A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy.

Introduction: Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy. Methods: A multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 µM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients' clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST). Results: The cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4-0.97) and a sensitivity of 96% (24/25, 95% CI 0.80-0.99). Conclusion: EVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors.

Adjuvant chemotherapy after radical cystectomy: Do all patients who need chemotherapy after surgery actually receive it?

Background: Compliance with the guideline recommendations for neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is incomplete. The adjuvant chemotherapy approach has the advantage of pathology-based decision-making, allowing for patient selection. In addition, radical surgery is not delayed and treatment-related toxicity does not impair surgical fitness. The proportion of patients who completed chemotherapy after cystectomy among those who were fit and in need of treatment were evaluated. The reasons for not completing adjuvant chemotherapy were determined. Materials and methods: We retrospectively evaluated all patients who had undergone radical cystectomy at our center over the last 7 years. Indications for adjuvant chemotherapy included pathological T > 2, any node+, or surgical margin involvement. Only patients who were fit for chemotherapy before surgery were included in the study. Results: Of the 52 patients with muscle-invasive bladder cancer, 14 received neoadjuvant chemotherapy or unfit for chemotherapy were excluded. Of the remaining 38 patients, 14 (37%) had bladder-confined cancers and did not require additional chemotherapy. Of the 24 patients who needed chemotherapy and were fit to receive it, 8 patients completed treatment (33%), and 3 discontinued treatment due to toxicity. Twelve patients (50%) declined chemotherapy, whereas 1 patient became unfit for chemotherapy after surgery. Conclusions: While the adjuvant chemotherapy approach could save unnecessary treatment in 37% of patients, two-thirds of those who needed chemotherapy did not complete it. Patient refusal was the primary reason for not receiving treatment.

The Impact of Radiographic, Metabolic and Demographic Characteristics on Kidney Stone Recurrence.

Urolithiasis is a frequent disease with cited rates of recurrence after initial diagnosis that vary widely and range between 35% and 50%. We assessed the radiographic recurrence rate in patients with urinary stones and its risk factors. We retrospectively identified patients who were diagnosed with urinary stones on non-contrast computed tomography from 2010 to 2011, and underwent another imaging examination at least six months afterwards. We collected patient demographic, clinical, laboratory and radiologic data and compared patients with and without urinary stone recurrence. Ultimately, 237 patients were included in the study; the mean follow-up was 6.7 years; 88 patients (37.1%) had recurrence based on our recurrence criteria. On univariate analysis, the significant parameters for recurrence were baseline serum calcium and uric acid, stone location in the kidney, surgical intervention and stone burden volume. On multivariate analysis, surgical intervention (OR 3.07, p = 0.001), baseline calcium (OR 2.56, p = 0.011), baseline uric acid (OR 1.30, p = 0.021) and stone location in the kidney (OR 2.16, p = 0.012) were associated with higher risk of recurrence. These findings may guide personalized follow-up protocols for patients with urolithiasis based on their risk factors.

Fascial dehiscence after radical cystectomy: Is abdominal exploration mandatory?

BACKGROUND: Fascial dehiscence after radical cystectomy may have serious clinical implications. To optimize its management, we sought to describe accompanying intraabdominal findings of post-cystectomy dehiscence repair and determine whether a thorough intraabdominal exploration during its operation is mandatory. METHODS: We retrospectively reviewed a multi-institutional cohort of patients who underwent open radical cystectomy between 2005 and 2020. Patients who underwent exploratory surgery due to fascial dehiscence within 30 days post-cystectomy were included in the analysis. Data collected included demographic characteristics, the clinical presentation of dehiscence, associated laboratory findings, imaging results, surgical parameters, operative findings, and clinical implications. Potential predictors of accompanying intraabdominal complications were investigated. RESULTS: Of 1301 consecutive patients that underwent cystectomy, 27 (2%) had dehiscence repair during a median of 7 days post-surgery. Seven patients (26%) had accompanying intraabdominal pathologies, including urine leaks, a fecal leak, and an internal hernia in 5 (19%), 1 (4%), and 1 (4%) patients, respectively. Accompanying intraabdominal findings were associated with longer hospital stay [20 (IQR 17, 23) vs. 41 (IQR 29, 47) days, P = 0.03] and later dehiscence identification (postoperative day 7 [IQR 5, 9] vs. 10 [IQR 6, 15], P = 0.03). However, the rate of post-exploration complications was similar in both groups. A history of ischemic heart disease was the only predictor for accompanying intraabdominal pathologies (67% vs. 24%; P = 0.02). CONCLUSIONS: A substantial proportion of patients undergoing post-cystectomy fascial dehiscence repair may have unrecognized accompanying surgical complications without prior clinical suspicion. While cardiovascular disease is a risk factor for accompanying findings, meticulous abdominal inspection is imperative in all patients during dehiscence repair. Identification and repair during the surgical intervention may prevent further adverse, possibly life-threatening consequences with minimal risk for iatrogenic injury.

