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.

A combined MRI-PSAD risk stratification system for prioritizing prostate biopsies.

INTRODUCTION:   Prostate cancer screening with PSA is associated with low specificity; furthermore, little is known about the optimal timing of biopsy.  We aimed to evaluate whether a risk classification system combining PSA density (PSAD) and mpMRI can predict clinically significant cancer and determine biopsy timing. MATERIALS AND METHODS:  We reviewed the medical records of 256 men with a PI-RADS ≥ 3 lesion on mpMRI who underwent transperineal targeted and systematic biopsies of the prostate between 2017-2019.  Patients were stratified into three risk groups based on PSAD and mpMRI findings. The study endpoint was clinically significant prostate cancer (CSPC).  The association between the risk groups and CSPC was evaluated. RESULTS:  Based on the proposed risk stratification system 42/256 men (16%) were high-risk (mpMRI finding of extra-prostatic extension and/or seminal vesicle invasion and/or a PI-RADS 5 lesion with a PSAD > 0.15 ng/mL²), 164/256 (64%) intermediate-risk (PI-RADS 4-5 lesions and/or PSAD > 0.15ng/mL² with no high-risk features) and 50/256 (20%) low-risk (PI-RADS 3 lesions and PSAD ≤ 0.15 ng/mL²).  High-risk patients had significantly higher rates of CSPC (76%) when compared to intermediate-risk (26%) and low-risk (4%).  On multivariable logistic regression analysis adjusted for age, previous biopsy, and clinical T-stage we found an association between intermediate-risk (OR = 4.84, p = 0.038) and high-risk (OR = 40.13, p < 0.001) features and CSPC.  High-risk patients had a shorter median biopsy delay time (110 days) compared to intermediate- and low-risk patients (141 and 147 days, respectively).  We did not find an association between biopsy delay and CSPC. CONCLUSIONS:   Our findings suggest that a three-tier risk classification system based on mpMRI and PSAD can identify patients at high-risk for CSPC who may benefit from earlier biopsy.

Assessing the Impact of Percutaneous Nephrostomy Presence on Neoadjuvant Treatment Quality in Patients With Muscle Invasive Bladder Cancer.

INTRODUCTION: Symptomatic hydronephrosis associated with muscle invasive bladder cancer (MIBC) necessitates percutaneous nephrostomy (PCN) insertion before neoadjuvant chemotherapy (NAC). This study assesses the impact of PCN presence on standard intended NAC quality, its related complications and outcome after radical cystectomy (RC). MATERIALS AND METHODS: The study comprises a retrospective, multicenter cohort of 193 consecutive RCs performed between 2016 and 2019. Eighty (42%) of these patients received NAC and were divided in 2 comparison groups by presence (n = 26; 33%) or absence (n = 54; 67%) of PCN. Endpoints included completion of adequate NAC treatment (cisplatin-based chemotherapy for at least 4 courses), complications during NAC, post-RC complications and hospital stay. RESULTS: Overall, patients with PCN (45/193; 23%) featured a higher referral rate to NAC (58% vs. 36%, P = .01), worse glomerular filtration rates (P < .001) and more adverse events (P = .04), in comparison to non-PCN patients. In the NAC cohort, PCN patients had less adequate treatment rates (54% vs. 85%, P = .005), and more infections (35% vs, 7%; P = .008) and hospitalizations (58% vs. 13%; P < .001) during chemotherapy. Post-RC outcome was similar for both comparison groups. PCN was an independent risk factor for inadequate NAC (OR = 3.9, P = .04), and infections (OR = 11.3, P = .01) and hospitalizations (OR = 7.5, P = .004) during NAC. CONCLUSIONS: PCN in MIBC patients is a significant risk factor for inadequate NAC and adverse events during treatment. This finding may quire the rationale of NAC, potentially leading to consideration of NAC avoidance and upfront RC in PCN patients. Further survival studies with long follow-up are needed for elucidating this issue.

Localised non-metastatic sarcomatoid renal cell carcinoma: a 31-year externally verified study.

