PurposeTouch print smear (TPS) of testicular specimens provides immediate diagnostic results comparable to histopathology and in vitro fertilization laboratory findings. This study aimed to validate TPS as a rapid complement to histopathology for detecting post-meiotic germ cells in azoospermic patients.Materials and methodsWe retrospectively analyzed 495 azoospermic patients (274 with obstructive azoospermia [OA]) who underwent testis needle biopsy (2015-2022). Specimens were immediately smeared onto sterile slides, then transferred into Bouin's solution for pathological diagnosis. Slides were stained with thionine and examined under light microscopy. Spermatogenesis development was compared between TPS findings and histopathology.ResultsTPS and histopathology were concordant in 98.2% (269/274) of OA and 75.6% (167/221) of non-obstructive azoospermia (NOA) cases. Among discordant NOA patients, 74.1% (40/54) showed more advanced spermatogenesis with TPS. Of 20 patients in whom post-meiotic germ cells were identified by TPS but not by histopathology, 95% (19/20) achieved successful sperm retrieval during subsequent microdissection testicular sperm extraction (mTESE). Conversely, in NOA patients where TPS suggested less advanced spermatogenesis and failed to identify post-meiotic germ cells, the sperm retrieval rate was 57.1% (4/7).ConclusionTPS allows rapid identification of post-meiotic germ cells with excellent concordance in OA and provides clinically relevant information in NOA. Patients in whom TPS demonstrates post-meiotic germ cells have a high likelihood of sperm retrieval, whereas their absence on TPS indicates lower retrieval success, in which case histopathology remains a useful backup.

BACKGROUND:In this study, we aimed to evaluate the proportion of nonobstructive azoospermia (NOA) cases exhibiting features resembling the obstructive azoospermia (OA) phenotype and assess the applicability of the Schoor criteria in an East Asian cohort. METHODS:We retrospectively reviewed azoospermic patients who presented with low follicle-stimulating hormone level (≤9.2 IU/L) and large testicular volume (≥15 mL), consistent with the "phenotypical OA (phOA)" criteria proposed by Huang et al. All patients underwent a testicular biopsy to confirm the pathological diagnosis. Complete spermatogenesis was considered the key feature of "pathological OA (pOA)." RESULTS:A total of 271 patients with azoospermia were included in the analysis. Among them, 222 (81.9%) exhibited complete spermatogenesis consistent with pOA, whereas 49 (18.1%) were diagnosed with pathological NOA (pNOA). According to the Schoor criteria, 17 patients were classified as phOA; however, two (11.8%) were subsequently confirmed to have pNOA. Conversely, 31 patients were classified as having phNOA, of whom 23 (74.2%) demonstrated pOA on testicular biopsy. Under the Schoor criteria, the positive predictive value (PPV) for pOA was 88.2%, and the negative predictive value (NPV) for pOA was 25.8%. Using the Huang criteria, 49 of 271 patients (18.1%) met the definition of phOA but were diagnosed as pNOA on biopsy (ie, false positives), yielding a PPV of 81.9% for pOA. CONCLUSION:The Schoor criteria, derived from a Caucasian cohort, may be unsuitable for East Asian patients, given the much lower NPVs for pOA in our cohort (25.8%) than that in the Schoor study (92.3%). These findings highlight the limitations of relying solely on clinical criteria, either Schoor or Huang, to guide sperm retrieval strategies, including the choice of retrieval method and microsurgical approach. Therefore, a testicular biopsy is essential to confirm complete spermatogenesis in patients with clinically phOA.

BackgroundCurrent guidelines recommend endocrine evaluation for infertile men; however, those with normal sperm concentration (≥15 million/mL) may be under-referred for comprehensive assessment. This study aimed to investigate the prevalence of low testosterone in infertile men with normal sperm concentration and to determine the proportion who remain endocrinologically unevaluated.MethodsA retrospective review was conducted on infertile men with initial sperm concentration ≥15 million/mL evaluated at a single tertiary center from January 2013 to December 2020. Low testosterone was defined as serum total testosterone below 300 ng/dL. Multivariate logistic regression identified independent predictors of low testosterone.ResultsOf 3,147 men meeting inclusion criteria, 77.2% (n=2,429) did not undergo hormonal evaluation. Endocrine assessment rates varied significantly by specialty: 100% for male infertility fellowship-trained urologists, 23.2% for general urologists, and 1.2% for gynecologists. Among 718 men who underwent hormonal testing, 24.1% had low testosterone. Multivariate logistic regression identified higher BMI (OR 1.083, 95% CI 1.031–1.136, p=0.001) and lower estradiol (OR 0.956, 95% CI 0.937–0.976, p<0.001) as independent predictors. Obese men had significantly higher odds of low testosterone compared with normal-weight men (OR 1.725, 95% CI 1.010–2.943, p=0.046). Of 66 treated men, significant testosterone increases were observed at all follow-up time points (all p ≤ 0.001), and six achieved natural pregnancy.ConclusionOver three-quarters of normozoospermic infertile men did not receive hormonal evaluation. Among those evaluated, nearly one-quarter had low testosterone, with obesity identified as an independent risk factor. These findings highlight a critical screening gap and support routine endocrine screening regardless of sperm concentration, particularly in men with metabolic risk factors such as obesity, as low testosterone represents a treatable condition that may improve fertility outcomes.

