Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab.

INTRODUCTION: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. PATIENTS AND METHODS: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan-Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. RESULTS: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan-Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. CONCLUSION: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes.

BACKGROUND: Transgender individuals undergo the gender-affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long-term safety and efficacy of GAHT. OBJECTIVES: To investigate the long-term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose. MATERIALS AND METHODS: Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low-dose group (≤ 62.5 mg/wk) to a high-dose group (> 62.5 mg/wk). RESULTS: Of 291 participants, 188 patients (64.6%) were in the low-dose group and 103 (35.4%) in the high-dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high-dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long-term, dose-dependent side effects such as polycythemia or dyslipidemia. CONCLUSION: Long-term GAHT for trans men is safe and effective. Low-dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.

Current status and future perspectives on robot-assisted kidney autotransplantation: A literature review.

This review presents the latest insights on robot-assisted kidney autotransplantation (RAKAT). RAKAT is a minimally invasive surgical procedure and represents a promising alternative to conventional laparoscopic nephrectomy followed by open kidney transplantation for the treatment of various complex urological and vascular conditions. RAKAT can be performed either extracorporeally or intracorporeally. Additionally, a single-port approach can be performed through one small incision without the need to reposition the patient. Of 86 patients undergoing RAKAT, 8 (9.3%) developed postoperative > Grade 2 Clavien-Dindo (CD) complications. Although the feasibility of RAKAT was established in 2014, the long-term efficacy and safety along with outcomes of this surgical approach are still being evaluated, and additional studies are needed. With improvements in the technology of RAKAT and as surgeons gain more experience, RAKAT should become increasingly used and further refined, thereby leading to improved surgical outcomes and improved patients' quality of life.

Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

PURPOSE: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. METHODS: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. RESULTS: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. CONCLUSION: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma.

One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed "oligo-recurrent" disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as "oligo-progression", can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.

Bladder tuberculosis with ureteral strictures after bacillus Calmette­Guérin therapy for urinary bladder cancer: A case report.

Intravesical immunotherapy using bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate- to high-risk non-muscle invasive bladder cancer. Bladder tuberculosis (TB) is a rare complication of BCG therapy. The present study describes the case of a 73-year-old man who underwent intravesical BCG therapy for urothelial carcinoma in situ of the bladder. Red patches around the resection scar were first detected 1 year and 5 months after BCG treatment; these findings gradually spread to encompass more of the bladder wall. Transurethral biopsy revealed a benign lesion, but the patient developed bilateral hydronephrosis and mild voiding dysfunction. The patient was eventually diagnosed with bladder TB by mycobacterial urine culture and TB-specific polymerase chain reaction (PCR). The patient was given multidrug therapy (isoniazid, rifampicin and ethambutol) and their bladder TB was completely cured; however, their voiding dysfunction and bilateral hydronephrosis did not fully improve. Bladder TB can occur long after intravesical BCG administration and cystoscopy findings consistent with inflammation can be the key to suspecting this condition. Acid-fast examination and PCR testing of a urine sample are necessary for early diagnosis.

Anionic ordering in Pb2Ti4O9F2 revisited by nuclear magnetic resonance and density functional theory.

A combination of 19F magic angle spinning (MAS) nuclear magnetic resonance (NMR) and density functional theory (DFT) were used to study the ordering of F atoms in Pb2Ti4O9F2. This analysis revealed that F atoms predominantly occupy two of the six available inequivalent sites in a ratio of 73 : 27. DFT-based calculations explained the preference of F occupation on these sites and quantitatively reproduced the experimental occupation ratio, independent of the choice of functional. We concluded that the Pb atom's 6s2 lone pair may play a role (∼0.1 eV per f.u.) in determining the majority and minority F occupation sites with partial density of states and crystal orbital Hamiltonian population analyses applied to the DFT wave functions.

A case of tape infection 19 years after insertion of a tension-free vaginal tape sling.