Potential Markers to Reduce Non-Contrast Computed Tomography Use for Symptomatic Patients with Suspected Ureterolithiasis.

Most patients with ureterolithiasis are managed successfully with conservative treatment. In this context, delineation of clinical risk factors that identify patients with low risk for surgical intervention may reduce use of Non-Contrast Computed Tomography (NCCT). Here, emergency department patient files from a 14-month period were reviewed retrospectively, to identify patients who underwent NCCT and showed a ureteral stone. Demographic, clinical and laboratory information was collected. Patients were grouped to either requiring surgical intervention (Group 1) or having successful conservative management (Group 2). The cohort included 368 patients; 36.1% ultimately required surgical intervention (Group 1) and 63.9% were successfully treated conservatively (Group 2). On univariate analysis, patients who required surgical intervention were older, had longer duration of symptoms, had history of urolithiasis and surgical intervention for urolithiasis and had higher serum creatinine levels. Multivariate analysis identified the following risk factors associated with surgical intervention: creatinine >1.5 mg/dL, duration of symptoms ≥ 1.5 days and age > 45 years. Patients with 0, 1, 2 or 3 of the identified risk factors had 19%, 32%, 53% and 73% likelihood, respectively, of surgical intervention. Incorporating these data may reduce the use of NCCT scans in patients who are likely to pass a stone via conservative management.

Drainage of infected kidneys with ureteral stents: does size matter?

PURPOSE: The purpose of our study was to evaluate the ability of ureteral stents with different diameters to drain pus that accumulates in an obstructed kidney using an in vitro model. METHODS: We developed an in vitro model of an obstructed kidney filled with pus. The model included a silicon kidney unit based on computed tomography (CT) data, a 3D printed ureteral stone based on a real extracted ureteral stone, a latex ureter model, a bladder vessel, and a fluid with qualities resembling pus. Identical printed stones were inserted into four ureter models containing stents with varying diameters (4.8F, 6F, 7F, 8F), each of which was connected to the kidney unit and the bladder vessel. The kidney unit was filled with artificial pus to pressures of 30 cmH2O to simulate an infected and obstructed kidney. The obstruction was relieved with stents in place, while artificial urine was pumped into the kidney; pressure in the kidney and remaining pus were measured continuously. RESULTS: The rate of pressure drop and the final pressure measured in the kidney were unaffected by the diameter of the stent. For all stent diameters, the pressure reached non-obstructed levels within 30 s, final pressure was reached within 90-120 s, and minimal amounts of pus remained in the kidney after 120 min. CONCLUSIONS: In vitro experiments demonstrate that all stent diameters drain pus-filled, obstructed kidneys with the same efficacy. The common perception that larger diameter tubes are more effective under such circumstances should be re-examined.

When should we give up on expectant management for patients with proximal ureteral stones?

Background: Proximal ureteral stones (PUS) have relatively low rates of spontaneous expulsion. However, some patients do well on expectant management. Our aim was to compare risk factors for surgical intervention in patients with PUS who underwent primary intervention to those subjected to expectant management. Materials and methods: We retrospectively reviewed the medical charts of patients presented to the emergency room with symptoms of renal colic and underwent computerized tomography between August 2016 and August 2017. A total of 97 consecutive patients were identified with up to 10mm PUS. We collected patient demographics, clinical, and imaging data, and performed binary regression analysis for risk of intervention. Results: The average age was 49years (range 17-97) and average stone size was 7.1mm (range 3-10). Forty-one patients underwent immediate intervention while the remaining 56 patients were treated conservatively. Of the 56 patients treated conservatively, 26 underwent delayed intervention while 30 reported spontaneous stone expulsion. On univariate analysis of all 97 patients, statistically significant risk factors for intervention were found based on stone size, age, serum lymphocyte, platelet counts, and stone density. Of these risk factors, stone size ≥ 7mm (p = 0.012, odds ratio = 5.4) and platelet count ≤ 230K/µL (p = 0.027, odds ratio = 4.9) remained statistically significant on multivariate analysis. Conclusion: Stone size and platelet count were found to be risk factors for surgical intervention in patients with up to 10mm PUS. These findings may assist in identifying patients who are more suitable for conservative approach.

