Enhancing the autologous fascial sling procedure: A novel fixation method for treating stress urinary incontinence in female patients.

BACKGROUND: Synthetic mid-urethral sling surgery has long been the standard surgical treatment for stress urinary incontinence (SUI) worldwide. Using an autologous fascial sling is an alternative to reduce adverse events. We evaluated the treatment outcomes of a novel fixation method applied to the autologous transobturator fascial (TOF) sling procedure for female patients with SUI. METHODS: A retrospective study was conducted between 2017 and 2020, including 33 patients with SUI who underwent mid-urethral TOF sling surgery with the novel fixation method. We used a self-locking feature (V-LOC™) that was fixed to each side of skin layer above the obturator foramen, and the tension of the fascia sling was adjusted by manipulating the V-LOC™ suture. We analyzed all data collected through questionnaires, including Urinary Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), Overactive Bladder Symptom Score (OABSS), and Clinical Global Impressions of Improvement (CGI-I). Adverse events were also recorded. RESULTS: This study included 33 female patients aged 39-79 (mean 59.76 years). Following the procedure, there was a significant reduction in the total scores of UDI-6, IIQ-7, and OABSS (preoperative 9.73±4.35, 10.21±5.79, 6.06±4.03 and postoperative 3.52±3.41, 0.85±3.67, 3.06±2.90, respectively) (p < 0.001). Further analysis of each sub-score of the questionnaires revealed significant improvement in certain symptoms. The mean total score of CGI-I was 2.00 ± 0.80. The maximum flow rate was documented for 18 patients, and no significant reduction was observed after the procedure (p = 0.804). Complications reported included voiding dysfunction in two patients (6.1 %), inguinal pain in one patient (3.0 %), and mild delayed wound healing in one patient (3.0 %). CONCLUSION: This modified TOF sling surgery with a novel fixation method by V-LOC™ suture offers feasibility and adjustability as its main advantages. Our study demonstrated significant improvements in patient outcomes.

The lncRNA TPT1-AS1 promotes the survival of neuroendocrine prostate cancer cells by facilitating autophagy.

The lncRNA tumor protein translationally controlled 1-antisense RNA 1 (TPT1-AS1) is known for its oncogenic role in various cancers, but its impact on the pathological progression of prostate cancer remains unclear. Our previous study demonstrated that the RE1-silencing transcription factor (REST) regulates neuroendocrine differentiation (NED) in prostate cancer (PCA) by derepressing specific long non-coding RNAs (lncRNAs), including TPT1-AS1. In this study, we revealed that TPT1-AS1 is overexpressed in LNCaP and C4-2B cells after IL-6 and enzalutamide treatment. By analyzing The Cancer Genome Atlas (TCGA) prostate adenocarcinoma dataset, we detected upregulated TPT1-AS1 expression in neuroendocrine-associated PCA but not in prostate adenocarcinoma. Single-cell RNA sequencing data further confirmed the increased TPT1-AS1 levels in neuroendocrine prostate cancer (NEPC) cells. Surprisingly, functional experiments indicated that TPT1-AS1 overexpression had no stimulatory effect on NED in LNCaP cells and that TPT1-AS1 knockdown did not inhibit IL-6-induced NED. Transcriptomic analysis revealed the essential role of TPT1-AS1 in synaptogenesis and autophagy activation in neuroendocrine differentiated PCA cells induced by IL-6 and enzalutamide treatment. TPT1-AS1 was found to regulate the expression of autophagy-related genes that maintain neuroendocrine cell survival through autophagy activation. In conclusion, our data expand the current knowledge of REST-repressed lncRNAs in NED in PCA and highlight the contribution of TPT1-AS1 to protect neuroendocrine cells from cell death rather than inducing NED. Our study suggested that TPT1-AS1 plays a cytoprotective role in NEPC cells; thus, targeting TPT1-AS1 is a potential therapeutic strategy.

Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry.

PURPOSE: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. MATERIALS AND METHODS: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. RESULTS: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. CONCLUSIONS: Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Intratesticular Testosterone and Its Precursors among Azoospermic Men: A Pilot Study.