Introduction: Tape infection after insertion of tension-free vaginal tape is a well-known but rare complication. We report a patient who experienced a subcutaneous abscess 19 years after the surgery. Case presentation: A 41-year-old woman presented with fever and lower abdominal pain. She had undergone tension-free vaginal tape insertion for stress urinary incontinence 19 years prior. She had asymptomatic dysuria. After an abscess incision and 1-week treatment with antibiotics, she underwent surgery to remove the tape and the abscess without complications. Conclusion: Tension-free Vaginal Tape insertion could be a potential risk of asymptomatic dysuria, resulting in urinary tract infection. In this case, removal of tape was necessary for controlling subcutaneous abscess resulting from the presence of tension-free vaginal tape.

An electro-mechano-optical NMR probe for 1H-13C double resonance in a superconducting magnet.

Electro-mechano-optical (EMO) NMR, an emerging NMR detection technique with signal upconversion from radiofrequency to optical regimes via a Si3N4 nanomembrane, has become compatible with NMR analysis in chemistry using a highly homogeneous but space-limited magnetic field provided by a superconducting magnet (SCM) by development of a compact EMO NMR probe operational inside the SCM bore. Optical 13C NMR signal detection following 1H-13C magnetization transfer in liquid benzene is demonstrated.

Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections.

The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants.

An adrenal incidentaloma caused by synchronous and isolated metastasis.

We report a patient with adrenal incidentaloma due to synchronous and isolated metastasis from lung cancer, which is a relatively rare condition. Close checkups for incidentaloma in oncologic patients are mandatory, leading to successful operation.

Hemodialysis vascular access infection caused by Methylobacterium radiotolerans: The first confirmed case in Japan.

Methylobacterium species are heterotrophic and fastidious Gram-negative bacilli that can be opportunistic pathogens in immunocompromised patients. These species form pink-pigmented colonies on agar plates and have been frequently isolated from tap water in hospitals. Herein, we describe a case of vascular access-related bloodstream infection caused by Methylobacterium radiotolerans in an 82-year-old man who was undergoing hemodialysis and had an implanted permanent pacemaker. Gram-negative rods cultured from his peripheral blood after incubation for 7 days were identified as M. radiotolerans by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. The patient was treated with meropenem and daptomycin for 8 days, and levofloxacin was subsequently given orally for 6 days. However, eleven days after completion of the treatment, the patient developed another febrile episode, and the vascular access line blood and his peripheral blood also grew M. radiotolerans. Meropenem and rifampicin were administered and the vascular access line was removed and replaced. Subsequently, oral levofloxacin and rifampicin treatment was maintained for 8 weeks and the patient recovered without removal of the permanent pacemaker. M. radiotolerans grew slowly in blood culture, and the isolate showed optimal growth on Reasoner's 2 Agar (R2A). To our knowledge, this is the first report of a hemodialysis vascular access-related bloodstream infection caused by M. radiotolerans in Japan. Our experience suggests that clinicians should be aware of the possibility of vascular access infection caused by M. radiotolerans.

Favorable long-term oncological and urinary outcomes of incidental prostate cancer following holmium laser enucleation of the prostate.

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

Studies on NMR-signal up-conversion from radio-frequency to optical regimes using a lightweight nanomembrane transducer.

Our recent report on Electro-Mechano-Optical (EMO) NMR proved the feasibility of up-conversion of NMR signals from radio-frequency to optical regimes using a metal-coated, high-Q membrane oscillator (Takeda et al., 2018). However, the signal-to-noise ratio, which can in principle exceed that of the conventional electrical detection scheme, was far below than ideal. Here, we developed an aluminum-coated membrane oscillator and used for a capacitor electrode as well as a mirror of an optical cavity. Compared to the gold-deposited membrane used in our previous study, the characteristic frequency of membrane oscillation was significantly higher due to mass reduction, leading to remarkable elimination of noise in the process of conversion of radio-frequency signals to the mechanical oscillation of the membrane. Taking advantage of the significantly improved EMO NMR, we explore physics behind it in terms of coherent transduction of electrical nuclear induction signals to mechanical and then to optical signals. In addition, we study the transient response of the membrane oscillator to electrical excitation due to nuclear induction.