Surgical Outcomes in High-risk Prostate Cancer and Salvage Radical Prostatectomy.

BACKGROUND: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered. OBJECTIVES: To describe our experience with surgery of high-risk patients and SRP. METHODS: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes. RESULTS: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed. CONCLUSIONS: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.

Radical Cystectomy after Previous Radiation or Pelvic Surgery: Is It Associated with Increased Morbidity?

BACKGROUND: Radical cystectomy is a complicated surgery with significant risks. Complications of Clavien-Dindo grade 3-4 range from 25% to 40% while risk of mortality is 2%. Pelvic surgery or radiotherapy prior to radical cystectomy increases the challenges of this surgery. OBJECTIVES: To assess whether radical cystectomy performed in patients with prior history of pelvic surgery or radiation was associated with increased frequency of Clavien-Dindo grade 3 or higher complications compared to patients without prior pelvic intervention. METHODS: We retrospectively evaluated all patients who underwent radical cystectomy at our center over a 7-year period. All patients with pelvic radiation or surgery prior to radical cystectomy comprised group 1, while group 2 included the remaining patients. RESULTS: In our study, 65 patients required radical cystectomy at our institution during the study period. Group 1 was comprised of 17 patients and group 2 included 48 patients. Four patients from group 2 received orthotopic neobladder, while an ileal conduit procedure was performed in the remaining patients. Estimated blood loss and the amount of blood transfusions given was the only variable found to be statistically different between the two groups. One patient from group 1 had four pelvic interventions prior to surgery, and her cystectomy was aborted. CONCLUSIONS: Radical cystectomy may be safely performed in patients with a history of pelvic radiotherapy or surgery, with complication rates similar to those of non-irradiated or operated pelvises.

Comparative study of renal drainage with different ureteral stents subject to extrinsic ureteral obstruction using an in vitro ureter-stent model.

BACKGROUND: To compare the efficacy of different ureteral stents subject to extrinsic ureteral obstruction (EUO), in a controlled in vitro stented ureter experiment. METHODS: We employ an in vitro ureter-stent experimental set-up, with latex tubing simulating flexible ureters attached to vessels simulating renal units and bladders. The flow behavior of five ureteral stents-polymeric 8F, tandem 6F, tandem 7F, endopyelotomy and metal-was tested under a ureteral deformation configuration of 40°, with 2000 g external force over a 3.5 cm length of the ureter. A constant fluid flow was applied through the ureter-stent configurations, and pressure fluctuations in the renal unit were monitored. We considered a renal unit pressure of 10 cmH2O or flow discontinuation in the bladder as stent failure. Urine containing debris was mimicked by use of a colloidal solution. RESULTS: Of all assessed ureteral stents, under EUO conditions, only the single 8F stents remained patent throughout the length of the experiment. All other stents-tandem 6F and 7F, single 7F, metal and endopyelotomy-displayed limitations. CONCLUSIONS: Tandem and metal stents show no superiority over large luminal polymeric stents for EUO treatment in this in vitro model. Larger luminal stents offer excellent resistance to external pressure and allow adequate colloidal flow. The need for frequent exchange and bladder irritation should also be considered in the choice of stent configuration for treatment of kidney drainage under EUO.

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.

Do organic substances act as a degradable binding matrix in calcium oxalate kidney stones?

BACKGROUND: Calcium oxalate (CaOx) stones are considered to be highly resistant to chemolysis. While significant organic matter has been identified within these stones, which is presumed to bind (inorganic) CaOx particles and aggregates, most chemolysis efforts have focused on methods to attack the CaOx components of a stone. We examine the feasibility of inducing chemolysis of CaOx kidney stones, within hours, by specifically attacking the organic matrix present in these stones. METHODS: In contrast to previous studies, we focused on the possible "brick and mortar" stone configuration. We systematically tested, via in vitro experiments, the ability of an extensive range of 26 potential chemolysis agents to induce relatively fast disintegration (and/or dissolution) of a large set of natural CaOx stone fragments, extracted during endourological procedures, without regard to immediate clinical application. Each stone fragment was monitored for reduction in weight and other changes over 72 h. RESULTS: We find that agents known to attack organic material have little, if any, effect on stone chemolysis. Similarly, protein and enzymatic agents, and oral additive medical treatments, have little immediate effect. CONCLUSIONS: These findings suggest that the organic and inorganic constituents present in CaOx stones are not structured as "brick and mortar" configurations in terms of inorganic and organic components.

