Fatal convexity and interhemispheric acute subdural hematoma from a falx meningioma: A case report.

Background: Hemorrhagic meningiomas are rare. We report a rare case of nontraumatic convexity and interhemispheric acute subdural hematoma (ASDH) caused by a falx meningioma. Case Description: An 84-year-old woman with a history of atrial fibrillation and hypertension who was taking warfarin presented to our emergency department with a sudden disorder of consciousness. The patient had no traumatic events associated with her symptoms. Computed tomography (CT) revealed right convexity and interhemispheric ASDH, mass lesions in the left frontal lobes, and brain herniation. Contrast-enhanced CT revealed vascular structures within the mass lesion. CT angiography (CTA) revealed no aneurysm or arteriovenous malformation, and the venous phase revealed occlusion in the anterior portion of the superior sagittal sinus. The patient had her right convexity and interhemispheric ASDH removed endoscopically. A mass lesion located on the falx, which was easily bleeding, soft, and suctionable, was immediately detected. Histopathological examination revealed fibrous meningioma, a benign meningioma of the World Health Organization grade 1. Despite undergoing aggressive treatment, the patient's general condition deteriorated. Conclusion: Hemorrhagic meningiomas can easily be missed with plain CT, and the enhancement effect of CTA and tumor shadow on digital subtraction angiography may not be observed during the acute phase. Surgery for nontraumatic ASDH should be performed considering the possibility that a meningioma causes it.

Usefulness of non-slip element percutaneous transluminal angioplasty scoring balloons in treating severe calcified lesions of the carotid artery for carotid artery stenting: A case report.

Background: Treatment of calcified lesions with conventional angioplasty balloons can be difficult due to insufficient lumen expansion, high dissection rates, and repeated revascularization. We report a case in which a scoring balloon was used in lesions resistant to angioplasty with a semi-compliant balloon. Case Description: A 72-year-old man presented with severe stenosis and a highly calcified lesion in the right cervical internal carotid artery. Right carotid artery stenting (CAS) was planned to prevent future ischemic stroke events. Conventional semi-compliant balloon angioplasty was unsuccessful. Three inflations of a non-slip element (NSE) percutaneous transluminal angioplasty (PTA) scoring balloon (Nipro, Osaka, Japan) successfully achieved CAS without complications. Conclusion: This is the first report to describe the use of this scoring balloon in de novo carotid artery disease. NSE PTA scoring balloon catheters can be a useful option for refractory, highly calcified stenosis.

Early diagnosis of thoracic spinal dural arteriovenous fistula using lumbar magnetic resonance imaging: A case report.

In middle-aged and older men, clinicians often suspect lumbar spine disease when gait is impaired with intermittent claudication, but spinal dural arteriovenous fistula (SDAVF) may be the etiology. An understanding of the key magnetic resonance imaging findings of SDAVF is necessary for early diagnosis, appropriate treatment, and minimization of complications.

Determining zebrafish dorsal organizer size by a negative feedback loop between canonical/non-canonical Wnts and Tlr4/NFκB.

In vertebrate embryos, the canonical Wnt ligand primes the formation of dorsal organizers that govern dorsal-ventral patterns by secreting BMP antagonists. In contrast, in Drosophila embryos, Toll-like receptor (Tlr)-mediated NFκB activation initiates dorsal-ventral patterning, wherein Wnt-mediated negative feedback regulation of Tlr/NFκB generates a BMP antagonist-secreting signalling centre to control the dorsal-ventral pattern. Although both Wnt and BMP antagonist are conserved among species, the involvement of Tlr/NFκB and feedback regulation in vertebrate organizer formation remains unclear. By imaging and genetic modification, we reveal that a negative feedback loop between canonical and non-canonical Wnts and Tlr4/NFκB determines the size of zebrafish organizer, and that Tlr/NFκB and Wnts switch initial cue and feedback mediator roles between Drosophila and zebrafish. Here, we show that canonical Wnt signalling stimulates the expression of the non-canonical Wnt5b ligand, activating the Tlr4 receptor to stimulate NFκB-mediated transcription of the Wnt antagonist frzb, restricting Wnt-dependent dorsal organizer formation.

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment.