UROLOGIC DISEASES IN THE EMERGENCY DEPARTMENT.

(Objectives) This paper aimed to report the clinical statistics on urologic diseases treated in the emergency department (ED). (Patients and methods) We retrospectively evaluated 1,480 patients diagnosed with urologic diseases in the ED between January 2013 and December 2014. We reviewed the patients' sex, age, main complaints, emergency grade, care-seeking process, hospitalization, examination items, and diagnosis. We also reviewed the correct-diagnosis rates of patients who visited the ED for the first time and were followed up at the urology department. (Results) Of the patients, 2.6% were diagnosed as having a urologic disease, with a male-to-female ratio of 1.5:1. The age distribution ranged from 0 to 101 years, with a median age of 53 years. Patients who required hospitalization accounted for 17.8%. The diagnoses were urolithiasis (546 cases), cystitis (220 cases), and pyelonephritis (137 cases), in order of frequency. The correct-diagnosis rates of urolithiasis (91.2%), benign prostatic hyperplasia (75.0%), and pyelonephritis (71.9%) were high. However, those of testicular torsion (0%), urologic neoplasm (26.7%), prostatitis (35.7%), and epididymitis (35.7%) were low. (Conclusion) In the ED, 82.2% of cases of urologic diseases were mild and did not require hospitalization. The correct-diagnosis rate of acute scrotum was low, as it was difficult to diagnose and thus difficult to manage in the ED. Therefore, urologists should cooperate with ED staff and warn them that cases of acute scrotum should be subjected to emergency consultation.

Differential diagnosis of pancreatobiliary carcinoma from autoimmune pancreatitis-related diseases: a report of three cases.

BACKGROUND: "Japanese clinical guidelines for autoimmune pancreatitis" advised to carefully differentiate between two conditions: autoimmune pancreatitis (AIP) and associated sclerosing cholangitis (SC), and pancreatobiliary malignancy. METHODOLOGY: We report a series of three cases for which differential diagnosis of pancreatobiliary carcinoma from AIP and associated SC was crucial. RESULT: Three patients presented with biliary stenosis secondary to pancreatic swelling or mass lesion, followed by further examinations: Case 1 was first diagnosed as having tumor-forming pancreatitis associated with AIP but eventually proven to be pancreatic head carcinoma; case 2 was operated for suspected bile duct cancer combined with AIP and associated cholangitis, and early cancer was found in the resected specimen; case 3 was operated on for presumed cholangiocarcinoma combined with AIP-associated SC, but no malignancy was found. CONCLUSIONS: Current series of cases would raise an alert on diagnosis of AIP and associated SC, and pancreatobiliary malignancy should be carefully excluded by any means. Surgical intervention would be required in selected cases of this clinical entity.

Age-dependent spike localization in various epileptic syndromes.

The electroencephalograms from 276 patients with localization-related epilepsy were analyzed to compare the distribution of spike foci in different age groups. Patients were divided into five groups according to spike location in the frontal, central, temporal, occipital, or multiple cortical regions. The age of peak incidence was earliest in patients with occipital foci, followed by those with central foci and then those with frontal foci. A bimodal age distribution of patients with temporal foci was observed. Symptomatic patients frequently exhibited multiple and frontal foci, and a large number of idiopathic patients had central, temporal, and occipital foci. Multiple foci were detected in 27.5% of idiopathic patients. Age-related spike localization was uniformly observed, regardless of the epileptic syndrome. The analysis of these data indicates that there are two types of multiple foci, one correlated with organic lesions and the other with an idiopathic, functional nature.