Do patients with ureterolithiasis treated conservatively return to follow up?

INTRODUCTION Distal ureteral stones (DUS) are common in patients presenting to the emergency department (ED) with renal colic. The majority of DUS will pass spontaneously and therefore conservative care is common. Follow up is imperative as some of these stones might not pass and potentially lead to complications. The aim of our study was to evaluate the rate of compliance with follow up and to find predictive variables for it. MATERIALS AND METHODS: We retrospectively surveyed the medical records of all patients who had a non-contrast computed tomography (NCCT) at our ED between 01/03/16 and 31/5/17. We included patients with a DUS smaller than 10 mm that were treated conservatively. We obtained demographic, clinical, laboratory and imaging data. Compliance to follow up was evaluated by surveying the medical records and by calling the patients. We then compared the characteristics of patients who returned for follow up to those who did not. RESULTS: A total of 230 consecutive patients were included in our cohort: 194 (84%) patients were male and the average age was 46 y (21-82); 138 patients (60%) returned for a follow up visit while 92 patients (40%) did not. Univariate analysis revealed stone size and admission to hospital to be predictive of compliance to follow up while multivariate analysis revealed only hospital admission to be predictive of compliance. CONCLUSIONS: Only 60% of the patients with DUS treated conservatively return for a follow up visit. Hospital admission, which likely reflects appropriate patients counseling by a urologist and adequate follow up scheduling, was found to be associated with increased compliance with follow up.

Single Instillation of Hypertonic Saline Immediately Following Transurethral Resection of Bladder Tumor for Recurrence Prevention -A Phase I Study.

BACKGROUND: Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. OBJECTIVE: To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. METHODS: In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12-24 hours after instillation. Adverse effects were documented and compared between the groups. RESULTS: In rats, average sodium levels were 140.0 mEq/L and 140.3 mEq/L before and following instillation, respectively. Necropsy revealed no signs of inflammation or blue discoloration. In humans the average plasma sodium levels were 138.6 mEq∖L, 138.8 mEq∖L and 137.7 mEq∖L before, 1 hour and 12-24 hours after instillation, respectively. During the postoperative follow-up there was one case of fever. A month after the surgery, dysuria was reported by 5 patients while urgency and hematuria were reported by one patient each. The most severe adverse events were grade 2 on the Clavien-Dindo scale. Adverse events were similar in the control group. CONCLUSIONS: Hypersal instillation is safe and tolerable immediately after TURBT.

Impact of Colloidal Fluid on Stent Failure Under Extrinsic Ureteral Obstruction: An In Vitro Experimental Study.

Background and Purpose: Drainage of an obstructed kidney due to extrinsic ureteral obstruction (EUO) is imperative. Ureteral stents, commonly employed to facilitate drainage, often fail under EUO; this is usually attributed to external pressure over the ureter that occludes the stent lumen. We showed previously that external pressure and deformation of the ureter, alone, cannot explain frequent stent failure and speculated that colloids present in urine may play a critical synergetic role. In this study, we evaluate the role of colloidal fluid in ureteral obstruction under extrinsic compression. Materials and Methods: An in vitro ureter-stent model was employed using a latex tube to simulate a flexible ureter connecting simulated glass kidney and bladder units. The ureter was placed in deformed configuration of 40° with external pressure of 2000 g exerted over the deformed region of the stented ureter, representing extrinsic pressure. Four different ureteral stents were tested-4.8F, 6F, 7F, and 8F. Colloidal solution based on chicken albumin was injected through the simulated kidney into the stented ureter. Four replicates were performed for each stent diameter and straight stented ureters with no external pressure were used as controls. Stent failure was defined as kidney unit pressure over 10 cmH2O or complete obstruction of fluid flow; time to stent failure was measured. Results: Average failure time in 4.8F and 6F stents was 44 and 66 hours, respectively. The 7F ureteral stent failed in two replicates, after an average time of 75 hours, and continued to drain in the other two replicates. The 8F and control stents showed no change in kidney unit pressure in any of the replicates. Conclusions: Large-diameter stents are more effective in ureteral drainage under EUO in the presence of colloidal material in the fluid. Colloidal fluid may have a role in stent failure under EUO.