BACKGROUND:Upper tract urothelial carcinoma is an aggressive malignancy originating from the transitional epithelium of the urinary tract. UTUC patients with pre-existing end stage renal disease (ESRD) have limited perioperative treatment options due to severely impaired bilateral kidney functions. We therefore sought to identify targetable oncogenic mechanisms in this patient population. METHODS:A single-center retrospective study analyzed 50 fresh frozen UTUC tumor samples (17 with ESRD, 33 without) using RNA sequencing for transcriptomics profiling. Gene set enrichment analysis was performed to identify gene sets collectively enriched in ESRD tumors, with normalized enrichment score (NES) used to standardize enrichment magnitude across sets of varying sizes. Regular hemodialysis prior to UTUC diagnosis was used to identify patients with ESRD. Immunohistochemical staining was conducted on paraffin-embedded slides (6 with ESRD, 7 without) to demonstrate the involvement of representative proteins in the gene set. Candidate drugs were ranked via Connectivity Map analysis, and the drug with the highest inhibition score were further assessed through in vitro cell viability and migration assays. RESULTS:Because overall and cancer‑specific survival did not differ significantly between groups, we interpreted transcriptomic differences as intrinsic tumor characteristics rather than consequences of disease severity. TBK1-associated gene sets were enriched in ESRD-UTUC patients (NES = 2.065, FDR q value = 0.001). Immunohistochemistry confirmed higher TBK1 levels in ESRD tissues (P = .044). A IKK/NF-κB inhibitor, Withaferin A (CAS No. 5119-48-2), emerged as a leading candidate drug (score of inhibition = 2.521). The in vitro assays demonstrated the effectiveness of Withaferin A in reducing the viability and migration of UTUC cells, suggesting potential for further clinical investigation. CONCLUSIONS:The TBK1-associated oncogenic mechanism is prominent in UTUC patients with preexisting ESRD. Withaferin A demonstrates preclinical promise as a therapeutic candidate targeting this mechanism in UTUC patients with compromised renal function.

Post-prostatectomy continence status, in addition to lower urinary tract symptoms, is a major concern among patients after robotic-assisted radical prostatectomy (RaRP). In this prospective study, we enrolled patients undergoing RaRP to evaluate subjective urinary symptoms and objective urodynamic parameters before and after surgery. Patients were recruited before RaRP surgery between January 2019 and August 2020. One day before surgery, the participants completed three questionnaires and pressure-flow studies, which were repeated approximately 3 months postoperatively. Of the total 135 patients initially enrolled, 85 (63.0%) completed the entire follow-up period. Three months after RaRP, the International Prostate Symptom Score showed significant increases in storage symptoms. Similar trends were observed in the Urinary Distress Inventory Short Form, and Overactive Bladder Symptom Score questionnaires. More than half of the patients regained continence within 2 months, although 9.6% remained incontinent after 1 year. Postoperative urodynamic studies indicated increased bladder hypersensitivity and significantly decreased detrusor pressure at peak flow. Furthermore, the bladder contractility index and bladder outlet obstruction index were reduced postoperatively. Ten patients (11.8%) developed de novo detrusor overactivity. The multivariate analysis identified age and cross-sectional area of the bladder neck as predictors of immediate continence after RaRP.

Background:Neuroendocrine prostate cancer (NEPC) (de novo or treatment-related [t-NEPC]) is a rare and deadly variant of prostate cancer. While de novo NEPC is rare, t-NEPC occurs more frequently in patients with castration-refractory prostate cancer. Owing to the rarity of NEPC, no standard treatment has been established, and the outcomes are generally unsatisfactory.Methods:This study retrospectively reviewed NEPC cases at Taipei Veterans General Hospital between 2018 and 2023. Clinical outcomes, treatment modalities, and related genomic profiles were recorded. We also performed a literature review of case series reporting the outcomes of chemotherapeutic regimens for NEPC.Results:From 2158 cases of prostate cancer cases diagnosed during the study period, only 7 had pathologically proven NEPC (0.3%), and the median overall survival was 364 days. Three patients who underwent multigene panel sequencing had mutations in RB1, and delta-like ligand 3 (DLL3) immunohistochemical staining showed a positivity rate of 50%. We performed a literature review on chemotherapy outcomes in patients with NEPC. In six studies with 104 patients, etoposide + platinum treatment was most commonly used. The progression-free survival (PFS) and overall survival ranged from 3.4 to 9.3 and 8.4 to 22.4 months, respectively. The response rates ranged from 44% to 69.2%. These studies were consistent with a dismal overall survival rate, despite a high response rate to the initial chemotherapy regimen.Conclusion:Our study reported poor outcomes with chemotherapy, with a high frequency of retinoblastoma protein (RB) loss and DLL3 positivity. Further clinical developments targeting DLL3 are warranted.