Comparison of EEP and TURP long-term outcomes: systematic review and meta-analysis.

OBJECTIVE: To compare long-term reoperation rate and functional outcomes between EEP (endoscopic enucleation of the prostate) and TURP (transurethral resection of the prostate). EVIDENCE ACQUISITION: A systematic literature review of Medline, Scopus, and Web of Science was conducted with primary outcome assessed being reoperation rate and secondary outcomes after a long term (> 3 years) being functional outcomes or related values (prostate volume, PSA level, etc.). EVIDENCE SYNTHESIS: Five studies were found with long-term follow-up 4-7 years. EEP reoperation rate ranged from 0 to 1.27%, while from 1.7 to 17.6% for TURP. Meta-analysis showed significantly lower OR for EEP, 0.27 (95% CI 0.24-0.31), with notable homogeneity of the results, I2 = 0%. Long-term Qmax and IPSS were significantly better for EEP. Qmax pooled mean difference was 1.79 (95% CI 1.72-1.86) ml/s with a high concordance among the studies, I2 = 0%. IPSS mean difference -1.24 (95% CI - 1.28 to - 1.2) points, I2 = 57% but QoL did not differ, with mean difference being 0.01 (95% CI - 0.02 to 0.04), I2 = 0%. IIEF-5 score was also significantly better for EEP, mean difference 1.08 (95% CI 1.03-1.13), but heterogeneity was high, I2 = 70%. PSA level and prostate volume were only reported in one study and favored EEP slightly yet statistically significant. CONCLUSION: EEP had a significantly lower reoperation rate and better functional outcomes (Qmax and IPSS) at long term compared with TURP. It may also be beneficial in terms of IIEF-5, PVR, and PSA level.

Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Tubeless supra-costal percutaneous nephrolithotomy is associated with significantly less hydrothorax: a prospective randomized clinical study.

OBJECTIVES: To evaluate prospectively whether a tubeless (JJ stent-only) percutaneous nephrolithotomy (PCNL) might reduce the risk of hydrothorax, compared to an approach where a nephrostomy tube is left. MATERIALS AND METHODS: We conducted a two-arm open-label prospective randomized study (NCT02036398) comparing tubeless supra-costal PCNL (with a JJ stent only) to standard PCNL (with nephrostomy tube and JJ stent) using intention-to-treat (ITT) and per-protocol (PP) analyses. All patients underwent a standard single-stage prone supra-costal procedure with single-tract access. Complication data were collected according to the Clavien-Dindo grading system. The primary endpoint was the rate of hydrothorax, and secondary endpoints included stone-free rate (SFR) and complication rate. Multivariable logistic regression analysis identified factors associated with hydrothorax formation. RESULTS: Out of 101 patients approached, 75 were finally analysed. No differences were observed between the two arms with regard to baseline demographic and stone characteristics. The mean largest stone size ranged between 23 and 24.2 mm. No significant difference was seen in the mean operating time and length of hospital stay. The incidence of hydrothorax was significantly higher in the nephrostomy group in comparison to the tubeless group (37.8% vs 15.8%, P = 0.031, and 38.4% vs 13.8%, P = 0.016, in the ITT and PP analyses, respectively). The SFR and complication rate were similar in both groups using the ITT and PP analyses. Multivariable logistic regression analysis showed that nephrostomy tube placement was the only covariate associated in a statistically significant manner to hydrothorax (odds ratio 3.628, 95% confidence interval 1.073-12.265; P = 0.038). CONCLUSION: The rate of hydrothorax in supra-costal PCNL is associated with the type of postoperative drainage left. When possible, a tubeless approach should be applied as it may confer a lower risk of hydrothorax.

Propensity Score-Matched Analysis of Perioperative Outcomes of Supine versus Prone Percutaneous Nephrolithotomy.