PURPOSE: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. MATERIALS AND METHODS: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. RESULTS: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. CONCLUSIONS: The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Salivary Testosterone Levels and Pain Perception Exhibit Sex-Specific Association in Healthy Adults But Not in Patients With Migraine.

This study investigated the sex-specific associations between pain perception and testosterone levels in healthy controls (HCs) and patients with migraine. Male and female HCs and migraine patients were recruited. A series of questionnaires were completed by the participants to evaluate their psychosocial profiles, which included data on mood, stress, and sleep quality. Heat pain thresholds and suprathreshold pain ratings at 45 °C (referred to as the pain perception score [PPS]) were assessed using the Thermode system. Salivary testosterone levels were analyzed using a commercial enzyme-linked immunosorbent assay kit. A total of 88 HCs (men/women: 41/47, age: 29.9 ± 7.7 years) and 75 migraine patients (men/women: 30/45, age: 31.1 ± 7.7 years) completed all assessments. No significant differences were observed in either the psychosocial profiles or heat pain thresholds and PPSs between the sexes in the control and migraine groups. A positive correlation between testosterone levels and PPSs was identified in the male controls (r = .341, P = .029), whereas a negative correlation was identified in the female controls (r = -.407, P = .005). No such correlations were identified in the migraine group. This study confirms that a negative association is present between PPSs and testosterone levels in female controls, which is in line with the findings that testosterone is associated with reduced pain perception. Our study is the first to demonstrate a sex-specific association between PPSs and testosterone levels in HCs. Moreover, this study also revealed that the presence of migraine appears to disrupt this association. PERSPECTIVE: This study revealed that testosterone levels demonstrate opposite associations with pain perception in healthy men and women. However, the presence of migraine appears to disrupt this sex-specific association.

Survival outcomes of radium-223 therapy for metastatic castration-resistant prostate cancer following national health insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 dichloride (Ra-223) prolongs overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases. However, there is considerable variation in outcomes among individuals. We aimed to evaluate the prognostic determinants associated with patient survival following National Health Insurance (NHI) reimbursement for Ra-223 therapy in Taiwan. METHODS: Patients with mCRPC who underwent Ra-223 treatment at Taipei Veterans General Hospital were retrospectively enrolled. Each intravenous Ra-223 dose was administered at 55 kBq/kg at 4-week intervals. Clinical outcomes were obtained from medical records; potential prognostic factors for survival were assessed. Kaplan-Meier analysis was used to generate cumulative survival curves; between-group differences were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05. RESULTS: Seventy-six patients underwent Ra-223 therapy; 62 patients received NHI reimbursement and the remainder self-paid. Fifty patients (65.8%) completed six cycles of treatment; 26 (34.2%) received 1 to 5 cycles. Mortality occurred in 47 patients. Factors significantly associated with survival included ≤five bone metastases ( p = 0.0018), baseline prostate-specific antigen (PSA) ≤36 ng/mL ( p = 0.0004), baseline alkaline phosphate (ALP) <115 U/L ( p = 0.0007), and baseline hemoglobin (Hb) >12 g/dL ( p = 0.0029). Patients who completed six cycles of treatment achieved significantly higher OS compared to those who did not ( p < 0.0001). There has been a 4.4-fold increase in the number of patients since reimbursement began; there was no significant difference in OS between patients who received NHI reimbursement and those who self-paid. CONCLUSION: Administration of Ra-223 demonstrates considerable potential to extend the survival of patients with mCRPC. Survival outcomes may be influenced by various prognostic factors. However, no significant difference in OS was observed subsequent to reimbursement of Ra-223 therapy for mCRPC through the NHI system in Taiwan.

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Single-cell analysis of castration-resistant prostate cancers to identify potential biomarkers for diagnosis and prognosis of neuroendocrine prostate cancer.