OBJECTIVE: To evaluate post-nephrectomy outcomes and predictors of cancer-specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non-sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non-metastatic sRCC. PATIENTS AND METHODS: A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC (n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non-sRCC (n = 360). The CSS at every stage between groups was assessed. Phase III ASSURE clinical trial data were used to externally validate the CSS findings. The Mann-Whitney U-test and chi-squared test compared outcomes and the Kaplan-Meier method evaluated CSS, overall survival (OS) and recurrence-free survival. Clinicopathological features associated with RCC death were evaluated using Cox proportional hazards regression. RESULTS: The median follow-up was 31.5 months. The median OS and CSS between the sRCC and Grade 4 non-sRCC groups was 45 vs 102 months and 49 vs 152 months, respectively (P < 0.001). At every stage, sRCC had worse CSS compared to Grade 4 non-sRCC. Notably, pT1 sRCC had worse CSS than pT3 Grade 4 non-sRCC. Negative predictors of CSS were sarcomatoid features, non-clear cell histology, positive margins, higher stage (pT3/pT4), and use of minimally invasive surgery (MIS). ASSURE external verification showed worse CSS in patients with sRCC (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.12-2.36; P = 0.01), but not worse outcomes in MIS surgery (HR 1.39, 95% CI 0.75-2.56; P = 0.30). CONCLUSIONS: Localised sRCC had worse CSS compared to Grade 4 non-sRCC at every stage. Negative survival predictors included positive margins, higher pathological stage, use of MIS, and non-clear cell histology. sRCC is an aggressive variant even at low stages requiring vigilant surveillance and possible inclusion in adjuvant therapy trials.

11-item modified frailty index and outcomes after radical cystectomy.

INTRODUCTION: To investigate the association between modified frailty index (mFI) scores and radical cystectomy outcomes. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis of 292 patients who underwent radical cystectomy between 2015 and 2019. The patients were stratified according to mFI scores (mFI 0-1 vs. mFI ≥2). Baseline characteristics were compared between groups. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS), and the secondary endpoint was the 30-day postoperative complication rate. RESULTS: One group included 164 patients with mFI 0-1 and the other included 128 patients with mFI ≥2. The cohort's median age was 69 years, and median follow-up for survivors was 33 months. Thirty-day major postoperative complication rate was 19%. Ninety patients (31%) died during the study period, 70 of them (24%) from bladder cancer. Older age, male sex, lower kidney function, and diversion to an ileal conduit were significantly more common in the mFI ≥2 group. The postoperative complication rates were comparable between groups, but the CSS and OS were significantly lower in the frailer group (p = 0.007 and p = 0.03, respectively). An mFI score ≥ 2 emerged as an independent risk factor for cancer-specific death (hazard ratio [HR] = 1.7, p = 0.03) and overall-mortality (HR = 1.8, p = 0.008). DISCUSSION: High mFI scores are associated with shorter CSS and OS after radical cystectomy. Healthcare providers should be encouraged to calculate frailty preoperatively for judicious patient selection in light of the predicted outcomes.

Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

Complete Blood Count Markers and C-Reactive Protein as Predictors of Testicular Viability in the Event of Testicular Torsion in Adults.

INTRODUCTION: The association between blood markers and testicular viability after testicular torsion (TT) is not well known. We evaluated the role of complete blood count markers and C-reactive protein (CRP) in predicting testicular viability after TT. METHODS: Fifty men, ≥18 years of age, operated for TT between the years 2015-2020 were enrolled. Blood markers including neutrophil-, lymphocyte-, and platelet count, and CRP were obtained. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were calculated. The study outcome was testicular salvage. RESULTS: Median age was 23 years (interquartile range [IQR]: 21, 31). Median duration of torsion was 10 h (IQR: 6, 42). Sonographic texture of the testis was homogenous in 27 (56%) patients and heterogenous in 21 (44%). During scrotal exploration, 36 patients (72%) underwent orchiopexy and 14 (28%) underwent orchiectomy. Patients who underwent orchiopexy were younger (22 years vs. 31 years, p = 0.009), had a shorter duration of torsion (median 8 h vs. 48 h, p < 0.001), and a homogenous texture on scrotal ultrasound (76.5 vs. 7.1%, p < 0.001). Median NLR, PLR, and CRP were higher among patients who underwent orchiectomy; however, these differences did not reach statistical significance. Patients with heterogenous echotexture were significantly more likely to undergo orchiectomy (odds ratio = 42, 95% confidence interval: 7, 831, adjusted p value = 0.009). CONCLUSIONS: We found no association between blood-based biomarkers and testicular viability after TT; however, testicular echotexture significantly predicted outcome.

The role of malnutrition universal screening tool in predicting outcomes after radical cystectomy.