Objective: To compare the perioperative outcomes of supine and prone percutaneous nephrolithotomy (PCNL). Methods: A retrospective search of a tertiary medical center database yielded 517 patients who underwent supine (n = 91) or prone (n = 426) PCNL between September 2015 and July 2020. Data on demographics, baseline clinical parameters, and stone burden were included as predictors in a logistic regression model, generating a set of propensity scores. Seventy patients after supine PCNL were propensity score-matched 1:1 with patients after prone PCNL and compared for operative time, perioperative complications, system complexity, and stone-free rate. Results: We found that the operative time was significantly shorter in the supine PCNL group than in the prone PCNL group (85.5 ± 25.2 min vs. 96.4 ± 25.8 min, respectively; p = 0.012). The majority of both groups had low-grade (I-II) complexity systems (85.6% and 88.6%, respectively), with no significant difference among all grade groups (p = 0.749). There were no significant differences between the supine and prone PCNL groups in terms of the overall perioperative complication rate (8.6% vs. 4.3%, respectively; p = 0.301) or stone-free rate (74.3 vs. 65.7%, respectively; p = 0.356), while the rate of blood transfusion was significantly higher in the supine group (p = 0.023). Conclusions: In our study, we used propensity score matching to compare patients who underwent PCNL in the supine or prone position, adjusting for selection bias. Supine PCNL was associated with a shorter operative time but a higher blood transfusion rate, with no differences in the overall complication and stone-free rates.

Late relapse of testis cancer.

Most relapses of germ-cell tumors occur within 2 years of initial treatment. In 2 % to 4 % of patients, relapse may occur later. The retroperitoneum is the primary site of late relapses, and alpha-fetoprotein is the predominant marker. These tumors are highly resistant to chemotherapy. Surgical resection is the preferred treatment. If the recurrent disease is inoperable, salvage chemotherapy may be instituted, followed by resection of the residual disease.

Retrograde intrarenal surgery for lower pole stones utilizing stone displacement technique yields excellent results.

Objective: To evaluate the long-term stone-free rate (SFR) of retrograde intra-renal surgery (RIRS) in the treatment of lower pole renal calculi using only basket relocation and identify independent predictors of stone-free status. Methods: All consecutive patients undergoing RIRS lower pole renal calculi at a single high-volume tertiary center were analyzed retrospectively. Lower pole stones were relocated to the upper pole, where laser lithotripsy was performed. All patients were followed up in the clinic following the surgery and yearly thereafter. The stone-free status was assessed with a combination of an abdominal ultrasound and abdominal X-ray, or an abdominal non-contrast computed tomography if the stones were known to be radiolucent. Results: A total of 480 consecutive patients who underwent RIRS for treatment of lower pole renal calculi, between January 2012 and December 2018, were analyzed from a prospectively maintained database of 3000 ureteroscopies. With a median follow-up time of 18.6 months, the mean SFR was 94.8%. The procedures were unsuccessful in 26 (5.4%) patients due to unreachable stones. The median stone size of the unreachable stones was 12 mm (range 10-30 mm). Multivariable logistic regression analysis revealed two predictors of SFR for lower pole stones: a small cumulative stone burden (odds ratio [OR]: 0.903, 95% confidence interval [CI]: 0.867-0.941, p<0.0001) and preoperative ureteral stent insertion (OR: 0.515, 95% CI: 0.318-0.835, p=0.007). Conclusion: The long-term SFR of RIRS for the treatment of lower pole stones with basket displacement with appropriate patient selection is high.

Endoscopic Management of Low-Grade Upper Tract Urothelial Carcinoma: Characterizing the Long-term Burden of Care in Comparison to Radical Nephroureterectomy.

OBJECTIVE: To compare procedure burden, oncologic, surgical and renal-function outcomes between patients with low-grade upper urothelial cancer (UTUC) who were referred for either radical management (RM) or kidney-sparing endoscopic management (EM). PATIENTS AND METHODS: We retrospectively reviewed data of all patients treated for UTUC at our tertiary medical center between 2000 and 2018 and selected patients diagnosed with unilateral low-grade UTUC. RESULTS: Twenty-four patients were treated with EM and 37 with RM. Surgical and oncologic risk factors were similar between the arms except for tumor size. Mean follow-up was 4.9 ± 3.4 years. The 5-year overall-survival rate was 85% with EM and 84% with RM (P = .707). Metastasis-free and cancer-specific survival were also similar (P = .994, P = .960). End-of-follow-up average glomerular filtration rates were 58.7 ± 21.5 and 49.2 ± 22.1 mL/min/1.73 m2, respectively (P = .12). Ninety-two percent of patients managed endoscopically had local recurrences, with an average of 3.2 recurrences per patient. Four (17%) patients underwent salvage radical nephroureterectomy. Procedure burden was higher with EM, having 6.5 ± 4.4 operations and 344 ± 272 minutes under anesthesia compared with 1.9 ± 0.4 operations (P <.0001) and 213 ± 84 minutes under anesthesia (P = .031) with RM. Cost-of-care analysis revealed higher costs for EM in both private and publicly funded medical insurance plans. CONCLUSION: Patients undergoing endoscopic management had an 83% chance of preserving their kidney and an 81% chance of 5-year metastasis-free survival at a cost of 6.5 ± 4.4 operations during a mean follow-up of 4.9 ± 3.4 years. Our findings support EM for low-grade UTUC as a valid option from oncological aspects but highlight the associated costs.

Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements.

Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy. Improved treatments, including targeted therapy, require understanding the biology of these neoplasms. We therefore analyzed the morphologic, immunohistochemical and molecular biologic features of 14 PNETs from 14 patients with concurrent or previous testicular germ cell tumors; 12 tumors were from metastatic sites and 2 were primary in the testis. Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like). Immunostains directed against INI1, CD57, S-100 protein, NeuN, WT1, neurofilament, CD99, GFAP, synaptophysin, chromogranin, AE1/AE3 cytokeratin, Fli-1 and collagen IV were performed for each case. INI1 was diffusely and strongly positive in all tumors whereas the other stains, except for cytoplasmic WT1 (which showed substantial reactivity in most tumors), were mostly focal to negative, including CD99 (eight negative, six focal) and Fli-1 (all negative). The most consistently reactive 'neuroendocrine' marker was CD57. Each case was also analyzed for chromosome 22 rearrangements using a FISH-based break-apart probe method. Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET. We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs. Future treatment strategies should take these findings into account.

Multifocality in testicular germ cell tumors.

PURPOSE: Standard treatment for testicular germ cell tumor is radical orchiectomy. Several groups have suggested an organ sparing approach in patients with bilateral tumors or tumor in a solitary testis. We determined the prevalence of multifocality in testicular germ cell tumor cases. MATERIALS AND METHODS: Orchiectomy specimens from 145 consecutive patients treated for testicular germ cell tumor between 1995 and 2006 were included in the study. In the current series slides were reviewed by a single dedicated uropathologist. Multifocality was defined as 1 of 4 distinct pathological entities, including 1) distinct tumor focus conspicuously separable from the main tumor mass, 2) microinvasive tumor characterized by a single or small groups of malignant germ cells scattered within the normal interstitial parenchyma, 3) extra tumor vascular invasion and 4) rete testis invasion by pagetoid tumor spread. RESULTS: Multifocality was identified in 48 patients (33%), of whom 17 (12%) had an additional distinct tumor focus, 21 (14%) had microinvasive tumor, 17 had extra tumor vascular invasion and 2 had rete testis invasion by pagetoid tumor spread. Multifocality was more prevalent in men with smaller tumors and seminomatous histology (pure seminoma or as part of a mixed germ cell tumor). Multifocality was present in 63% of men with an index mass of 2 cm or less in diameter. Study limitations include potential pathological sampling errors resulting from the retrospective design. CONCLUSIONS: Multifocality is a frequent finding in testicular germ cell tumor cases that is associated with small mass size and seminomatous histology. Data suggest that additional invasive tumor outside the index mass may be present in up to 63% of men considered potential candidates for organ sparing surgery.

Long-Term Adherence to Medications in Secondary Prevention of Urinary Tract Stones.