The high heterogeneity and low percentage of neuroendocrine cells in prostate cancer limit the utility of traditional bulk RNA sequencing and even single-cell RNA sequencing to find better biomarkers for early diagnosis and stratification. Re-clustering of specific cell-type holds great promise for identification of intra-cell-type heterogeneity. However, this has not yet been used in studying neuroendocrine prostate cancer heterogeneity. Neuroendocrine cluster(s) were individually identified in each castration-resistant prostate cancer specimen and combined for trajectory analysis. Three neuroendocrine states were identified. Neuroendocrine state 2 with the highest AR score was considered the initial starting state of neuroendocrine transdifferentiation. State 1 and state 3 with distinct high neuroendocrine scores and marker genes enriched in N-Myc and REST target genes, respectively, were considered as two different types of neuroendocrine differentiated cancer cells. These two states contained distinct groups of prostate cancer biomarkers and a strong distinguishing ability of normal versus cancerous prostate across different pathological grading was found in the N-Myc-associated state. Our data highlight the central role of N-Myc and REST in mediating lineage plasticity and classifying neuroendocrine phenotypes.

REST-repressed lncRNA LINC01801 induces neuroendocrine differentiation in prostate cancer via transcriptional activation of autophagy.

The association between REST reduction and the development of neuroendocrine prostate cancer (NEPC), a novel drug-resistant and lethal variant of castration-resistant prostate cancer (CRPC), is well established. To better understand the mechanisms underlying this process, we aimed to identify REST-repressed long noncoding RNAs (lncRNAs) that promote neuroendocrine differentiation (NED), thus facilitating targeted therapy-induced resistance. In this study, we used data from REST knockdown RNA sequencing combined with siRNA screening to determine that LINC01801 was upregulated and played a crucial role in NED in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma database and CRPC samples collected in our laboratory, we demonstrated that LINC01801 expression is upregulated in NEPC. Functional experiments revealed that overexpression of LINC01801 had a slight stimulatory effect on the NED of LNCaP cells, while downregulation of LINC01801 significantly inhibited the induction of NED. Mechanistically, LINC01801 is transcriptionally repressed by REST, and transcriptomic analysis revealed that LINC01801 preferentially affects the autophagy pathway. LINC01801 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of autophagy-related genes by sponging hsa-miR-6889-3p in prostate cancer cells. In conclusion, our data expand the current knowledge of REST-induced NED and highlight the contribution of the REST-LINC01801-hsa-miR-6889-3p axis to autophagic induction, which may provide promising avenues for therapeutic opportunities.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Proteomic Analysis of Testicular Interstitial Fluid in Men with Azoospermia.

Background: The primary microenvironment of the testis comprises testicular interstitial fluid (TIF) surrounding the seminiferous tubules and testicular interstitial tissue. The pathological alterations of germ and Sertoli cells could affect the TIF composition and might contain putative biomarkers for monitoring active spermatogenesis. Objective: We identified differentially expressed proteins in the TIF of patients with obstructive (OA) or nonobstructive (NOA) azoospermia to elucidate the underlying etiology of defective spermatogenesis. Design setting and participants: We prospectively enrolled nine patients, including three men with OA and six with NOA with (n = 3) and without (n = 3) successful sperm retrieval. Their TIF was collected during the testicular sperm extraction procedure. Outcome measurements and statistical analysis: TIF was analyzed using liquid chromatography-tandem mass spectrometry to identify differentially expressed proteins specific to OA and NOA with or without successful sperm retrieval. The dysregulated protein was further validated using Western blotting. Results and limitations: Among the 555 TIF proteins identified in NOA patients, 14 were downregulated relative to OA patients. These proteins participate in biological processes such as proteolysis, complement activation, and immune responses; complement and coagulation cascade pathways were also enriched. Furthermore, 68 proteins with significantly higher levels were identified in the TIF of NOA patients with successful sperm retrieval than in those with failed sperm retrieval; these are mainly implicated in oxidation-reduction processes. The expression of calreticulin, which can distinguish successful and failed testicular sperm retrieval in the NOA group, was validated by Western blotting. Conclusions: We provide the first scientific evaluation of TIF protein composition in men with azoospermia. These findings will help identify the physiological and pathological roles of each protein in regulating sperm production. Thus, our study underscores the potential of TIF in sperm retrieval biomarker discovery and would serve as a foundation for further studies to improve treatment strategies against azoospermia. Patient summary: Using a proteomic approach, we identified and analyzed the total protein content of testicular interstitial fluid in humans with defective spermatogenesis for the first time and discovered altered protein expression patterns in patients with nonobstructive azoospermia (NOA). Proteins related to oxidation-reduction processes were upregulated in NOA patients with successful sperm retrieval compared with those with failed sperm retrieval. This can aid the development of novel diagnostic tools for successful testicular sperm retrieval.

