients' medical records. Subgroup analyses were performed based on baseline demographic data and treatment history., Results: The objective response rate was 42.5% (complete response rate: 10.0%). The 12-month overall survival rate was 81.4% and the progression-free survival rate was 56.1%. Thirty-five patients (77.8%) showed any grade treatment-related adverse events and 17 (37.8%) showed grade ≥3 treatment-related adverse events, with no significant difference in safety between subgroups., Conclusion: The effectiveness and safety of nivolumab plus ipilimumab in real-world clinical practice with 1-year follow-up were comparable with those of the CheckMate 214 trial., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of "frailty" has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm 2 ) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.