Purpose: To reduce the high recurrence rate of nephrolithiasis, patients are routinely prescribed secondary chemoprevention therapy with alkali citrate (Alkasolve®; Sam-On Ltd) for uric acid stones and hypocitraturia or hydrochlorthiazide (Disothiazide®; Dexcel Ltd) for hypercalciuria. However, data on adherence to these regimens are limited. The aim of this study was to assess rates of long-term adherence to alkali citrate and hydrochlorothiazide and reasons for nonadherence. Materials and Methods: Patients on follow-up for kidney stone disease at a dedicated tertiary stone clinic, from 2010 to 2016, were asked to complete a telephone survey on adherence to secondary prevention medications and reasons for nonadherence. Compliance was also verified by actual drug distribution as reported through a computerized monitoring system. Results: The cohort included 356 patients with mean age of 58 years, 199 (64% men, 36% women) treated with alkali citrate and 143 (68% men, 32% women) treated with hydrochlorothiazide. Adherence rates were 42% in the alkali citrate group and 52% in the hydrochlorothiazide group (p = 0.05). The main reason for noncompliance in the alkali citrate group (22%) was the number of pills needed to be taken daily. Adverse drug effects were the most common reason for noncompliance in the hydrochlorothiazide group (24%) and in 10% of the alkali citrate group (p < 0.0005). Adherence was poorer in younger patients who did not regularly take other medications than in older patients with other chronic diseases and polypharmacy. Conclusions: About half the patients with clear metabolic abnormalities who were prescribed secondary chemoprevention with hydrochlorothiazide and alkali citrate failed to adhere to the prescribed regimen. Reasons for noncompliance differed between both drugs. The findings of this study may help clinicians to identify patients at risk for nonadherence and suggests potential means to improve compliance rates.

A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies.

To examine the ability of a new specimen handling technique to improve histopathological yield of ureteroscopic biopsies, performed in patients with suspected upper tract urothelial carcinoma (UTUC). In a bi-center retrospective study we compared the results of the new tissue handling technique (group 1) with the standard technique (group 2). In the new technique, to achieve maximal tissue preservation, the specimen is mounted on filter paper prior to embedding in paraffin. Multivariate analysis was performed to determine which factors are associated with optimal histological results. We further compared the biopsies with the final specimen in a subgroup of patients who underwent nephroureterectomy (NU). Of 55 ureteroscopic biopsies, 1 biopsy from group 1 (new technique) and 3 biopsies from group 2 (standard technique) were inadequate for pathological examination. 51 UTUC specimens were analyzed. Tumor grade and stage were determined in 85% and 63% of the patients in group 1 and in 83% and 25% of group 2 (p=0.85 and p=0.007). Orientation was preserved in 82% of group 1 and 42% of group 2 (p=0.003). On multivariate analysis biopsy technique and biopsy diameter were found to predict stage determination (p=0.01 and p=0.007) and tissue orientation (p=0.005 and p=0.04). Among patients who underwent NU, stage concordance between the biopsy and final pathology was observed in 56% and 27% of the patients in group 1 and 2, respectively. The new processing technique for small UTUC forceps biopsies decreases the rate of biopsies with insufficient material and improves biopsy interpretation.

Transplant Kidney Retrograde Ureteral Stent Placement and Exchange: Overcoming the Challenge.

OBJECTIVE: To present a reliable technique for fluoroscopic controlled, large-bore, ureteral stent placement and exchange in transplant kidneys with persistent ureterovesical strictures. MATERIALS AND METHODS: We reviewed the medical charts of all patients who underwent kidney transplant with persistent ureterovesical strictures who underwent ureteral stent placement or exchange at our institution between 2005 and 2015 using the new technique. Clinical characteristics and treatment outcomes of the study cohort were analyzed. RESULTS: Ureteral stent insertion or stent exchange, using this technique, was performed in 32 renal transplant units. Median operating time was 24 minutes (interquartile range, 21-36.75 minutes). The overall success rate of the technique at first attempt was 96.9%. In 1 patient, drainage of the transplanted kidney with a nephrostomy tube was indicated after procedure failure. No other local or systemic complications were encountered, and no stent encrustation was noted in this cohort of patients. Renal function remained stable in all patients during a median follow-up of 59 months (interquartile range, 28-61 months). CONCLUSION: Herein, we present in detail a step-by-step technique for the insertion and exchange of large-bore ureteral stents in transplanted kidneys. The technique was shown to be safe, effective, and highly successful.

Late relapse of testis cancer.

Most relapses of germ-cell tumors occur within 2 years of initial treatment. In 2% to 4% of patients, relapse may occur later. The retroperitoneum is the primary site of late relapse, and alpha-fetoprotein is the predominant marker. These tumors are highly resistant to chemotherapy. Surgical resection is the preferred treatment. If the recurrent disease is inoperable, chemotherapy may be instituted, followed by resection of residual masses. Patients successfully managed for testis cancer need lifelong surveillance.