Effects of different combinations of radical nephroureterectomy and bladder cuff excision procedures for upper tract urothelial carcinoma on bladder recurrence

ABSTRACT Purpose: To compare the effects of different combinations of radical nephroureterectomy (RNU) and bladder cuff excision (BCE) surgical procedures on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). Materials and Methods: This retrospective observational study included 452 patients who underwent RNU with BCE for UTUC between January 2010 and December 2020. The patients were classified into three groups based on different combinations of RNU and BCE surgical procedures: open RNU with open BCE (group 1, n=104), minimally invasive (MIS) RNU with open BCE (group 2, n=196), and MIS RNU with intracorporeal BCE (group 3, n=152). Data on demographics, body mass index, history, preoperative renal function, perioperative status, tumor characteristics, histopathology, and recurrence conditions were collected. Multivariate Cox regression analyses were performed to determine the impact of the surgical procedures on IVR. P-values <0.05 were considered statistically significant. Results: After a median follow-up of 29.5 months, the IVR rate was 29.6% and the IVR-free survival rate was the lowest in group 2 (group 1 vs. group 2 vs. group 3: 69.0% vs. 55.1% vs. 67.5%; log-rank P=0.048). The overall survival rate was comparable among the three groups. Multivariate analysis revealed that group 2 had a significantly higher risk of IVR than group 1 (hazard ratio=1.949, 95% confidence interval=1.082-3.511, P=0.026), while groups 1 and 3 had similar risks. Conclusions: For patients with UTUC, MIS RNU with open BCE is associated with a higher risk of IVR than open RNU with open BCE and MIS RNU with intracorporeal BCE.

Prediction of microdissection testicular sperm extraction outcomes of azoospermic patients post-chemotherapy using cyclophosphamide equivalent dose.

PURPOSE: We determined the sperm retrieval rate in men with persistent azoospermia post-chemotherapy in relation to cyclophosphamide equivalent dose (CED), a unit for quantifying alkylating agent exposure. METHODS: Medical records were retrospectively reviewed of 1098 patients diagnosed with non-obstructive azoospermia who had undergone microdissection testicular sperm extraction (mTESE) between January 2010 and 2021 at our institution. Twenty-three patients with a prior history of chemotherapy were included in the study. Oncological data, chemotherapy regime, and dosage were reviewed. The pretreatment hormone profile, CED, and mTESE outcomes were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved from 11 patients (47%). The mean patient age was 37.3 years (range, 27-41 years), and mean time interval from chemotherapy to mTESE, 11.8 years (range, 1-45 years). Patients exposed to alkylating agents had significantly lower sperm retrieval rates than those not exposed to alkylating agents (1/9, 11% vs. 10/14, 71%, p = 0.009). No men with CED > 4000 mg/m2 (n = 6) had viable sperm in the testes during mTESE. Moreover, patients diagnosed with testicular non-seminomatous germ cell tumors had a favorable sperm retrieval rate (67%) compared to patients with lymphoma (20%) or leukemia (33%). CONCLUSION: Patients with permanent azoospermia post-chemotherapy have a lower testicular sperm retrieval rate when the chemotherapy regimen included alkylating agents. In cases where patients have undergone more intensive gonadotoxic treatments, such as higher CED, the likelihood of successful sperm retrieval is low. It is advisable to counsel such patients using the CED model prior to considering surgical sperm retrieval.

Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan.

BACKGROUND: Radium-223 (Ra-223), an α-particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute. METHODS: Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS). RESULTS: Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance. CONCLUSION: The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.

Effects of different combinations of radical nephroureterectomy and bladder cuff excision procedures for upper tract urothelial carcinoma on bladder recurrence.

PURPOSE: To compare the effects of different combinations of radical nephroureterectomy (RNU) and bladder cuff excision (BCE) surgical procedures on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: This retrospective observational study included 452 patients who underwent RNU with BCE for UTUC between January 2010 and December 2020. The patients were classified into three groups based on different combinations of RNU and BCE surgical procedures: open RNU with open BCE (group 1, n=104), minimally invasive (MIS) RNU with open BCE (group 2, n=196), and MIS RNU with intracorporeal BCE (group 3, n=152). Data on demographics, body mass index, history, preoperative renal function, perioperative status, tumor characteristics, histopathology, and recurrence conditions were collected. Multivariate Cox regression analyses were performed to determine the impact of the surgical procedures on IVR. P-values < 0.05 were considered statistically significant. RESULTS: After a median follow-up of 29.5 months, the IVR rate was 29.6% and the IVR-free survival rate was the lowest in group 2 (group 1 vs. group 2 vs. group 3: 69.0% vs. 55.1% vs. 67.5%; log-rank P=0.048). The overall survival rate was comparable among the three groups. Multivariate analysis revealed that group 2 had a significantly higher risk of IVR than group 1 (hazard ratio=1.949, 95% confidence interval=1.082-3.511, P=0.026), while groups 1 and 3 had similar risks. CONCLUSIONS: For patients with UTUC, MIS RNU with open BCE is associated with a higher risk of IVR than open RNU with open BCE and MIS RNU with intracorporeal BCE.

Touch print smear of testicular tissue with thionine stain for intraoperative diagnosis in azoospermic men.

PURPOSE: To compare the diagnostic value of testicular tissue touch print smear (TPS) conducted on azoospermic patients with results obtained from histopathology and in vitro fertility (IVF) lab findings. METHODS: Microdissection testicular sperm extraction was performed on a group of 148 azoospermic patients and testicular samples obtained intraoperatively. Using TPS, the samples were smeared onto a sterile slide, followed with staining using thionine. The testis tissue bulk samples were also transferred to the IVF lab, and determinations of sperm presence or absence obtained from IVF lab tests were compared with the TPS sample results. Needle testis biopsy was separately performed on a group of 360 azoospermic patients, and results of pathohistology review on the biopsies were further compared with determinations of spermatogenesis stage obtained from TPS for those patients. RESULTS: When compared with IVF lab results, TPS was found to have 100% (126/126) positive predictive value and 95.5% (25/26) negative predictive value for predicting sperm presence or absence, respectively. Furthermore, TPS was further found to have a 93.6% correlation (337 of 360 biopsies) with results of histological diagnoses performed by needle biopsy. Results from histology and TPS for the detection of sperm presence were concordant in 96.1% (346/360) of biopsies. Diagnosis of SCO by TPS shows the highest correlation with histopathology (98.6%), followed by complete spermatogenesis (97.5%), early maturation arrest (78.9%), and late maturation arrest (27.3%). CONCLUSIONS: The results support the continued use of TPS in testicular tissue analysis for more rapid assessment of spermatogenesis and for detection of spermatozoa in azoospermic subjects.

Comparison of stone-free rate between percutaneous nephrolithotomy and retrograde intrarenal surgery.