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

Efficacy and Safety of First-Line Cytokines versus Sunitinib and Second-Line Axitinib for Patients with Metastatic Renal Cell Carcinoma (ESCAPE Study): A Phase III, Randomized, Sequential Open-Label Study.

BACKGROUND: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. METHODS: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. RESULTS: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7-46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3-26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121-1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418-6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. CONCLUSIONS: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522.

Quality of life in patients who underwent robot-assisted radical prostatectomy compared with those who underwent low-dose-rate brachytherapy.

BACKGROUND: To compare the quality of life (QOL) in patients who underwent robot-assisted radical prostatectomy (RARP) or low-dose-rate brachytherapy (LDR-BT) for prostate cancer. METHODS: We enrolled patients who underwent LDR-BT (LDR-BT alone [n = 540] or LDR-BT plus external beam radiation therapy [n = 428]) and RARP (n = 142). QOL was evaluated using the International Prostate Symptom Score, Expanded Prostate Cancer Index Composite (EPIC), Sexual Health Inventory for Men (SHIM), and 8-item Short Form (SF-8) health survey. The two groups were compared using propensity score matching analysis. RESULTS: At 24 months after treatment, the number of patients with worsened urinary QOL in the urinary domain of EPIC compared with baseline was 78/111 (70%) and 63/137 (46%) in the RARP and LDR-BT groups, respectively (p < 0.001). In the urinary incontinence and function domain, this number was higher in the RARP group versus the LDR-BT group. However, in the urinary irritative/obstructive domain, the number of patients with improved urinary QOL at 24 months compared with baseline was 18/111 (16%) and 9/137 (7%), respectively (p = 0.01). Regarding the SHIM score, sexual domain of EPIC, and mental component summary of SF-8, there were more number of patients with worsened QOL in the RARP group than in the LDR-BT group. In the EPIC bowel domain, the number of patients with worsened QOL was lower in the RARP group versus the LDR-BT group. CONCLUSION: The differences in QOL observed between patients treated with RARP and LDR-BT could assist in treatment selection for prostate cancer.

Diffuse alveolar hemorrhage and acute eosinophilic pneumonia: A rare form of amiodarone pulmonary toxicity diagnosed by bronchoalveolar lavage.

A 56-year-old man presented with fever, cough, and bloody sputum. He had undergone mitral valve replacement with mechanical prosthesis 14 months prior for mitral valve disease. Subsequently, the patient was taking warfarin and amiodarone. Chest imaging revealed dense, infiltrative shadows, and blood tests showed prolonged prothrombin time and eosinophilia. Warfarin was withdrawn, and antibiotics were started, but bloody sputum and respiratory failure persisted. Considering that eosinophilia was observed after the administration of amiodarone, the drug was discontinued, and bronchoalveolar lavage was performed. Cytology showed foam cells, eosinophils, and hemosiderin-laden macrophages; amiodarone-induced diffuse alveolar hemorrhage (DAH) and acute eosinophilic pneumonia (AEP) were diagnosed, and the patient was treated with corticosteroids. This report describes the first documented case of amiodarone-induced DAH and AEP. When a patient taking amiodarone presents with antibiotic-refractory pneumonia with bloody sputum and eosinophilia, amiodarone-induced DAH and AEP should be considered. Learning objective: We report the first case of amiodarone-induced diffuse alveolar hemorrhage (DAH) and acute eosinophilic pneumonia (AEP) diagnosed by foam cells, eosinophils, and hemosiderin-laden macrophages on bronchoalveolar lavage cytology. When a patient taking amiodarone presents with antibiotic-refractory pneumonia with bloody sputum and eosinophilia, amiodarone-induced DAH and AEP should be considered.

Successful Diagnosis by Video-Assisted Thoracoscopic Surgical Lung Biopsy in a Case of Progressive Primary Pulmonary Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: A Case Report.

Malignant pulmonary lymphoma is very rare and the majority of which are B-cell lymphomas. Since primary pulmonary extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is difficult to diagnose and associated with poor prognosis and aggressive course, some cases are diagnosed at the postmortem autopsy. We report a case of a 53-year-old man with primary pulmonary ENKL diagnosed by video-assisted thoracoscopic surgery (VATS) lung biopsy. This case explains the importance of VATS lung biopsy and in-depth evaluation, including flow cytometry, chromosome, genetic, and immunostaining tests, when primary pulmonary malignant lymphoma is suspected.

Lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: Japanese patients from the CLEAR study.

BACKGROUND: The phase 3 CLEAR study demonstrated statistically significantly improved efficacy with lenvatinib plus pembrolizumab versus sunitinib, including progression-free survival and overall survival, in patients with previously untreated advanced renal cell carcinoma. This subset analysis investigated efficacy and safety in Japanese patients randomized to lenvatinib plus pembrolizumab or sunitinib in the CLEAR study. METHODS: Progression-free survival, overall survival, tumor response, and safety were assessed in Japanese patients with previously untreated advanced renal cell carcinoma randomized to receive lenvatinib plus pembrolizumab (n = 42) or sunitinib (n = 31). Efficacy outcomes were analyzed by independent imaging review per Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 22.1 vs. 10.9 months; hazard ratio, 0.39; 95% CI, 0.20-0.74). Median overall survival was not estimable in the lenvatinib plus pembrolizumab arm and 30.6 months in the sunitinib arm (HR, 1.20; 95% CI, 0.39-3.66). Overall survival adjusted for the imbalance of Memorial Sloan-Kettering Cancer Center prognostic risk group favored lenvatinib plus pembrolizumab (hazard ratio, 0.67; 95% CI, 0.18-2.39). Objective response rate (69.0% vs. 45.2%; odds ratio, 2.71; 95% CI, 1.03-7.10) was higher and median duration of response (20.3 vs. 9.1 months) was longer with lenvatinib plus pembrolizumab versus sunitinib. Grade ≥ 3 treatment-emergent adverse events occurred in 95.2% versus 87.1% of patients in the lenvatinib plus pembrolizumab versus sunitinib arms. CONCLUSIONS: These findings support lenvatinib plus pembrolizumab as a potential first-line treatment for Japanese patients with advanced renal cell carcinoma.

Prognostic value of immune phenotype and PD-L1 status in recurrent or metastatic renal cell carcinoma: an exploratory analysis of the ARCHERY study.

Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis.

Deep Learning Models to Predict Fatal Pneumonia Using Chest X-Ray Images.

Background and Aims: Chest X-ray (CXR) is indispensable to the assessment of severity, diagnosis, and management of pneumonia. Deep learning is an artificial intelligence (AI) technology that has been applied to the interpretation of medical images. This study investigated the feasibility of classifying fatal pneumonia based on CXR images using deep learning models on publicly available platforms. Methods: CXR images of patients with pneumonia at diagnosis were labeled as fatal or nonfatal based on medical records. We applied CXR images from 1031 patients with nonfatal pneumonia and 243 patients with fatal pneumonia for training and self-evaluation of the deep learning models. All labeled CXR images were randomly allocated to the training, validation, and test datasets of deep learning models. Data augmentation techniques were not used in this study. We created two deep learning models using two publicly available platforms. Results: The first model showed an area under the precision-recall curve of 0.929 with a sensitivity of 50.0% and a specificity of 92.4% for classifying fatal pneumonia. We evaluated the performance of our deep learning models using sensitivity, specificity, PPV, negative predictive value (NPV), accuracy, and F1 score. Using the external validation test dataset of 100 CXR images, the sensitivity, specificity, accuracy, and F1 score were 68.0%, 86.0%, 77.0%, and 74.7%, respectively. In the original dataset, the performance of the second model showed a sensitivity, specificity, and accuracy of 39.6%, 92.8%, and 82.7%, respectively, while external validation showed values of 38.0%, 92.0%, and 65.0%, respectively. The F1 score was 52.1%. These results were comparable to those obtained by respiratory physicians and residents. Conclusions: The deep learning models yielded good accuracy in classifying fatal pneumonia. By further improving the performance, AI could assist physicians in the severity assessment of patients with pneumonia.

[The Relationship between Sarcopenia and Survival after Cabazitaxel Treatment for Castration-Resistant Prostate Cancer].

