Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

Long-term survival of patients aged 80 years or older treated with radical prostatectomy for prostate cancer.

BACKGROUND: Radical prostatectomy (RP) is the gold standard for clinically localized prostate cancer (PCa) patients with life expectancy (LE) of at least 10 years. We examined long-term survival of men aged 80 years or older treated with RP and we attempted to identify criteria based on age and comorbidities that could predict survival of at least 10 years after RP, to identify those that might be considered for RP. PATIENTS AND METHODS: In Surveillance Epidemiology and End Results (SEER)-Medicare-linked database, we identified 234 octo- and nonagenarians with clinical T1, T2 or T3 PCa treated with RP between 1991 and 2009. Kaplan-Meier analyses examined 10-year survival patterns. Multivariable Cox regression analyses focused on the combined effect of age and/or Charlson Comorbidity Index (CCI) after adjusting for different confounders. RESULTS: The 10-year overall survival (OS) and cancer specific mortality (CSM) rates in the overall population were 51 and 9.9%. In individuals aged 80-81 years old, the 10-year OS was 62.4 vs. 39.6% in older patients (p = 0.001). Moreover, combination of age 80-81 with CCI = 0 yielded 10-year OS of 67.9 vs. 28.5% in older and sicker patients (p < 0.001). Age 80-81, absence of comorbidities and the combination of age 80-81 with CCI = 0, represented independent predictors of lower overall mortality (all p ≤ 0.01). CONCLUSIONS: Two out of three individuals selected for RP aged 80-81 years and without comorbidities, fulfill the criterion of LE of 10 years or more. Therefore, elderly PCa individuals can be suitable for surgical management, if appropriately selected, based on LE criterion.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

BACKGROUND: We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). METHODS: Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. RESULTS: Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). CONCLUSIONS: We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Treatment of M1a/M1b prostate cancer with or without radical prostatectomy at diagnosis.

BACKGROUND: The aim of the study was to evaluate survival and perioperative outcomes of metastatic prostate cancer (mPCa) patients treated with surgery or androgen deprivation treatment (ADT) only. METHODS: We retrospectively selected 47 metastatic PCa patients treated at a single center (Mayo Clinic, Rochester, MN) by two urologists (RJK and EK) between 2007 and 2014. Overall, 31 (66%) underwent radical prostatectomy (RP) with or without adjuvant therapies and 16 (34%) underwent ADT only. Surgical patients were treated by a single surgeon (RJK). Complications and functional outcomes were recorded for surgery group. Cancer-specific mortality (CSM) was analyzed by Kaplan-Meier estimation. Univariable Cox regression analyses were used to test the risk factors associated with CSM in mPCa patients treated with RP. RESULTS: Median age at diagnosis was 61 years. During median follow-up 38.8 months, 12 deaths were recorded. At 5 years, the overall CSM-free survival rate of the whole cohort was 57.9%. When patients were stratified according to the treatment, CSM-free survival rate at 5 years was 62% and 46% for patients who underwent surgery and ADT, respectively (P=0.3). Median length of stay was 3 days, with a 30 days readmission rate of 9.7%. The 30-day all complication rate was 29% (n=9). Specifically, we recorded: 2 lymphoceles (6.5%), 2 wound infection (6.5%), 2 ileus (6.5%), 2 hematoma (6.5%) and 1 anastomosis leak (3.2%). Within 90 days after surgery, 2 (6.5%) and 5 (16.1%) patients needed 1-2 supportive and 3 or more pads, respectively. However, continence was achieved by all treated patients during the follow-up period. CONCLUSIONS: We demonstrated the feasibility of local surgical treatment of primary tumor in mPCa patients. However, in the short term, no survival benefits have been observed for patients treated with surgery when compared with patients treated with ADT only. Further prospective studies are warranted to explore the treatment of M1a/M1b prostate cancer patients.

Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

The surgical management of patients with clinical stage T4 bladder cancer: A single institution experience.

INTRODUCTION: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution. METHODS: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery. RESULTS: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04). CONCLUSIONS: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease.

The impact of local treatment of the primary tumor site in node positive and metastatic prostate cancer patients.

BACKGROUND: Surgical treatment of the primary tumor in patients with metastatic prostate cancer (mPCa) is gaining traction. We discuss the biological rational and the existing literature on this approach. METHODS: We reviewed the literature regarding surgical management of advanced and mPCa disease. RESULTS: Surgical removal of the primary tumor despite metastases is becoming a standard in an increasing number of malignancies. Basic science data support the use of surgical removal of the prostate in metastatic PCa. In addition, durable long-term survival has been reported in patients with node-positive PCa treated with radical prostatectomy (RP) as mono or multimodal approach. Based on these data, several groups have demonstrated the feasibility and safety of RP in the metastatic setting. Retrospective series have also reported an improvement in survival for metastatic patients treated with RP in addition to systemic treatment. CONCLUSIONS: Although no level I data exist at this time to support the use of RP in clinically node-positive or mPCa patients, retrospective data together with basic research data and experience from other malignancies suggest that treatment of the primary tumor, in form of a RP, is safe and could improve long-term quality of life and survival. However, prospective evaluations are requested to validate these findings before including in the standard clinical practice.

Relationships among ensiling, nutritional, fermentative, microbiological traits and contamination in corn silages addressed with partial least squares regression.

The objective of this work was to reduce the predictor dimensionality and to develop a model able to forecast contamination in corn silages. A survey on 33 dairy farms was performed, and samples from core, lateral, and apical parts of the feed-out face of corn silage bunkers were analyzed for chemical, biological (digestible and indigestible NDF), fermentative (pH, ammonia nitrogen, lactic acid, VFA, and ethanol), and microbiological (yeasts and molds) traits. Corn silage samples were analyzed for cell and spore counts by adoption of a molecular DNA-based method. A partial least squares (PLS) regression with a leave-one-out cross-validation method was used to reduce the dimensionality of the original predictors ( = 30) by projecting the independent variables into latent constructs. In a first step of the model development, the importance of independent variables in predicting contamination was assessed by plotting factor loadings of both dependent and independent variables on the first 2 components and by verifying for each predictor the variable influence on projection values adopting the Wold's criterion as well as the entity of standardized regression coefficients. Three ensiling characteristics (bunker type, presence of lateral wrap plastic film, and penetration resistance as a measurement of the ensiled mass density), a chemical trait (DM), 9 characterizations of the fermentative profile (pH, ammonia nitrogen, acetic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, ethanol, and lactic acid), and 2 microbiological traits (yeasts and molds) were retained as important terms in the PLS model. Three reduced-variable PLS (rPLS) regressions-the first based on ensiling, chemical, fermentative, and microbiological retained important variables (rPLSecfm); the second based on chemical, fermentative, and microbiological retained important traits (rPLScfm); and the last based on only chemical and fermentative retained important variables (rPLScf)-were performed. The model that best fit the measurements was rPLSecfm. The rPLScfm and rPLScf models had similar regression performances but higher mean square errors of prediction than rPLSecfm. However, all tested models seemed adequate to rank corn silages for low, medium, and high risks of contamination. To avoid the visit on farm by trained people required to measure penetration resistance, the use of the rPLScf model is suggested as a useful tool to assess the risk of in corn silage.

Patterns and prognostic significance of clinical recurrences after radical cystectomy for bladder cancer: A 20-year single center experience.

OBJECTIVE: Patients treated with radical cystectomy (RC) due to bladder cancer (BCa) face high risk of clinical recurrence. The aim of our study was to describe recurrence patterns and characteristics related to survival in patients treated with RC due to BCa. METHODS: Years 1992-2012 of a prospectively maintained institutional RC registry were queried for clinical localized urothelial BCa patients. Clinical recurrences were categorized as local, distant or secondary urothelial recurrences. Kaplan Meier analysis assessed time to cancer specific mortality (CSM). Multivariable Cox regression models were constructed to predict recurrence and CSM after recurrence. RESULTS: Data from 1110 patients with urothelial non-metastatic BCa at RC were analyzed with 7.5 years of median follow up. Overall, 324 patients experienced recurrence and 200 (61.7%) were single site recurrence. The locations were: 43 local (22 cystectomy bed and 21 pelvic lymph node dissection template), 138 distant (36 lung, 19 liver, 52 bone, 17 extra pelvic LN, 7 peritoneal, 4 brain and 3 others) and 19 secondary urothelial carcinoma (11 upper urinary tract, 8 urethra). Significant independent predictors of overall recurrence were pathological stage pT3/T4 vs. pT0-2, pathological N positive status and positive surgical margin. Median overall survival after recurrence was 18 months. At multivariate analysis, pathological T3 (Hazard ratio [HR]: 1.62), T4 (HR: 1.58), interval from RC to recurrence (HR: 0.92) and distant (HR: 2.57) recurrences were independently associated with CSM (all p < 0.05). CONCLUSIONS: Overall, one out of three patients treated with RC face recurrence during follow up. Early and distant recurrences are associated with shortest survival expectancies.

Short communication: The effect of an exogenous enzyme with amylolytic activity on gas production and in vitro rumen starch degradability of small and large particles of corn or barley meals.

The objective of this study was to evaluate the effect of exogenous amylase supplementation on gas production and on in vitro rumen starch degradability (IVSD) of different sized particles of corn and barley meals (Cm and Bm, respectively). An aqueous liquid amylase formulation from Bacillus licheniformis was tested at 3 enzyme doses (EnzD; 0, 300 and 1,500 kilo novo units/kg of dry matter) on small (<750 µm) and large (≥750 µm) particle size (PS) of Cm and Bm. Data were analyzed according to a randomized complete block design with a factorial arrangement of treatments; the main tested effects were PS, EnzD, and their interaction. Fermentation run entered in the model as random effect. The mixed rumen fluid was collected from 2 rumen-fistulated Holstein dry dairy cows fed at maintenance (forage:concentrate ratio of 80:20; 12% crude protein; 55% amylase-treated neutral detergent fiber). Small particles of both Cm and Bm had a greater rate of fermentation and shorter lag time than large particles. The rate of starch degradation was greater for small than for large particles of Bm, being 0.187 and 0.125 1/h, respectively. Conversely, the rate of starch degradation of Cm averaged 0.063 1/h and was similar among treatments. Enzyme supplementation tended to reduce lag time and to increase rate of fermentation for both PS of Cm and Bm, with a more pronounced effect for small PS. A limited EnzD effect was measured for IVSD data and rate of starch degradation; PS influenced fermentation parameters and the magnitude of starch degradation more than EnzD. Supplementation with exogenous amylase influenced the rumen fermentation pattern of small and large PS of Cm and Bm, even if the effect of the enzyme supplementation differed according to the PS of cereal meals.

Non-surgically related causes of erectile dysfunction after bilateral nerve-sparing radical prostatectomy.

BACKGROUND: Erectile dysfunction (ED) represents one of the most common long-term side effects in prostate cancer (PCa) patients treated with bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to assess the influence of non-surgically related causes of ED in patients treated with BNSRP. METHODS: Overall, 716 patients treated with BNSRP were retrospectively identified. All patients had complete data on erectile function (EF) assessed by the Index of Erectile Function-EF domain (IIEF-EF) and depressive status assessed by the Center for Epidemiologic Studies-Depression (CES-D) questionnaire. EF recovery was defined as an IIEF-EF of ⩾22. Kaplan-Meier analyses assessed the impact of preoperative IIEF-EF, depression and adjuvant radiotherapy (aRT) on the time to EF recovery. Multivariable Cox regression models were used to test the impact of aRT on EF recovery after accounting for depression and baseline IIEF-EF. RESULTS: Median follow-up was 48 months. Patients with a preoperative IIEF-EF of ⩾22 had substantially higher EF recovery rates compared with those with a lower IIEF-EF (P<0.001). Patients with a CES-D of <16 had significantly higher EF recovery rates compared to those with depression (60.8 vs 49.2%; P=0.03). Patients receiving postoperative aRT had lower rates of EF compared with their counterparts left untreated after surgery (40.7 vs 59.8%; P<0.001). These results were confirmed in multivariable analyses, where preoperative IIEF-EF (P<0.001), depression (P=0.04) and aRT (P=0.03) were confirmed as significant predictors of EF recovery. CONCLUSIONS: Preoperative functional status and depression should be considered when counseling PCa patients regarding the long-term side effects of BNSRP. Moreover, the administration of aRT has a detrimental effect on the probability of recovering EF after BNSRP. This should be taken into account when balancing the potential benefits and side effects of multimodal therapies in PCa patients.

Effect of the inclusion of dry pasta by-products at different levels in the diet of typical Italian finishing heavy pigs: Performance, carcass characteristics, and ham quality.

The effect of pasta inclusion in finishing pig diets was evaluated on growth performance, carcass characteristics, and ham quality. Pigs (144) were assigned to 4 diets with different pasta levels: 0 (control, corn-based diet), 30, 60, or 80%. Pigs fed pasta had greater (linear, P<0.01) feed intakes than controls. Pasta increased (quadratic, P<0.01) carcass weight and dressing percentage reaching the highest values at 30% inclusion level, and reduced (linear, P<0.01) the Longissimus thoracis et lumborum thickness. Pasta decreased (linear, P<0.01) linoleic acid and polyunsaturated fatty acid levels in subcutaneous (fresh and seasoned hams) and intramuscular (seasoned hams) fat, and enhanced saturated fatty acid content in subcutaneous fat (fresh hams: quadratic, P<0.01; seasoned hams: linear, P=0.03). Proteolysis index, colour, weight losses, and sensory properties (excepted extraneous taste) of the hams were unaffected by the pasta. Pasta could be considered as an ingredient in the diet for typical Italian finishing heavy pigs.

Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection.

BACKGROUND: The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa. METHODS: We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models. RESULTS: The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03). CONCLUSIONS: In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.