Natural history and health care burden of non-curative treatment for muscle-invasive bladder cancer.

OBJECTIVE: Muscle-invasive bladder cancer is an aggressive disease. Yet, many patients, especially those with advanced age and multiple comorbidities, do not receive treatment with curative intent. We evaluated the disease course and health care burden of these patients. MATERIALS AND METHODS: Bi-center, retrospective analysis of patients diagnosed with muscle-invasive bladder cancer who did not undergo curative-intent treatment (radical cystectomy or trimodal therapy) between 2016 and 2021. Patient characteristics and treatment burden were described. Metastasis-free, cancer-specific, and overall survivals were evaluated using the Kaplan-Meier method. RESULTS: Sixty-six patients with a median age of 86 (IQR 78,90) were evaluated. The median follow-up for survivors was 29 months (IQR 9, 44). All patients were diagnosed with muscle-invasive bladder cancer, and 32 (48%) presented with clinical T3 and T4 disease. The median age adjusted Charlson comorbidity index at diagnosis was 7 (IQR 6,8). Treatment with curative intent was not provided due to comorbidities and low-performance status in 58 patients (88%) and patient refusal in 8 (12%). Two-year estimated metastasis-free survival, cancer-specific survival, and overall survival were 11%, 18%, and 12%, respectively. During follow-up, 7 patients (10%) were treated with chemotherapy, 4 (6%) received immunotherapy, 21 (32%) radiation, and 17 (26%) had emergent operations due to hematuria. Twenty-four patients (37%) required nephrostomy tubes, and 39 (59%) required an indwelling urinary catheter for various periods. Forty-three patients (65%) suffered from recurrent hematuria episodes. Overall, median emergency room visits were 4 (IQR 2, 6), and median hospital admission was 16 days (IQR 9, 29). CONCLUSIONS: Untreated muscle-invasive bladder cancer is associated with a limited lifespan and a high disease burden for the patient and health system. These data should be taken into consideration and portrayed to the patient when curative intent treatment is chosen to be avoided.

Sterile Water Versus Glycine in Transurethral Resection of Bladder Tumors-Immunogenic and Clinical Implications.

BACKGROUND AND OBJECTIVE: We compared the oncologic outcomes of patients with non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TUBRT) using sterile water vs glycine irrigation. The tumoricidal and immunogenic effects of these solutions on urothelial cancer cell lines were investigated. METHODS: The medical records of 530 consecutive patients who underwent TURBT using sterile water or glycine irrigation for NMIBC were reviewed. Recurrence and progression rates were evaluated using time dependent analyses.Bladder cancer cell lines (RT4, T24 and 5637) were treated with glycine and sterile water. Cell viability was evaluated with the XTT assay. Cell membrane calreticulin levels were evaluated with flow cytometry. Extracellular high mobility group box 1 (HMGB1) and heat shock 70 (HSP70) protein levels were evaluated using western blots. KEY FINDINGS AND LIMITATIONS: After propensity score matching each study arm comprised 161 patients. Median follow-up was 13.6 months (IQR 6.2, 24.5). The 2-year recurrence free survival was significantly lower in the sterile water vs glycine group (43% vs 71%, respectively, p<0.0001). Similarly, the 2-years progression free survival was significantly lower in the sterile water vs glycine group (85% vs 94%, respectively, p<0.014). Sterile water treatment resulted in the lowest number of viable cells. Early and late immunogenic cell death markers were markedly elevated in cells treated with glycine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Sterile water compared to glycine irrigation during TURBT for NMIBC was associated with higher recurrence and progression rates. Possible explanation for these findings is the diminished immune response associated with sterile water reflected in a comparatively lesser expression of immune response inducers. PATIENT SUMMARY: We compared two irrigation fluids in non-muscle-invasive bladder cancer surgery: glycine and sterile water. Glycine outperformed sterile water in cancer recurrence, possibly boosting immunogenicity over sterile water.

Revisiting the issue of "beach balls" in holmium laser enucleation of prostate: clinical and histological characterization.