The Impact of Ureteral Deformation and External Ureteral Pressure on Stent Failure in Extrinsic Ureteral Obstruction: An In Vitro Experimental Study.

Background and Purpose: Extrinsic ureteral obstruction is caused frequently by pelvic malignancies or metastatic lymphadenopathy, necessitating renal drainage with ureteral stents to prevent renal failure and kidney damage. Understanding the nature of stent behavior under deformation and realistic external pressures may assist in evaluation of stent performance. Few published studies have investigated the flow and mechanical properties of stents within ureters, and none has considered the effects of deformation and compression on flow in realistic, in vitro, ureter-stent systems. The purpose of this work was to determine whether or not stent failure is due only to stent compression and deformation in the presence of extrinsic obstruction. Methods: We developed an in vitro ureter-stent experimental setup, using latex tubing to simulate a flexible ureter connecting a renal unit and a bladder side. We examined flow behavior in three stents (4.8F, 6F, 7F). The ureter-stent configuration was varied, simulating four levels of deformation (0°, 20°, 40°, 60°) and then simulating different external compressive forces on a stented ureter with 40° deformation. A constant, realistic fluid flow was applied through the ureter-stent configurations, and pressure fluctuations in the renal unit were monitored. Results: Deformation alone on four different levels (0°, 20°, 40°, 60°) has essentially no influence on fluid flow and renal pressure variation. Under increasing external compressive forces of 500, 1000, 2000, and up to 5000 g at 40° deformation, no effect on fluid flow and pressure within the renal unit was noted for the 6F and 7F stents. The only exception was for the 4.8F stent, which demonstrated complete failure at compressive forces near 4000 g. Conclusions: Neither realistic extrinsic ureteral compression forces nor ureteral deformation explain the high frequency of stent failure in extrinsic ureteral obstruction. Other factors such as urine composition may be a major contributor to stent failure.

Prediction of Surgical Intervention for Distal Ureteral Stones.

Introduction and Objective: Eighty percent of patients with distal ureteral stones <10 mm will ultimately pass the stone under conservative care. Nonetheless, some may experience related morbidity before surgical intervention is performed. Our study aims to find predictive variables for surgical intervention. Methods: We retrospectively surveyed medical records of patients found to have distal ureteral stone up to 10 mm by noncontrast computed tomography (NCCT) done between March 1, 2016 and May 31, 2017. Demographic, clinical, laboratory, and radiologic data were obtained. We compared characteristics of patients who underwent surgical intervention (ureteroscopy/renal drainage) with those treated conservatively. Results: A total of 268 consecutive patients were included: 226 (84%) were male and the average age was 46 years (18-82). Of these patients, 60 patients (22%) underwent surgical intervention (group 1) and 208 patients (78%) were treated expectantly (group 2). No significant differences were observed with respect to demographic data or proportion of patients treated with medical expulsive therapy between the groups. Univariate analysis found stone diameter, stone-to-ureterovesical junction (UVJ) distance, stone density, presence of a "rim sign" on NCCT, and pain duration at presentation to be significantly different between the groups. Multivariate analysis showed stone diameter, stone-to-UVJ distance, and pain duration at presentation to be independently predictive for intervention. Receiver operating characteristics curve analysis identified stone size >4 mm, stone-to-UVJ distance >4 mm, and pain duration >4 days to be the most significant cutoff points for patient risk stratification-"Rule of 4's." Further analysis showed that the prevalence of intervention among patients with 0, 1, 2, and 3 risk factors was 4.3%, 22.1%, 45%, and 66.7%, respectively. Conclusions: Stone size, stone distance from the UVJ, and pain duration play a significant role in predicting surgical intervention. "Rule of 4's" may aid in early recognition of patients who will ultimately undergo intervention and omit the burden of nonfavorable expectant management.

Spermatogenesis in Testicles with Germ Cell Tumors.

BACKGROUND: Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear. OBJECTIVES: To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT. METHODS: We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann-Whitney was applied to determine the correlation between MTD and IF. RESULTS: Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF. CONCLUSIONS: IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.