Clinical comparison and genetic analysis in pheochromocytoma with primary aldosteronism.

Pheochromocytoma is a rare form of adrenal hypertension. This study aimed to investigate the clinical characteristics and associated genetic mutations in patients with pheochromocytoma and primary aldosteronism. We retrospectively analyzed data from 23 patients with pheochromocytoma diagnosed and treated between 2011 and 2022.

Genomic profiling and clinical utility of circulating tumor DNA in metastatic prostate cancer: SCRUM-Japan MONSTAR SCREEN project.

Background: Circulating tumor DNA (ctDNA) testing has emerged as a novel tool for cancer precision medicine. This study investigated the genomic profiling and clinical utility of ctDNA in metastatic prostate cancer.

Methods: This is a nation-wide prospective observational study.

Prediction of undetectable circulating tumor DNA by comprehensive genomic profiling assay in metastatic prostate cancer: the SCRUM-Japan MONSTAR SCREEN project.

Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer.

Patients And Methods: Patients treated with systemic treatment for metastatic prostate cancer were included.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

Objectives: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC.

Methods: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020.

Differences in oncological benefits from second transurethral resection between white-light initial surgery and photodynamic diagnosis-guided initial surgery for primary high-risk non-muscle invasive bladder cancer.

Objectives: The aim of this study was to compare clinical outcomes between patients receiving second TUR after initial white-light transurethral resection of bladder tumor (WL-TURBT) and initial photodynamic diagnosis (PDD)-assisted TURBT.

Methods: A total of 1007 patients were divided into four groups based on the treatment pattern: WL-TURBT with second TUR (161 patients, WL-second group) or without second TUR (540 patients, WL-alone group) and PDD-TURBT with second TUR (112 patients, PDD-second group) or without second TUR (194 patients, PDD-alone group). Oncologic outcomes (bladder cancer recurrence, progression, urothelial cancer-specific mortality) and rates of residual tumor and risk stratification of non-muscle-invasive bladder cancer (NMIBC) after second TUR were evaluated.

Flare phenomenon visualized by Tc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer.

Objective: This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from Tc-methylenediphosphonate (MDP) bone scintigraphy images.

Methods: We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2 years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3 months of starting chemotherapy, followed by > 10% improvement within the next 3 months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses.

New risk stratification for adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma.

Objectives: We aim to evaluate the risk of recurrence after neoadjuvant chemotherapy followed by radical cystectomy, particularly in ypT2 disease in patients with urothelial carcinoma, because it is not clear if all eligible patients with high-risk muscle-invasive urothelial carcinoma should be treated with adjuvant nivolumab.

Materials And Methods: We analysed the radiological and clinicopathological features, including cT and ypT stages, of 197 patients who had undergone two to four cycles of cisplatin-based neoadjuvant chemotherapy and radical cystectomy without adjuvant chemotherapy. We stratified the risk of postoperative recurrence by these factors.

Pathology and gene mutations of aldosterone-producing lesions.

The human adrenal cortex secretes aldosterone and cortisol as major corticosteroids. For their production, CYP11B2 and CYP11B1 catalyze the last steps in the syntheses of aldosterone and cortisol, respectively. In our previous study, CYP11B2 was the first successfully purified from rat adrenals and human clinical samples and then was proved to be aldosterone synthase.

Impact on Japanese healthcare economics of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer: A multicenter retrospective cohort study.

Objectives: Bladder cancer, especially non-muscle invasive bladder cancer (NMIBC), is one of the most costly cancers owing to its long-term management. Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) reduces the risk of intravesical recurrence. However, its impact on healthcare economics in Japan remains unclear.

Additional oncological benefit of photodynamic diagnosis with blue light cystoscopy in transurethral resection for primary non-muscle-invasive bladder cancer: A comparative study from experienced institutes.

Objectives: The objective of this work is to evaluate the additional oncological benefit of photodynamic diagnosis (PDD) using blue-light cystoscopy in transurethral resection (TURBT) for primary non-muscle-invasive bladder cancer (NMIBC) based on the International Bladder Cancer Group (IBCG)-defined progression and the subsequent pathological pathways.

Patients And Methods: We reviewed 1578 consecutive primary NMIBC patients undergoing white-light TURBT (WL-TURBT) or PDD-TURBT during 2006-2020. One-to-one propensity score-matching was performed using multivariable logistic regression to obtain balanced groups.

IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation.

Background: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis.

Efficacy of abiraterone acetate for high-risk hormone-naïve metastatic prostate cancer: A comparison with combined androgen blockade therapy with bicalutamide and androgen deprivation therapy alone.

Background: The treatment landscape for men with metastatic hormone-naïve prostate cancer (mHNPC) has dramatically changed with the approval of next-generation anti-androgen drugs. We compared the treatment efficacy of abiraterone with that of combined androgen blockade (CAB) therapy and androgen deprivation therapy (ADT) alone in men with high-risk mHNPC.

Methods: In total, 146 Japanese men with high-risk mHNPC were retrospectively analyzed.

Predictive factors for the effectiveness of novel androgen receptor axis-targeted agents in patients with metastatic prostate cancer.

Objective: Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs.

Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study).

Origin of circulating 18-oxocortisol in the normal human adrenal.

18-Oxocortisol is the product of the metabolism of 11-deoxycortisol by the mitochondrial enzyme aldosterone synthase (CYP11B2). The traditional concept is that the CYP11B2 is exclusively expressed in zona glomerulosa cells and the 17α-hydroxylase (CYP17A1) enzyme, required to synthesize 11-deoxycortisol, is in the zona fasciculata of the human adrenal. It has been postulated that the substrate for 18-oxocortisol is either cortisol from the circulation or from zona fasciculata cells adjacent to the zona glomerulosa.

Characterization of Aldosterone-producing Cell Cluster (APCC) at Single-cell Resolution.

Context: The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that strongly express aldosterone synthase (CYP11B2) are frequently found in adult adrenals and harbor somatic mutations that are also detected in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA).

Familial Hyperaldosteronism Type 3 with a Rapidly Growing Adrenal Tumor: An In Situ Aldosterone Imaging Study.

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel . Germ line mutations of cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension.

Lower neutrophil-to-lymphocyte ratio and positive programmed cell death ligand-1 expression are favorable prognostic markers in patients treated with pembrolizumab for urothelial carcinoma.

Background: Immune checkpoint inhibitors (ICIs) are effective in some cancer patients; however, they may show no efficacy in others. Predictive biomarkers are crucial for appropriately selecting the patients who receive ICI therapy. This study aimed to clarify the predictors of disease progression in urothelial carcinoma (UC) patients treated with an ICI, pembrolizumab.

Efficacy of Androgen Receptor-targeted Drugs After Prostate Cancer Recurrence With Bone Metastases: PROSTAT-BSI Sub-analysis.

Background/aim: This study aimed to evaluate the therapeutic benefit of novel androgen receptor-targeted agents (ARTAs) in castration-resistant prostate cancer (CRPC) with bone metastases in Japan.

Patients And Methods: In followup to our prospective observational study (PROSTAT-BSI) from 2012 to 2018 on metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic CRPC (mCRPC) before docetaxel initiation, we conducted this sub-analysis to investigate the benefit of ARTAs after clinical recurrence on overall survival (OS) in the real-world clinical setting in Japan. In this study, we compared patients who were treated with ARTA with those who received only vintage hormone therapy including docetaxel after clinical recurrence.

Case Study: A Japanese patient with metastatic renal cell carcinoma who achieved long-term treatment-free survival with pembrolizumab and axitinib in the KEYNOTE-426 phase III trial of pembrolizumab and axitinib versus sunitinib.

Introduction: Our patient treated with pembrolizumab and axitinib is one of the longest survivors in Japan on KEYNOTE 426, despite adverse events, including delayed-onset hepatitis. We herein present a detailed clinical course and short discussion on the case.

Case Presentation: This was a 49-year-old male with clear cell renal cell carcinoma and lung metastases.

Oncological outcomes of dose reductions in cisplatin due to renal dysfunction for patients with metastatic urothelial carcinoma.

Objective: To investigate whether dose reductions in cisplatin due to renal dysfunction were associated with worse clinical outcomes in metastatic urothelial carcinoma (UC) patients.

Patients And Methods: One hundred and fifty one metastatic UC patients who received first-line gemcitabine plus cisplatin (GC) salvage chemotherapy without a previous history of peri-surgical chemotherapy were included in this retrospective study. Patients with endogenous creatinine clearance of 60 mL/min or more were treated with a full dose of cisplatin, while those with 45-59 and 30-44 mL/min were treated with 75% and 50% doses, respectively.