PURPOSE: To clinically and histologically characterize prostatic nodules resistant to morcellation ("beach balls," BBs). PATIENTS AND METHODS: We reviewed a consecutive cohort of 559 holmium laser enucleation of the prostate (HoLEP) procedures performed between January 2020 and November 2023. The BBs group comprised 55 men (10%) and the control group comprised 504 men (90%). The clinical, intraoperative, outcome, and histologic data were statistically processed for the prediction of the presence of BBs and their influence on the perioperative course and outcome. RESULTS: The BBs group in comparison to the controls was older (75 vs 73 years, respectively, p = 0.009) and had higher rates of chronic retention (51 vs 29%, p = 0.001), larger prostates on preoperative abdominal ultrasound (AUS) (140 vs 80 cc, p = 0.006E-16), longer operating time (120 vs 80 min, p = 0.001), higher weights of removed tissue (101 vs 60 gr, p = 0.008E-10), higher complication rates (5 vs 1%, p = 0.03), and longer hospitalization (p = 0.014). A multivariate analysis revealed that larger prostates on preoperative AUS and older age independently predicted the presence of BBs which would prolong operating time. ROC analyses revealed that a threshold of 103 cc on AUS predicted BBs with 94% sensitivity and 84% specificity. BBs were mostly characterized histologically by stromal component (p = 0.005). CONCLUSIONS: BBs are expected in older patients and cases of chronic retention. Prostatic volume is the most reliable predictor of their presence. They contribute to prolonged operating time and increased risk of complications. The predominantly stromal composition of the BBs apparently confers their resistance to morcellation.

Megameatus intact prepuce variant reconstruction: Long-term outcomes and comparison to post-circumcision hypospadias repair.

BACKGROUND: Megameatus intact prepuce (MIP) variant is considered a surgical challenge with associated high complication rates. It is usually diagnosed and corrected only after neonatal circumcision, which is discouraged in non-MIP hypospadias. OBJECTIVE: In order to determine whether the features of the MIP variant or the performance of a secondary reconstruction following circumcision comprise the cause of higher complication rates, we now compared the results of post-circumcision MIP hypospadias repair to the results of children who underwent repair of non-MIP hypospadias following neonatal circumcision. STUDY DESIGN: Reoperation rates of children operated for hypospadias repair following neonatal circumcision between 1999 and 2020 were compared between those with MIP and those with classic non-MIP hypospadias. RESULTS: In total, 139 patients who had undergone neonatal circumcision underwent surgical reconstruction at a mean age of 13 months. Sixty-nine had classic hypospadias and 70 had the MIP variant. The median follow-up was 10 years (interquartile range 6,13). The classic group had a higher rate of meatal location below the corona compared to the MIP variant group (53 % vs. 28 %, respectively, p = 0.002). The reoperation rate was comparable for the two groups (32 % vs. 27 %, p = 0.58, Table). Univariate analysis for the MIP hypospadias group showed no association between reoperation and the initial patient characteristics, while a higher probability of reoperation was demonstrated in the presence of ventral curvature (odds ratio 3.5, p = 0.02), and a higher grade of hypospadias (odds ratio 3.3, p = 0.03 for meatal location lower than the coronal sulcus) in the non-MIP group. DISCUSSION: The limitations of our work include its retrospective design wherein the patients' characteristics, including classification as MIP vs. non-MIP, are derived from medical records. More patients in the non-MIP group were documented to have penile curvature. The non-MIP group was composed of more patients with meatal location under the coronal sulcus, a factor which may increase the rates for reoperation in that group. Still, with the comparison of the largest reported cohort of circumcised MIP with circumcised non-MIP patients together with an extended follow-up period, we believe that we present strong evidence of the possible role of previous circumcision in the surgical challenge of reconstructing MIP hypospadias. CONCLUSIONS: Reoperation rates in MIP hypospadias are high but similar to those of classic hypospadias, both following circumcision, suggesting that circumcision, rather than the unique features of the variant, is the cause for complications.

Assessment of Intra-Abdominal Pressure with a Novel Continuous Bladder Pressure Monitor-A Clinical Validation Study.