PURPOSE: The Malnutrition Universal Screening Tool integrates body mass index, unintentional weight loss and present illness to assess risk for malnutrition. The predictive role of 'MUST' among patients undergoing radical cystectomy is unknown. We investigated the role of 'MUST' in predicting postoperative outcomes and prognosis among patients after RC. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis of 291 patients who underwent radical cystectomy in 6 medical centers between 2015 and 2019. Patients were stratified to risk groups according to the 'MUST' score [low risk (n = 242) vs. medium-to-high risk (n = 49)]. Baseline characteristics were compared between groups. Endpoints were 30-day postoperative complications rate, cancer-specific-survival and overall survival. Kaplan-Meier curves and Cox-regression analyses were used to evaluate survival and identify predictors of outcomes. RESULTS: Median age of the study cohort was 69 years (IQR 63-74). Median duration of follow up for survivors was 33 months (IQR 20-43). Thirty-day major postoperative complications rate was 17%. Baseline characteristics were not different between the 'MUST' groups, and there was no difference in early post-operative complication rates. CSS and OS were significantly lower (p ≤ 0.02) in the medium-to-high-risk group ('MUST' score≥1) with estimated 3-year CSS and OS rates of 60% and 50% compared to 76% and 71% in the low-risk group, respectively. On multivariable analysis, 'MUST'≥1 was an independent predictor of overall- (HR = 1.95, p = 0.006) and cancer-specific-mortality (HR = 1.74, p = 0.05). CONCLUSIONS: High 'MUST' scores are associated with decreased survival in patients after radical cystectomy. Thus, the 'MUST' score may serve as a preoperative tool for patient selection and nutritional intervention.

The role of tumor density in predicting significant cancer on targeted biopsy of the prostate.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) is central to diagnosing prostate cancer; however, not all imaged lesions represent clinically significant tumors. We aimed to evaluate the association between the relative tumor volume on mpMRI and clinically significant prostate cancer on biopsy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 340 patients who underwent combined transperineal targeted and systematic prostate biopsies between 2017 and 2021. Tumor volume was estimated based on the mpMRI diameter of suspected lesions. Relative tumor volume (tumor density) was calculated by dividing the tumor and prostate volumes. The study outcome was clinically significant cancer on biopsy. Logistic regression analyses were used to evaluate the association between tumor density and the outcome. The cutoff for tumor density was determined with ROC curves. RESULTS: Median estimated prostate and peripheral zone tumor volumes were 55cm3 and 0.61cm3, respectively. Median PSA density was 0.13 and peripheral zone tumor density was 0.01. Overall, 231 patients (68%) had any cancer and 130 (38%) had clinically significant cancer. On multivariable logistic regression age, PSA, previous biopsy, maximal PI-RADS score, prostate volume, and peripheral zone tumor density were significant predictors of outcome. Using a threshold of 0.006, the sensitivity, specificity, positive and negative predictive values of peripheral zone tumor density were 0.9, 0.51, 0.57, and 0.88, respectively. CONCLUSION: Peripheral zone tumor density is associated with clinically significant prostate cancer in patients with PI-RADS 4 and 5 mpMRI lesions. Future studies are required to validate our findings and evaluate the role of tumor density in avoiding unnecessary biopsies.

External validation of a simplified prognostic model for survival in patients with extrinsic malignant ureteral obstruction treated with tandem ureteral stents - a retrospective cohort study.

INTRODUCTION: Prognostic models of survival can identify patients with extrinsic malignant ureteral obstruction who will benefit from long-term drainage as offered by tandem ureteral stents. The study aims to validate a simplified prognostic model published by Cordeiro et al. and to identify additional prognostic predictors in a cohort of patients drained solely with tandem ureteral stents. METHODS: Medical records of consecutive patients who underwent drainage of malignant ureteral obstruction with tandem ureteral stents between 2007 and 2020 were reviewed retrospectively; patients with benign ureteral obstruction were excluded. Risk factors for survival included were: [1] the number of malignancy-related events (categorized as ≥4 and <4) and [2] the Eastern Cooperative Oncology Group Index (categorized as ≥2 and <2)]. Patients with ≥1 risk factor were grouped as intermediate-unfavorable risk and those without risk factors as favorable risk. The Kaplan-Meier and log-rank tests were used for survival analysis. Univariable and multivariable Cox regression analyses were used to identify predictors of outcome. RESULTS: The study cohort consisted of 65 patients; the median age was 60 years (IQR 51-72). The median follow-up time from diagnosis of hydronephrosis was 51 months (IQR 38-64). Estimated probabilities of survival at 1 month, 6 months 1 year, and 2 years were 100%, 87%, 75% and 57%, respectively in the favorable risk group (n = 40), and in the intermediate-unfavorable risk group (n = 25), 96%, 72%, 52%, and 20%, respectively, (p = .003). On multivariable analysis, the presence of ≥4 malignancy-related events (HR = 2.04, 95% CI [1.07-3.86], p = .03) and lung metastasis (HR = 2.37, 95% CI [1.0-5.6], p = .05) were associated with shorter survival. CONCLUSIONS: Our findings validate the prognostic model published by Cordeiro et al. The model can be applied when counseling patients being considered for drainage with tandem ureteral stents.

Association between COVID-19 Burden, Population Vaccination Status, and Urologic Oncology Surgery Volume: A National Multicenter Cross-Sectional Study.

Initial deleterious effects of the COVID-19 pandemic on urologic oncology surgeries are well described, but the possible influence of vaccination efforts and those of pandemic conditions on surgical volumes is unclear. Our aim was to examine the association between changing vaccination status and COVID-19 burden throughout the pandemic and the volume of urologic oncology surgeries in Israel. This multi-center cross-sectional study included data collected from five tertiary centers between January 2019 and December 2021. All 7327 urologic oncology surgeries were included. Epidemiological data were obtained from the Israeli Ministry of Health database. A rising trend in total urologic oncology surgery volumes was observed with ensuing COVID-19 wave peaks over time (X2 = 13.184, df = 3, p = 0.004). Total monthly surgical volumes correlated with total monthly hospitalizations due to COVID-19 (R = -0.36, p = 0.015), as well as with the monthly average Oxford Stringency Index (R = -0.31, p = 0.035). The cumulative percent of vaccinations and of new COVID-19 cases per month did not correlate with total monthly urologic surgery volumes. Our study demonstrates the gradual acclimation of the Israeli healthcare system to the COVID-19 pandemic. However, hospitalizations due to COVID-19, as well as restriction stringency, correlate with lower volumes of urologic oncological surgeries, regardless of the population's vaccination status.

Urethral Melanoma - Clinical, Pathological and Molecular Characteristics.

BACKGROUND: Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease. OBJECTIVE: To describe the clinical, pathological, and molecular characteristics of urethral melanoma. METHODS: We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT (n = 5) and gene-specific PCR data on BRAF, KIT, and/or NRAS (n = 8) were compared to genomic data of cutaneous melanomas (n = 143), vulvar/vaginal melanomas (n = 24), and primary non-melanoma urethral tumors (n = 5) from our institutional database. RESULTS: Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment.Primary urethral melanomas showed a higher frequency of TP53 mutations compared to cutaneous (80.0% vs. 18.2%, p = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, p = 0.04). BRAF mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, p = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas (p = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, p = 0.03). CONCLUSIONS: Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.

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.

Impact of COVID-19 pandemic on patients with obstructing urinary stones complicated by infection.

Objective: To assess the influence of COVID-19-imposed life changes on presentation and outcomes of patients with obstructing urinary stones complicated by infection. Patients and methods: All patients presenting with obstructing urinary stones and infection 1 year before the pandemic (March 2019 to February 2020; n = 66) and 1 year since its onset (March 2020 to February 2021; n = 45) were enrolled. Demographics, clinical presentation, laboratory panel, stone characteristics and outcomes were compared between groups. Univariate and multivariate logistic regression models were performed for analysis. Results: The COVID-19 period was characterised by younger patients, female predominance, higher temperature at presentation and more bilateral obstructing stones (p < 0.05). The admission rate to intensive care units was double that of the pre-pandemic period, whereas time between diagnosis and treatment was similar. The univariate analysis revealed higher rates of severe sepsis (odds ratio [OR] = 3, p = 0.01), systemic inflammatory response syndrome (SIRS) ≥ 2 (OR = 2.9, p = 0.01) and risk, injury, failure, loss of kidney function and end-stage kidney (RIFLE) criteria ≥ 1 (OR = 2.2, p = 0.04) in the pandemic period group. The multivariate analyses revealed the COVID-19 period as being the sole variable associated with severe sepsis (OR = 3.1, p = 0.02), SIRS ≥ 2 (OR = 3.8, p = 0.005) and RIFLE ≥ 1 (OR = 2.6, p = 0.05). Conclusions: The pandemic period was characterised by a worse clinical state at presentation of patients with obstructing urinary stones complicated by infection, probably reflecting delay in arrival to emergency services.

Systemic Immunological Determinants of Oncological Outcomes After Surgery for Localized Renal Cell Carcinoma.

INTRODUCTION & OBJECTIVES: In systemic therapy trials, a decreasing neutrophil-to-lymphocyte ratio (NLR) after treatment for metastatic renal cell carcinoma (RCC) has been associated with improved oncologic outcomes. Paradoxically, for patients with localized RCC treated with upfront surgery the opposite effect has been reported. We thus aimed to evaluate NLR dynamics on localized RCC recurrence. MATERIALS AND METHODS: Treatment naïve patients with localized RCC managed surgically between 2005 and 2020 were included. Preoperative NLR was calculated within 6-weeks prior to surgery and postoperative NLR was calculated between 4 and twelve-weeks after surgery. Patients were followed for disease recurrence, noting metastatic sites and postoperative infections. Cox regression were used to determine whether the relative change in postoperative NLR was associated with metastasis-free survival (MFS) and cancer-specific survival (CSS), adjusted for preoperative NLR. RESULTS: In the cohort of 3310 patients, 996 (30%) had postoperative NLR available. These patients generally had more advanced disease, with 100 developing metastases and 38 dying from kidney cancer. Median MFS follow-up was 4.4 years. Decreasing 2-month postoperative NLR was associated with non-statistically significant worse MFS and CSS (HR 0.79, 95% 0.50, 1.24, P = .3; HR 0.83, 95% C.I. 0.40, 1.73; P = .6). On sensitivity analysis, across all NLR measurements, with NLR as a time-dependent covariate, results were similar, with a declining NLR associated with adverse MFS (HR 0.85, 95% CI 0.69, 1.30, P-value = .10), though not meeting conventional levels of significance. CONCLUSION: In higher-risk localized RCC patients, postoperative NLR is not suitable as a biomarker for predicting recurrences.

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.

68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography for patients with favorable intermediate-risk prostate cancer.

INTRODUCTION: Current guidelines do not support the use of pretreatment imaging in patients with favorable intermediate-risk prostate cancer. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether pretreatment 68Ga-PSMA PET/CT is beneficial for identifying pathological lymph node involvement (LNI) and adverse pathology among patients with favorable intermediate-risk prostate cancer. METHODS: We reviewed 88 patients with favorable intermediate-risk prostate cancer who underwent 68Ga-PSMA PET/CT prior to radical prostatectomy and lymph node dissection from 2016-2020. The primary endpoint was the presence of pathological LNI. Association between pretreatment characteristics and outcomes were evaluated. RESULTS: Preoperative 68Ga-PSMA PET/CT showed suspicious uptake in lymph nodes in 4/88 patients (5%), hence, 20 patients would need to be scanned to identify a patient with a positive lymph node on imaging. Two patients had pathological LNI, only one of whom showed 68Ga-PSMA PET/CT uptake prior to surgery. The sensitivity, specificity, positive predictive value, and negative predictive values of 68Ga-PSMA PET/CT for identifying LNI were 50%, 97%, 25%, and 99%, respectively. After surgery, four patients had evidence of prostate-specific antigen (PSA) persistence. The rate of PSA persistence was higher among patients with LNI on preoperative 68Ga-PSMA PET/CT (2/4, 50% vs. 2/84, 2%, p=0.009). CONCLUSIONS: Preoperative imaging of favorable intermediate-risk prostate cancer patients using 68Ga-PSMA PET/CT showed a low yield for identifying patients at higher risk. Consistent with current guidelines, our findings do not support the routine use of PET/CT in this group of patients. Future prospective studies are needed to validate our findings.

Parental Regret Following Decision to Revise Circumcision.

Purpose: Revision surgery for the removal of excess foreskin after circumcision is a common procedure. The decision regret scale (DRS) is a validated questionnaire which assesses regret after medical decision making. The aim was to evaluate parental regret by means of the DRS and querying about factors associated with regret about deciding to revise their child's circumcision. Patients and Methods: Included were all pediatric patients who underwent revision of neonatal circumcision in a single center between 2010 and 2016. Excluded were children who underwent revision for reasons other than excess foreskin, those who underwent additional surgical procedures during the same anesthetic session, and those who had undergone previous penile surgery other than circumcision. Response to the DRS questionnaire was by a telephone call with the patient's parent. Regret was classified as none (a score of 0), mild (1-25), or moderate-to-strong (26-100). Surgical and baseline demographic data were obtained from the departmental database and compared between the no regret and regret groups. Results: Of the 115 revisions of circumcisions performed during the study period, 52 fulfilled the inclusion criteria, and the parents of 40 (77%) completed the DRS questionnaire. Regret was reported by 11/40 [28%: nine as mild (23%) and two as moderate-to-strong (5%)]. The average age of the child in the regret group was 17 months compared to 18 months in the no regret group (p = 0.27). The median weight percentile was 43% in both groups. Surgical variables, including anesthesia type (caudal vs. no block, p = 0.65), suture type (polyglactin vs. poliglecaprone, p = 0.29), operation time (28 vs. 25 min, p = 0.59), and anesthesia time (55 vs. 54 min, p = 0.57) were not significantly different between the groups. Conclusions: Regret for deciding upon revision surgery for removal of excess foreskin post-circumcision was reported by 27.5% of parents of children who underwent revision. No clinical, surgical, or demographic characteristics predicted parental decisional regret.