Impact of circulating microRNA test (miRNA-371a-3p) on appropriateness of treatment and cost outcomes in patients with Stage I non-seminomatous germ cell tumours.

OBJECTIVES: To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS: Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION: A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.

Rare benign and malignant testicular lesions: histopathology and management.

PURPOSE OF REVIEW: The presence of vascular solid tumors within the testicle is considered to be malignant until proven otherwise. However, it is prudent for clinicians to be aware of rare benign and malignant intratesticular lesions as management can differ from the established treatment algorithms for germ-cell tumors. RECENT FINDINGS: Utilizing certain histopathologic findings can assist with the diagnosis of rare testis tumors. Often times the tumor subtypes are an important consideration in the grading and classification of the disease, which drives management. The multidisciplinary management of rare malignant testis tumors at an experienced center seems to provide optimal patient outcomes. Regardless of the primary treatment, prolonged follow-up for sex cord stromal tumors and other rare testis malignancies is advocated due to the delayed metastatic potential. SUMMARY: The clinical presentation of rare benign and malignant testis tumors is often similar to that of germ-cell tumors. Likewise, imaging characteristics are also often indistinguishable. However, the management of these rare tumors is often different from the well established treatment algorithms of germ-cell tumors. To that end, it is important for the practicing urologist to be familiar with the current principles of these tumor characteristics and the management.

Routine Prescription of Opioids for Post-Vasectomy Pain Control Associated with Persistent Use.

PURPOSE: The AUA (American Urological Association) Position Statement on opioid use recommends using opioids only when necessary. We sought to determine if routine prescribing of opioids is necessary for pain control after vasectomy, and if an association exists with persistent use. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who underwent vasectomy in clinic between April 2017 and March 2018. Patients were stratified into 2 groups, including those initially prescribed opioids and those not receiving opioid prescriptions at the time of vasectomy. The initial pain medication regimen depended on the standard prescription practice of each provider. Encounters with a medical provider for scrotal pain within 30 days, subsequent opioid prescriptions and new persistent opioid prescriptions between 90 and 180 days were compared between the 2 groups using the Fisher exact test. RESULTS: Between April 2017 and March 2018 a total of 228 patients underwent clinic vasectomy as performed by 8 urologists. At the time of vasectomy 102 patients received opioid prescriptions and 126 received no opioid prescriptions. There was no statistically significant difference between the opioid and nonopioid groups in encounters for scrotal pain (12.7% vs 18.4%, p = 0.279). The incidence of new persistent opioid use was 7.8% in the opioid cohort compared to 1.5% in the nonopioid cohort (p = 0.046). CONCLUSIONS: Opioids, which do not appear to be necessary in men who undergo vasectomy, were associated with persistent use in 7.8% of patients at 3 to 6 months. In the face of an opioid epidemic urologists should take action to limit over prescription of opioids after vasectomy.

Longitudinal Health Related Quality of Life After Open Radical Cystectomy: Comparison of Ileal Conduit, Indiana Pouch, and Orthotopic Neobladder.

OBJECTIVE: To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. MATERIALS AND METHODS: The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. RESULTS: A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p <.005) yet still experienced similar improvements in health related quality of life commensurate with the other diversion cohorts. There was a significant difference in physical well-being favoring neobladder over IC or Indiana Pouch urinary diversions (p <.05). CONCLUSIONS: To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

Role of Neoadjuvant Chemotherapy in Squamous Variant Histology in Urothelial Bladder Cancer: Does Presence and Percentage Matter?

BACKGROUND: The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT. MATERIALS AND METHODS: The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs. ≥ 50% SV). RESULTS: The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P < .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival. CONCLUSIONS: The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has < 50% involvement by the variant histology.

Serum Small RNA Sequencing and miR-375 Assay Do Not Identify the Presence of Pure Teratoma at Postchemotherapy Retroperitoneal Lymph Node Dissection.