INTRODUCTION: Intra-abdominal hypertension and the resulting abdominal compartment syndrome are serious complications of severely ill patients. Diagnosis requires an intra-abdominal pressure (IAP) measurement, which is currently cumbersome and underused. We aimed to test the accuracy of a novel continuous IAP monitor. METHODS: Adults having laparoscopic surgery and requiring urinary catheter intra-operatively were recruited to this single-arm validation study. IAP measurements using the novel monitor and a gold-standard foley manometer were compared. After anesthesia induction, a pneumoperitoneum was induced through a laparoscopic insufflator, and five randomly pre-defined pressures (between 5 and 25 mmHg) were achieved and simultaneously measured via both methods in each participant. Measurements were compared using Bland-Altman analysis. RESULTS: In total, 29 participants completed the study and provided 144 distinct pairs of pressure measurements that were analyzed. A positive correlation between the two methods was found (R2 = 0.93). There was good agreement between the methods, with a mean bias (95% CI) of -0.4 (-0.6, -0.1) mmHg and a standard deviation of 1.3 mmHg, which was statistically significant but of no clinical importance. The limits of agreement (where 95% of the differences are expected to fall) were -2.9 and 2.2 mmHg. The proportional error was statistically insignificant (p = 0.85), suggesting a constant agreement between the methods across the range of values tested. The percentage error was 10.7%. CONCLUSIONS: Continuous IAP measurements using the novel monitor performed well in the clinical setup of controlled intra-abdominal hypertension across the evaluated range of pressures. Further studies should expand the range to more pathological values.

Operative techniques and long-term outcomes of hypospadias repair in the absence of preputial skin after neonatal circumcision.

PURPOSE: To present the results of hypospadias repair in the absence of preputial skin following neonatal circumcision, and the analyses of surgical techniques and predictors of procedural success. METHODS: Records of all children who underwent hypospadias repair between 10/1999 and 12/2018 were retrospectively reviewed. All of those who underwent neonatal circumcision prior to surgery were included. Patients with any prior penile reconstruction surgery and those with the megameatus intact prepuce variant were excluded. The primary endpoint was the need for reoperation. RESULTS: A total of 69 patients with a history of neonatal circumcision underwent surgical reconstruction of hypospadias during the study period. Their mean age at surgery was 14 months (interquartile range [IQR] 9,22). Forty-five cases (65%) involved distal hypospadias, and ventral curvature was present in 24 (35%). Dartos flaps were harvested from the dorsal aspect in 37/58 (64%) patients and from the ventral aspect in 21/58 (36%). Twenty-two patients (22/69, 32%) required reoperation after a median follow-up of 9 years (IQR 6,13). Indications for revision surgery included urethral fistula (n = 16, 22%), meatal stenosis (n = 5, 7%), and skin redundancy (n = 1). Ventral curvature (odds ratio [OR] 3.5, p = 0.02) and higher grades of hypospadias. (OR 3.3, p = 0.03) had a higher probability of reoperation (univariate logistic regression). CONCLUSION: Hypospadias repair following neonatal circumcision in the absence of preputial skin is a challenging reconstruction. The reoperation rate in our cohort was 30%, similar to reoperative hypospadias surgery. Parents of newborns diagnosed with hypospadias should be encouraged to refrain from pre surgical neonatal circumcision. LEVEL OF EVIDENCE: Treatment study, level IV.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Querying the significance of patient position during computerized tomography on the reliability of pre-percutaneous nephrolithotomy planning.