Sarcopenia is a known predictor of overall survival in several diseases. We investigated the relationship between sarcopenia and outcome of treatment with cabazitaxel (CBZ) for castration-resistant prostate cancer (CRPC) by a retrospective analysis of 37 patients, who were given cabazitaxel at our hospital, from December 2014 to November 2020. The skeletal muscle mass was evaluated using the Psoas Muscle Mass Index (PMI: psoas major muscle area at the level of the third lumber vertebra (cm²)/height x height (m²)) through computed tomography images. The severe sarcopenia group (PMI＜4.96) showed lower levels of serum albumin, in comparison with the non-severe sarcopenia group (PMI≥4.96). Multivariate analysis identified PMI (odds ratio＝3.7; P＝0.023) as an independent factor associated with prostate specific antigen response to CBZ therapy. However, there was no significant difference in the overall survival between the severe and the non-severe sarcopenia groups (P＝0.1). Skeletal muscle mass might be closely correlated to the therapeutic response to CBZ, but not to the prognosis of patients with CRPC. Nutritional rehabilitation and exercises targeting sarcopenia for patients with prostate cancer should be considered.

Trends in primary treatment for localized prostate cancer according to the availability of treatment modalities and the impact of introducing robotic surgery.

OBJECTIVES: We aimed to investigate the effect of available treatment modalities on primary treatment selection in patients with localized prostate cancer and that of introducing robotic surgery. METHODS: We retrospectively studied 12 061 patients diagnosed with localized prostate cancer between 2004 and 2018 from 21 institutions. These institutions were divided into five groups according to the availability of surgery and radiotherapy. Differences in primary treatment selection between the institutions were investigated, and the predictive factors involved in the selection were explored. RESULTS: Surgery, radiotherapy, androgen deprivation therapy, and active surveillance/watchful waiting were selected as primary treatment in 4115, 3621, 3188, and 821 patients, respectively, while the remaining 316 patients selected other modalities. The number of patients, particularly young patients, was much higher in institutions with both surgery and radiotherapy. With the introduction of robotic surgery, open radical prostatectomy has decreased, and robotic surgery made up approximately 70% of all prostatectomies. Institutions with both surgery and radiotherapy tended to treat patients with very low or low risk by surgery or radiotherapy, while institutions without surgery and radiotherapy tended to select active surveillance or watchful waiting. Multivariate analysis revealed that primary treatment selection for prostate cancer was affected not only by clinical factors, but also by the available modalities in each institution. CONCLUSIONS: Differences in available treatment modalities affect the selection of primary treatment for localized prostate cancer. Introduction of robotic surgery also has a strong influence on the number of patients in each institution.

5-Aminolevulinic acid overcomes hypoxia-induced radiation resistance by enhancing mitochondrial reactive oxygen species production in prostate cancer cells.

BACKGROUND: The naturally occurring amino acid 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) biosynthesised in the mitochondria. When accumulated PpIX is excited by light (wavelength of 625-635 nm), reactive oxygen species (ROS) are generated. Here, we investigated whether 5-ALA may increase the sensitisation of prostate cancer (PCA) cells to radiotherapy through the generation of ROS via its metabolite, PpIX. METHODS: Effect of 5-ALA on PC-3 and DU-145 PCA cell lines treated with ionising radiation (IR) was examined in vitro and in vivo with assessment by clonogenic assay, mitochondrial function and ROS production under normoxia or hypoxia condition. RESULTS: 5-ALA enhanced intra-mitochondrial ROS production immediately after exposure to IR and decreased mitochondrial membrane potential via increase of intra-cellular PpIX. IR with 5-ALA induced mitochondrial dysfunction and increased ATP production, switching energy metabolism to the quiescence. Under hypoxic condition, ROS burst and mitochondrial dysfunction were induced by IR with 5-ALA resulting reducing cancer stemness and radiation resistance. CONCLUSION: These results suggest that combined therapy with 5-ALA and radiation therapy is a novel strategy to improve the anti-cancer effects of radiation therapy for PCA.

Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer.

PURPOSE: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG). METHODS: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively. RESULTS: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration. CONCLUSIONS: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

A prospective, single-arm trial of fluorescent ureteroscopy-assisted thulium-holmium:YAG dual laser ablation for upper urinary tract cancer: Study protocol of the FLUAM trial.