Existing tumor markers for testicular germ cell tumor (TGCT) cannot detect the presence of pure teratoma. Serum miRNAs have strong performance detecting other subtypes of TGCT. Previous reports suggest high levels of miR-375 expression in teratoma tissue. The purpose of this study was to explore the role of serum miRNA, including miR-375, in detecting the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We prospectively collected presurgical serum from 40 TGCT patients undergoing PC-RPLND (21 with teratoma at RPLND and 19 with no evidence of disease). We examined the utility of serum miR-375-3p and miR-375-5p by quantitative polymerase chain reaction, and searched for other putative serum miRNAs with small RNA sequencing. The area under the receiver operating characteristic curve (AUC) and univariate analyses were utilized to evaluate test characteristics and predictors of teratoma. Both serum miR-375-3p and miR-375-5p exhibited poor performance (miR-375-3p: 86% sensitivity, 32% specificity, AUC: 0.506; miR-375-5p: 55% sensitivity, 67% specificity, AUC: 0.556). Teratoma at orchiectomy was the only predictor of PC-RPLND teratoma. Small RNA sequencing identified three potentially discriminatory miRNAs, but further validation demonstrated no utility. Our results confirm prior reports that serum miR-375 cannot predict teratoma, and suggest that there may not exist a predictive serum miRNA for teratoma.

Surgical salvage in patients with advanced testicular cancer: indications, risks and outcomes.

The purpose of this review is to present a comprehensive and updated review of the literature and summary of the indications, risks and outcomes related to salvage, desperation and late relapse surgery for advanced testicular cancer. After completing a thorough review of the current literature, this review has attempted to provide an overview of the indications for salvage, desperation and late relapse retroperitoneal lymph node dissection (RPLND) followed by a summary of the histopathologic and clinical outcomes regarding each. Recent literature, combined with a significant contribution from historical studies suggest that while testicular cancer is a relatively uncommon malignancy overall, it represents the most common solid organ malignancy for young men. Although a significant number of men are cured with a combination of first-line treatments, the remaining men are a diverse and often challenging cohort who require the benefit of expertise to improve their outcomes. The role of surgical strategies in the salvage, desperation and late relapse settings is unquestionable, although the most important question remains who will benefit. This often requires a multi-disciplinary approach at centers specializing in this disease process in order to recognize who should get surgery, what surgery to do and how to minimize the potential morbidity associated with the operation.

Postchemotherapy retroperitoneal lymph node dissection in patients presenting with very high HCG levels.

PURPOSE: Choriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels. METHODS: We reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen. RESULTS: Our cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279-81.114]). CONCLUSION: While PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.

Understanding the role of salvage lymphadenectomy in node only recurrences after nephrectomy for renal cell carcinoma.

PURPOSE: To investigate oncological outcomes and relapse patterns in retroperitoneal lymph node (LN)-only recurrences with salvage retroperitoneal lymph node dissection (S-RPLND). MATERIALS AND METHODS: We reviewed records of 19 patients undergoing RPLND for RCC recurrences between 2011 and 2018. All patients initially had primary non-metastatic RCC, with subsequent recurrence restricted to the retroperitoneal lymph nodes (LN). LN recurrence sites after nephrectomy and relapses after S-RPLND were assessed. The primary outcomes were post-RPLND Relapse-Free Survival (RFS), and Cancer-Specific Survival (CSS). RESULTS: The median age of our cohort was 60 years at RPLND. Right and left nephrectomies were performed in 14 (73.7%) and 5 (26.3%), respectively. Clear cell carcinoma was found in 10 (52.6%) patients, followed by papillary in 4(21.1%), chromophobe in 2(10.5%), and 'other' in 3 (15.8%). The extent of lymphadenectomy during nephrectomy and S-RPLND varied based on surgical approach. The median follow-up time after S-RPLND of the entire cohort was 31.53 months, and the median RFS was 9.63 months. Overall, 4 patients died of cancer, of which 3 (75%) were N1 at time of nephrectomy. The CSS after RPLND at 3 and 5 years was 81.5% and 61.1%, respectively. The RFS after RPLND at 2 and 5 years was 44.4% and 29.6%, respectively. CONCLUSIONS: Our results suggest that aggressive surgical management provides satisfactory CSS with acceptable complication rates. Moreover, we believe this subset of patients with node-only recurrence showed an unpredictable pattern of lymphatic spread, with predilection for regional dissemination warranting surgical resection of LN recurrences in a bilateral template fashion when feasible.

Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline) intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7±1.8) and Dex (2.3±1.2) compared to Vehicle (3.8±0.5) group. At 3 h, urine albumin (mg/mL) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to naïve (uninjured/untreated control) (0.14±0.26) group. At 24 h post-IR urine lipocalin-2 (µg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to naïve group (0.67±0.29); also, kidney injury molecule-1 (KIM-1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7-18.7) compared to naïve group (1.7±1.9). Histopathology demonstrated reduced (P<0.05) ischemic injury in the renal cortex in VPA (Grade 1.6±1.5) compared to Vehicle (Grade 2.9±1.1). Inflammatory cytokines IL1ß and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.