BACKGROUND: Computerized tomography (CT) is considered indispensable in percutaneous nephrolithotomy (PCNL) planning. We aimed to define the reliability of pre-PCNL CT for planning renal access by assessing renal positional changes between supine and prone CTs. SUBJECTS AND METHODS: CT urographies (CTU) of 30 consecutive patients were reviewed for distances upper pole (UP)-diaphragm, UP-diaphragm attachment, renal pelvis (RP)-lateral body wall, RP- posterior body wall, and lower pole (LP)- anterior-superior iliac spine (ASIS). The posterior and lateral renal axes angles were also calculated. RESULTS: The most consistent overall movement in transition from prone to supine was backward rotation, as demonstrated by a decrease in distance UP-posterior body wall (p = 0.010) and increase in the posterior renal angle (p < 0.0001). This finding correlated with the patient's body mass index (BMI) (p = 0.029). The left kidney was more mobile than the right one, moving significantly for five of the measured parameters compared to the right kidney which moved significantly for only two parameters. The UP-diaphragm distance of the left kidney correlated with age (p = 0.014), the RP-lateral wall distance correlated with previous abdominal surgery (p = 0.006), and the RP-posterior wall distance with BMI (p = 0.017). On the right, the UP-diaphragm distance correlated with gender (p = 0.002) and the lateral renal rotation was smaller (p = 0.046). CONCLUSIONS: Kidneys present significant mobility between supine and prone positions. CT assessment should be performed in the position expected during surgery and should be interpreted with caution, while a real-time imaging modality should be used in the operating room.

Dorsal penile curvature and megameatus intact prepuce hypospadias: A common association in a rare variant of hypospadias.

BACKGROUND: Megameatus intact prepuce (MIP) is a rare variant of hypospadias. Unlike the hooded ventrally absent prepuce in non-MIP hypospadias, the prepuce in MIP hypospadias is fully circumferential and intact. The distal urethra remains wide with a deep glanular groove. While ventral curvature is a common finding in non-MIP hypospadias, neither ventral nor dorsal penile curvature has been reported in MIP hypospadias. OBJECTIVE: To assess the association of the MIP hypospadias variant with penile curvature. STUDY DESIGN: We retrospectively reviewed the medical records of all children who underwent hypospadias repair and identified those who were documented as having the MIP variant of hypospadias and operated in our center from January 1998 to June 2020. The patients were considered as having MIP hypospadias if no hypospadias had been evident before circumcision, if a circumferential circumcision scar was present (instead of the inverted V-shaped scar in the ventral aspect of the penis following circumcision of the hooded prepuce associated with non-MIP hypospadias), and if there was a wide meatus. Penile curvature was diagnosed intraoperatively by an artificial erection test that uses saline solution for injection. Patients were considered surgical candidates if the degree of curvature was equal to or greater than 30°. RESULTS: The study cohort consisted of 118 male children who were identified as having the MIP hypospadias variant according to the inclusion criteria. The median age at repair was 1.1 years (interquartile range 8 months to 1.6 years). Penile curvature was found in 29 children (24%), of whom 23 had dorsal curvatures (19%) and 6 had ventral curvatures (5%). DISCUSSION: MIP hypospadias is associated with penile curvature, and more frequently with dorsal than ventral curvature. This study is retrospective and does now identify specific features of MIP associated with penile curvature. We encourage pediatric urologists to perform an artificial erection test intraoperatively in children with the MIP variant and repair associated curvatures. CONCLUSIONS: A dorsal curvature was found in 19% of patients with a MIP variant of hypospadias, and most of them (86%) required ventral plication due to the severity of the curvature.

Radical cystectomy and perioperative chemotherapy in octogenarians with bladder cancer.

INTRODUCTION: We aimed to compare the treatment patterns and oncological outcomes, including postoperative morbidity and chemotherapy use, between octogenarians and patients <80 years of age who underwent radical cystectomy for bladder cancer. METHODS: We conducted a retrospective analysis of 119 patients who underwent radical cystectomy for bladder cancer at our center between January 2013 and April 2019. Comorbidities, clinical and pathological data, 30-day postoperative morbidity, and perioperative chemotherapy use were compared between octogenarians (n=31) and younger patients (n=88). Cancer-specific and overall survival rates were estimated with the Kaplan-Meier method and compared between the groups. RESULTS: No significant differences were found between the age groups in the clinical and pathological findings, including Charlson comorbidity index, modified frailty index, albumin level, renal function, and TNM stage. The median followup for survivors was 19 months (interquartile range [IQR] 11-30). Major complications (Clavien-Dindo grade ≥3) and 30-day postoperative mortality rates did not differ between the age groups (p=0.3 and p=0.18, respectively). Despite no difference in baseline glomerular filtration rates, perioperative chemotherapy utilization rate was lower among octogenarians compared to younger patients (13% vs. 34%, p=0.03). Estimated two-year cancer-specific survival rates for octo-generians and younger patients were 40% and 75%, respectively. Similarly, estimated two-year overall survival rates were 30% and 69%, respectively. Both cancer-specific and overall survival rates were significantly lower in octogenarians (p=0.007 and p=0.001, respectively). CONCLUSIONS: Radical cystectomy in octogenarians results in comparable short-term outcomes as in younger patients. However, in the elderly population, perioperative chemotherapy utilization rates are lower and survival is inferior.

Long-Term Follow-Up of Yearly Replaced Double Internal Stents for Extrinsic Malignant Ureteral Obstruction.

Introduction: To assess long-term outcomes of double internal stents (DIS) for the relief of external malignant ureteral obstruction (MUO). Materials and Methods: DIS (7F each; 12-month indwelling time) were inserted under general anesthesia in 62 consecutive patients (75 renal units) with MUO during 2007-2018. Surveillance was performed every 3 months, and stents were exchanged routinely every year. The need for permanent stent retrieval was considered stent failure. Maintenance of stent patency and disease-specific survival (DSS) were estimated (Kaplan-Meier). Risk factors were also assessed (univariate and multivariable Cox regression analyses). Results: The median follow-up was 27 months (interquartile range [IQR] 20-27). The most frequent tumors causing obstruction were colorectal and ovarian cancers. Six patients (10%) had stent failure caused by sepsis, creatinine elevation, or hematuria. The average time to failure was 15 months (range 1-27). A history of radiation and an estimated glomerular filtration rate (eGFR) ≤45 mL/(min/1.73 m2) were associated with stent failure (p = 0.038 and p = 0.001, respectively). Thirty-nine patients died with a median DSS of 21 months (IQR 8.6-not reached). Multivariate analysis identified eGFR ≤60 mL/(min/1.73 m2) (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1-4.2, p = 0.02) and need for balloon dilation (HR 2.1, 95% CI 1.1-4.1, p = 0.02) as independent predictors for disease-related mortality. Twenty-six patients (42%) had stent-related complications, for example, irritative symptoms, hematuria, and infections, of whom only two failed. Conclusions: One-year indwelling DIS provide effective long-term relief of MUO and represent a simple and effective alternative to other methods of urinary diversion. They avoid the need for external tubes and contribute to improved patient satisfaction.

Is it safe to use a ureteral access sheath in an unstented ureter?

BACKGROUND: The aim of this study was to examine ureteral stricture rate after the use of UAS in an unstented ureter and compare complications of smaller vs. larger-caliber UAS. METHODS: We conducted a retrospective analysis of consecutive RIRS for renal stones, with the use of UAS in unstented ureters. We excluded cases with previous ureteroscopies, who carried ureteral stent or nephrostomy, had impacted stones, underwent radiation treatment, or had urinary tract malignancies. The primary outcome was formation of ureteral strictures diagnosed by hydronephrosis in ultrasound test and late secretion in dynamic renal scan. Secondary outcome was stone-free-rate (SFR) and complications. In addition, we compared safety and efficacy of smaller (9.5/11.5Fr) vs. larger-caliber (12/14Fr) UAS. RESULTS: The cohort included 165 patients with a median follow-up time of 115 days. There was no case of ureteral stricture formation after the use us UAS, despite using a larger-caliber UAS in nearly half the cases. Larger-caliber UAS was not associated with more complications compared to the smaller-caliber one (p = 0.780). SFR was non-significantly higher in the larger-caliber UAS group (p = 0.056), despite having a larger stone burden, and only stone number was associated with SFR (p = 0.003). CONCLUSIONS: These data suggest that the use of UAS during RIRS in an unstented ureter is safe and does not involve ureteral stricture formation after one procedure. Furthermore, the use of wider sheaths was not found to be associated with higher complications rate.