Advances in the treatment of testicular cancer.

Germ cell tumors (GCT) are relatively uncommon, accounting for only 1% of male malignancies in the United States. It has become an important oncological disease for several reasons. It is the most common malignancy in young men 15-35 years old. GCTs are among a unique numbers of neoplasms where biochemical markers play a critical role. Finally, it is a model of curable cancer. In this review we discuss cancer epidemiology, genetics, and therapeutic principles. Recent advances in the management of stage I GCT and controversies in the management of post chemotherapy residual mass are presented.

Serum tumor markers in testicular cancer.

Testicular cancer has become a model for a curable neoplasm, where biochemical markers play a critical role. Serum tumor markers are integral in patient management and contributes to the diagnosis, staging, and risk assessment, as well as evaluation of response to therapy and detection of relapse. We review their biochemistry, biology, and clinical use in the setting of localized and metastatic disease. The integration of tumor markers in prognostic models as well as the significance of marker kinetics during chemotherapy is discussed.

Lymphovascular invasion in testicular germ cell tumors: clinicopathological correlates.

INTRODUCTION: We assessed clinical-pathological correlates of lymphovascular invasion in testicular germ-cell tumors. MATERIAL AND METHODS: Archived pathology specimens from 145 patients treated by radical orchiectomy for testicular germ cell tumors at our institution in 1995-2006 were reanalyzed by a dedicated urologic pathologist, and the corresponding medical records were reviewed. The association of lymphovascular invasion with clinical and pathological parameters was tested using stepwise logistic regression analysis. RESULTS: Lymphovascular invasion was identified in 38 (26%) patients and was associated with younger age, testicular pain at presentation, elevated serum tumor markers, nonseminoma histology, and advanced clinical stage. Orchalgia was indicated as the impetus for referral in 67 (46%) patients and characterized as a dull aching sensation, persistent or intermittent in nature. Among the 98 men diagnosed with clinical stage I, those presenting with testicular pain had a 1.8X-higher likelihood of lymphovascular invasion than those without pain (95% CI 1.13-14.9, p = 0.02), and patients with elevated serum tumor markers had an 8.5-fold increased probability of lymphovascular invasion than those presenting with normal tumor markers (CI 1.1-54.2, p = 0.05). Among men with nonseminoma histology, elevated tumor markers was the strongest predictor of lymphovascular invasion in both univariate and multivariate analyses (OR 5.05, 95% CI 1.16-21.8, p = 0.03). CONCLUSION: Providing pathologists with information on pre-orchiectomy tumor marker levels and, possibly, testicular pain at presentation may increase their vigilance in searching for lymphovascular invasion, potentially improving their diagnostic accuracy. Whether it may also translate into improved oncological outcomes needs further evaluation.

Ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux following renal transplantation.

OBJECTIVE: To evaluate the outcome of ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux after renal transplantation. MATERIALS AND METHODS: This is a single-center retrospective review of consecutive patients who underwent ureteropyelostomy after renal transplantation between the years 2000 and 2009. Ureteropyelostomy was performed using the ipsilateral native ureter. The native kidney was not removed. Patients' baseline characteristics, preceding interventions, and postprocedural outcomes were analyzed. RESULTS: Ten patients underwent ureteropyelostomy after renal transplantation. All had initial Lich Gregoir ureterovesical anastomosis. Reasons for the reconstructive surgery were transplant ureteric stenosis in 8 patients or vesicoureteric reflux causing recurrent graft pyelonephritis in 2 patients. Median follow-up was 53 months (range 24-76). Postoperative complications included 3 patients who had transient anastomotic obstruction after removal of the double pigtail stent. They were managed with short-term ureteric restenting or nephrostomy tube insertion. In addition, 2 patients required delayed ipsilateral native nephrectomy because of infection. At last follow-up, all grafts remained unobstructed and free of infections. CONCLUSION: Ureteropyelostomy using the native ureter for the management of transplant ureteric obstruction or symptomatic reflux is safe and provides good long-term preservation of graft function in selected patients.