BACKGROUND: The management of urolithiasis in the kidney has been drastically changed in the era of endourology, mainly consisting of three surgical procedures: extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS). Since ESWL is usually less invasive via ambulatory clinic routes, this study aimed to examine the stone-free rate (SFR) between PCNL and RIRS. METHODS: We retrospectively reviewed patients who had renal stones and were treated with either PCNL or RIRS from June 2016 to June 2018. Staghorn stones, stones with diameters <1 cm, and stones with diameters >2 cm were excluded. Patients who underwent multiple surgeries for bilateral renal stones and those with graft kidney stones were excluded from the study. X-ray, sonography, and/or computed tomography (CT) were used to calculate the size of the stones. Follow-up was evaluated by the same image examination within three months after surgery. Stone-free was defined as no residual stone or the presence of asymptomatic calculi <4 mm. The operation time was defined as a skin-to-skin interval. RESULTS: Following exclusion criteria, there were 39 patients in each arm, with no difference in age, sex, or any other demographic data. The average stone size in the PCNL and RIRS groups was 16.3 and 14.0 mm, respectively ( p = 0.009). There was no significant difference in SFR (71.8% vs 61.5%, p = 0.337); the operation time was significant longer ( p < 0.001), and the hospital stay was significantly shorter ( p < 0.001) in the RIRS group. CONCLUSION: PCNL and RIRS are both feasible options for managing kidney stones. However, the initial stone size might affect the selection of operation. The SFR in the PCNL group was numerically but not statistically higher. The RIRS group, on the other hand, had a longer operation time but a shorter hospital stays.

Risk factors for hemorrhagic complications following robotic-assisted partial nephrectomy.

BACKGROUND: The aim of this study was to analyze the risk factors for hemorrhagic complications in patients who underwent robotic-assisted partial nephrectomy. METHODS: We retrospectively reviewed the records of 260 patients who underwent robotic-assisted partial nephrectomy. Hemorrhagic complications were defined as bleeding, hematoma, or arteriovenous fistula requiring hemostatic medication, blood transfusion, or therapeutic intervention. Hemorrhagic complications were graded according to the modified Clavien classification system, and the hemorrhagic complication group comprised only those complications with Clavien grade II or higher. Thereafter, we investigated the presence of any relevant association between perioperative factors and hemorrhagic complications. RESULTS: Of 260 patients included in the study, 32 (12.3%) had hemorrhagic complications. The postoperative hemoglobin level was significantly lower in the hemorrhagic complication group than in the group without complications. The hemorrhagic complication group had significantly more essential blood loss and a significantly longer length of hospital stay. In the univariate analysis, type 2 diabetes mellitus, Radius-scores tumor size as maximal diameter exophytic/endophytic properties of the tumor nearness of the deepest portion of the tumor to the collecting system or renal sinus anterior (a)/posterior (p) descriptor location relative to the polar line., sum of the renal size plus renal sinus involvement in the PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS, prolonged console time (>180 minutes), prolonged warm ischemic time (>25 minutes), and method of pedicle control were statistically significant risk factors. In the multivariate logistic regression analysis, warm ischemic time >25 minutes was the only significant risk factor for hemorrhagic complications (odds ratio, 3.51; 95% confidence interval, 1.28-9.59; p = 0.01). CONCLUSION: Patients who undergo robotic-assisted partial nephrectomy with a warm ischemic time >25 minutes are significantly more likely to have hemorrhagic complications and should hence receive careful perioperative follow-up.

Consensus of Experts on the Treatment of Sexual Dysfunction after Surgery for Prostate Cancer in Taiwan.

According to the Taiwan Cancer Report, in 2018, prostate cancer was one of the top five cancers reported in men. Each year, many patients with prostate cancer undergo radical prostatectomy (RP) therapy. One of the most common RP complications is erectile dysfunction (ED). Although consensus guidelines for the management of sexual dysfunction after prostate cancer surgery have been developed for many Western and Asian countries, no such clinical practice guidelines have been developed for Taiwan. The consensus opinions expressed in this article were discussed by numerous experienced physicians in Taiwan, based on both existing international guidelines and their individual experiences with clinical trials and providing advice to clinical physicians on how to inform patients of the risk of ED prior to surgery. This review also discusses how recovery and rehabilitation may be affected by socioeconomic status, the existence of an intimate relationship, comorbidities, or the need for cancer adjuvant therapy and how to determine rehabilitation goals and provide appropriate treatments to assist in the recovery of both short- and long-term sexual function.