Background: Latest guidelines recommend kidney-sparing management as the primary treatment option for selected patients with upper urinary tract urothelial carcinoma (UTUC). One of the biggest issues of ureteroscopic laser ablation (ULA) is a high rate of surgical site recurrence, which is largely attributed to residual lesions at the initial ULA. Another clinical issue is a significant lack of non-invasive reliable detection tools of urinary recurrent tumors in this treatment setting. Methods: The FLUAM trial is a prospective, single-center, single-arm pilot trial to investigate the efficacy of 5-aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD)-assisted ULA for localized UTUC and the usefulness of the UroVysion® assay (multiprobe fluorescence in situ hybridization) as a monitoring test after the kidney-sparing treatment. After the screening and registration, a total of 20 patients with localized UTUC will undergo the initial ALA-PDD-assisted ULA followed by the second look ALA-PDD-assisted ureteroscopic examination. The primary endpoint is progression-free survival. Secondary endpoints include patient reported outcomes, diagnostic accuracy of UroVysion assay to detect tumor recurrence, adverse events, and safety of the intervention. Conclusion: The goal of this trial is to determine the potential benefit of ALA-PDD assistance in patients who undergo the ULA. The evidence of this novel technique is still limited. The results are expected to change the standard of care and lead to better management of localized UTUC. Trial registration: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 23 June 2021. The reference number is jRCTs051210042, nara0023 (Certified Review Board of Nara Medical University).

Significant Improvement of Prognosis After the Advent of Immune Checkpoint Inhibitors in Patients with Advanced, Unresectable, or Metastatic Urothelial Carcinoma: A Propensity Score Matching and Inverse Probability of Treatment Weighting Analysis on Real-World Data.

PURPOSE: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment. PATIENTS AND METHODS: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model. RESULTS: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age <70 years), those who received radical surgery, and those without visceral metastasis. CONCLUSION: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.

Mirabegron Reduces Urinary Frequency and Improves Overactive Bladder Symptoms at 3 Months After 125I-brachytherapy for Prostate Cancer: An Open-Labeled, Randomized, Non-Placebo-Controlled Study.

OBJECTIVE: To evaluate the additional effects of mirabegron to alpha-1 adrenergic antagonist on lower urinary tract symptoms of patients who underwent 125I-brachytherapy for prostate cancer. PATIENTS AND METHODS: Patients who underwent 125I-brachytherapy for prostate cancer (cT1-cT3aN0M0) in a single institute between September 2016 and October 2018 were enrolled in the randomized, non-placebo, open-labeled, paralleled study. Patients were randomly distributed (1:1) to combination group (tamsulosin (0.2 mg/day) plus mirabegron (50 mg/day)) or tamsulosin-alone group after 125I -brachytherapy by envelope method. The primary endpoint was the change from baseline in mean voided volume per micturition 3 months after 125I brachytherapy. The secondary endpoints included the changes from baseline of International Prostate Symptom Score, Overactive Bladder Symptom Score, and Expanded Prostate Cancer Index Composite scores and 24 hours urinary frequency after 3 months after 125I brachytherapy. RESULTS: The mean changes in volume voided per micturition in the combination (n = 108) and tamsulosin-alone (n = 110) groups were -62.5 (standard deviation, ±53.8) and -68.0 (standard deviation, ±52.7), respectively (P = .17). The change in Overactive Bladder Symptom Score in combination group (P = .02) was more moderate than in tamsulosin-alone group; and 24 hour urinary frequency in combination group was lower (P = .03) than in tamsulosin-alone group. Retention rates within 3 months after 125I-brachytherapy in the mirabegron and tamsulosin-alone groups were 7.3% (9/122) and 6.0% (7/118), respectively (P = .80). CONCLUSION: Tamsulosin and mirabegron combination therapy after 125I-brachytherapy did not improve voided volume per micturition compared to tamsulosin-only treatment. However, it could improve frequent urination and overactive bladder symptoms.

Erectile dysfunction and sexual quality of life in patients who underwent low-dose-rate brachytherapy alone for prostate cancer.

This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low-dose-rate brachytherapy (LDR-BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR-BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post-implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR-BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR-BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL.