[A Case of Systemic Wild-Type Transthyretin Amyloid (ATTR) Amyloidosis Diagnosed in a Patient with Gross Hematuria].

An 85-year-old woman visited our hospital with a complaint of asymptomatic gross hematuria. Cystoscopy showed a non-papillary sessile tumor about 3 cm in size. Magnetic resonance imaging (MRI) suggested invasion of surrounding fat tissue. Thoracoabdominal contrast-enhanced computed tomography (CT) showed no tumor of the upper urinary tract or metastasis. We diagnosed the tumor as bladder cancer cT3N0M0 and performed transurethral bladder tumor resection 22 days after her first visit. No tumor was found at the time of surgery. We resected a reddened area to include a muscle layer and performed random biopsy. Hematoxylin and eosin stain showed eosinophilic tuberous tissue that stained with Congo red around blood vessels in the subepithelial stroma and the muscle layer. There was no dysplasia in the bladder epithelium. Therefore, we diagnosed the case as bladder amyloidosis. Immunostaining of the amyloid subtype revealed transthyretin amyloid (ATTR) amyloidosis. Bence-Jones protein in urine was negative, M protein was not detected in serum protein electrophoresis, and serum amyloid A was at the threshold. Scintigraphy for 99m Tc pyrophosphoric acid was positive in the myocardium. No genetic disorder was detected. We concluded that it was systemic ATTRwt amyloidosis as above. The patient did not wish to be treated for the systemic amyloidosis. Thirteen months after surgery, the patient showed no signs of recurrence in the bladder. As cardiac function is a prognostic factor in systemic amyloidosis, we need to consider the possibility of systemic amyloidosis when diagnosing bladder amyloidosis.

[Tumor Shrinkage as a Prognostic Factor of Metastatic Renal Cell Carcinoma in the Era of Molecular Targeted Therapy].

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to -20%, and 8 ≦-20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to -20%, and ≦-20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p<0. 001). These findings suggest that early TS affects overall survival in real practice. We should consider alternative therapies for patients who have not achieved tumor reduction at the initial evaluation.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

[A Case of Adrenal Ganglioneuroma that was Hard to Diagnose].

A 72-year-old man was referred to our hospital for examination of a right adrenal tumor incidentally found by computed tomography for close inspection of lumbago. The computed tomography scan and magnetic resonance imaging showed a 51×54×43 mm solid tumor in the right adrenal region. Endocrinological examinations were within normal limits. Because we could not diagnose his condition due to atypical radiographic findings preoperatively and exclude a malignant tumor, laparoscopic right adrenalectomy was performed. The tumor was histologically diagnosed as ganglioneuroma originating from the right adrenal glands.

Efficacy of cognitive behavioral therapy using self-check sheet for patients with nocturia in real-world clinical practice.

OBJECTIVES: We previously demonstrated the efficacy of cognitive behavioral therapy (CBT) using a self-check sheet for patients with nocturia in a randomized controlled study. Additionally, we investigated the efficacy of the intervention in real-world clinical practice. METHODS: Two hundred forty-three outpatients with complaint of nocturia who practiced CBT for 4 weeks using a self-check sheet were included in this trial, which took place from April 2021 to March 2022 in 20 institutions. RESULTS: Of the 243 patients, 215 who achieved 50% or more of the behavioral therapy tasks were included in the analysis. Their mean age ± SD was 77.1 ± 7.7. A significant decrease was observed in nighttime frequency at 4 weeks after CBT using self-check sheets (pre 3.3 and post 2.8, p < .001). Nighttime frequency was decreased one or more times and was defined as treatment success in 102 patients (47.4%). Pretreatment nighttime frequency in the treatment-success group was significantly higher than that of the failure group (3.5 ± 1.0 vs. 3.2 ± 1.0, p = .013). In multivariate logistic regression analysis, predictive factors of treatment success were pretreatment nocturnal frequency of four or more (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.01-3.30; p = .046) and the absence of diabetes mellitus (OR 3.08, 95% CI 1.34-7.06; p = .008). CONCLUSIONS: CBT using a self-check sheet requiring less time, less labor, less cost, and less medication is very beneficial for both patients and medical staff in real-world clinical practice.

Physical and Psychological Effects of Gender-Affirming Hormonal Treatment Using Intramuscular Testosterone Enanthate in Japanese Transgender Men.

INTRODUCTION: The evidence on gender-affirming hormonal treatment (HT) for transgender persons is still insufficient. AIM: To characterize the physical and psychological effects of HT using testosterone enanthate in transgender men, and to validate the safety of this treatment. METHODS: A total of 85 Japanese transgender men who were followed up for at least 1 year at our gender clinic from 2004 to 2017 were included in this study. All self-reported effects that they recognized and regularly acquired laboratory data were investigated after initiation of HT. MAIN OUTCOME MEASURE: HT mainly using testosterone enanthate 250 mg every 2 weeks caused the most desired physical effects to appear promptly and effectively, whereas small but not negligible numbers of undesired physical and psychological effects were also confirmed. RESULTS: The initial dose of testosterone enanthate was 250 mg for 72 (84.7%) subjects, and the injection interval was maintained every 2 weeks for 70 (82.3%). Most physical effects appeared within 6 months. A deepened voice (87.1%), cessation of menses (78.8%), acne (69.4%), and facial (52.9%)/body (37.6%) hair growth occurred within 3 months. Although recognition of psychological effects was rare, emotional instability (9.4%) and increased libido (7.1%) appeared in the relatively early phase after beginning HT. The mean values for red blood cells, hemoglobin, uric acid, and alkaline phosphatase were significantly increased for 2 year. During the observation period, there were no life-threatening adverse effects in any subjects. CONCLUSION: The present HT strategy is effective and safe for Japanese transgender men. The information from self-reported effects and objective data from blood tests can help both physicians and transgender men to understand testosterone HT. Kirisawa T, Ichihara K, Sakai Y, et al. Physical and Psychological Effects of Gender-Affirming Hormonal Treatment Using Intramuscular Testosterone Enanthate in Japanese Transgender Men. Sex Med 2021;9:100306.

A case of ureteral obstruction and sepsis induced by bladder perforation following intravesical bacillus Calmette-Guérin successfully treated with an antituberculous agent, antimicrobial chemotherapy and percutaneous urine drainage.

We report a case of ureteral obstruction and sepsis induced by bladder perforation following intravesical bacillus Calmette-Guérin (BCG) that was successfully treated non-surgically. A 56-year-old man was diagnosed with non-muscle invasive bladder cancer. He was treated with intravesical BCG instillation after transurethral resection of the bladder tumor. Just before the 6th course of intravesical BCG, the patient was diagnosed with bladder perforation and developed ureteral obstruction and sepsis associated with BCG. He was treated successfully with an antituberculous agent, antimicrobial chemotherapy and percutaneous urine drainage. Bladder perforation associated with BCG is a very rare adverse event that causes severe sepsis.

HLA-A24 ligandome analysis of colon and lung cancer cells identifies a novel cancer-testis antigen and a neoantigen that elicits specific and strong CTL responses.

This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis). The SUV39H2 peptide is immunogenic and elicits cytotoxic CD8+ T-cell (CTL) responses against cancer cells and is thus a novel cancer-testis antigen. Moreover, we found that microsatellite instability (MSI)-colon cancer cells displayed a neoepitope with an amino-acid substitution, while microsatellite stable (MSS)-colon and lung cancer cells displayed its counterpart peptide without the substitution. Structure modeling of peptide-HLA-A24 complexes predicted that the mutated residue at P8 was accessible to T-cell receptors. The neoepitope readily elicited CTL responses, which discriminated it from its wild-type counterpart, and the CTLs exhibited considerably high cytotoxicity against MSS-colon cancer cells carrying the responsible gene mutation. The specific and strong CTL lysis observed in this study fosters our understanding of immune surveillance against neoantigens.