Associations of dietary patterns with kidney cancer risk, kidney cancer-specific mortality and all-cause mortality among postmenopausal women.

BACKGROUND: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) are novel measures of dietary quality associated with insulin hypersecretion or chronic inflammation, respectively, whereas the Healthy Eating Index (HEI-2015) measures adherence to the Dietary Guidelines for Americans (DGA). We evaluated associations of EDIH, EDIP and HEI-2015 on the risk of both kidney cancer development and mortality. METHODS: We calculated the dietary scores from baseline food frequency questionnaires among 115,830 participants aged 50-79 years in the Women's Health Initiative. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for kidney cancer risk, kidney cancer-specific mortality and all-cause mortality, per 1-standard deviation increment in dietary pattern scores. RESULTS: Higher EDIH was associated with greater risk of kidney cancer development [HR, 1.12; 95%CI, (1.01,1.23)], kidney cancer-specific death [1.22(0.99,1.48)], and all-cause mortality, [1.05(1.02,1.08)]. Higher HEI-2015 was associated with lower risk of kidney cancer development, [0.85(0.77, 0.94)], kidney cancer-specific death, [0.84(0.69,1.03)] and all-cause mortality, [0.97(0.95,1.00)]. However, EDIP was not significantly associated with outcomes. Associations did not differ by BMI categories. CONCLUSIONS: Low-insulinemic dietary patterns and higher quality diets, are worthy of testing in dietary pattern intervention trials for kidney cancer prevention and improved survivorship.

Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance.

PURPOSE: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer. MATERIALS AND METHODS: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density. Nonparametric testing was performed to compare the median Genomic Prostate Score™ and the likelihood of favorable pathology findings between quartiles of disease volume. RESULTS: We identified 112 (37.8%) and 184 men (62.2%) at NCCN very low and low risk, respectively. Median scores did not differ significantly between disease volume quartiles (all p >0.05). However, the median likelihood of favorable pathology findings statistically differed between volume quartiles (all <0.05). Seven of the 105 men (6.3%) with very low risk disease were reclassified at low risk and 13 of 181 (7.2%) with low risk disease were reclassified at intermediate risk. Genomic disease reclassification did not depend on biopsy tumor volume. CONCLUSIONS: In patients with NCCN very low and low risk prostate cancer genomic scores did not demonstrate meaningfully significant differences by volume based on clinically established cutoff points. Moreover, genomic scores identified and reclassified men with higher risk disease despite generally acceptable surveillance characteristics in this group according to grade and volume. This suggests that in patients at low risk the tumor biological potential measured by genomics rather than by volume should inform decisions on active surveillance candidacy.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features.

PURPOSE: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. MATERIALS AND METHODS: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. RESULTS: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p <0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). CONCLUSIONS: Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.

PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.

Surgical Salvage of Thermal Ablation Failures for Renal Cell Carcinoma.

PURPOSE: Cryoablation and radio frequency ablation are attractive modalities for small renal masses in patients with substantial comorbidities. However, salvage extirpative therapy for local recurrence after thermal ablation can be challenging due to associated perinephric fibrosis. MATERIALS AND METHODS: Patients with thermal ablation refractory tumors requiring surgical salvage from 1997 to 2013 were identified and retrospectively reviewed. RESULTS: A total of 27 patients were treated surgically after cryoablation (18) or radio frequency ablation (9) failed. Subjective assessment indicated moderate/severe fibrosis in 22 cases (81%). Partial nephrectomy was preferred in all patients but was not possible in 12, primarily due to unfavorable tumor size/location. In the intended partial nephrectomy group (15) open surgery was performed in all patients and completed in 14, with the procedure aborted in 1 due to extensive perinephric fibrosis. Radical nephrectomy was planned in 12 patients, of whom 8 were treated laparoscopically with 1 requiring conversion to open. Median estimated blood loss was 225 ml. Overall 17 patients experienced no complications and 4 had minor complications. However, 6 patients experienced more significant complications (Clavien III-IVb). Since January 2008 partial nephrectomy was performed more frequently (12 of 17, or 71% vs 2 of 10, or 20% for previous cases, p=0.02). CONCLUSIONS: Surgical salvage after failed thermal ablation is feasible in most instances, and partial nephrectomy is often possible but can be challenging due to associated perinephric fibrosis. The difficulty of surgical salvage should be recognized as a potential limitation of the thermal ablation treatment strategy. Prospective studies of thermal ablation vs partial nephrectomy should be prioritized to provide higher quality data about the merits and limitations of each approach.

A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy.

Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) µmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) µmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) µmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) µmol/l ( - 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.

Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research.

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).

Quality of lymphadenectomy is equivalent with robotic and open cystectomy using an extended template.

PURPOSE: Extended lymph node dissection for bladder cancer provides better staging, cancerous node removal and potentially survival. Minimally invasive techniques have been criticized about the ability to adequately perform extended lymph node dissection. We compared the extended lymph node dissection quality of robotic and open cystectomy by assessing node yield and positivity. MATERIALS AND METHODS: We compared extended lymph node dissection in 120 open and 35 robotic cystectomy cases. Extended lymph node dissection included skeletonization of structures in each nodal group below the aortic bifurcation (common iliac, external iliac, obturator, hypogastric and presacral nodes). Nodes were processed identically but submitted as 1 or 2 packets for robotic cases and as 10 or more packets for open surgery cases. RESULTS: The mean±SD node count in the open group was 36.9±14.8 (range 11 to 87) and in the robotic group the mean yield was 37.5±13.2 (range 18 to 64). Only 12 of 120 open (10%) and 2 of 35 robotic (6%) cases had fewer than 20 nodes. A total of 36 open (30%) and 12 robotic (34%) cases were node positive. Open extended lymph node dissection identified 80% and 90% confidence of accurate staging as pN0 when obtaining 23 and 27 nodes, respectively. A node count of 23 or 27 was achieved in 87% and 77% of open cases, and in 91% and 83% of robotic cases, respectively. Of patients with open surgery 36% received neoadjuvant chemotherapy compared to 31% of those with robotic surgery. CONCLUSIONS: No difference was identified in the lymph node yield or the positive node rate when comparing open and robotic extended lymph node dissection. Local recurrence and survival data are needed to confirm whether the 2 techniques are oncologically equivalent.

The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery.

PURPOSE: We investigated the effect of sunitinib on locally advanced primary renal carcinoma tumors and the ability to facilitate subsequent surgery. MATERIALS AND METHODS: Patients with an unresectable primary renal tumor, with or without distant metastases, received 50 mg sunitinib with continuous daily dosing in a phase II trial. Computerized tomography was performed every 12 weeks to determine surgical resectability. The primary end point of the trial was the percentage of patients with renal cell carcinoma and initially unresectable primary tumors who could undergo nephrectomy after sunitinib therapy. RESULTS: Of 30 patients enrolled in the study (19 with distant metastases) 28 (35 total renal tumors) were evaluable for response. The median change in primary renal cell carcinoma tumors was a 22% decrease, corresponding to a median absolute reduction of 1.2 cm. The median reduction in primary renal cell carcinoma tumors of clear cell histology was -28% (absolute reduction 1.7 cm) compared to a 1.4% increase (0.1 cm absolute increase) in nonclear cell tumors. Of these patients 13 (45%) met the primary end point of being able to undergo nephrectomy after preoperative sunitinib. All patients had viable renal cell carcinoma in the surgical specimen and surgical morbidity was consistent with prior experience of nephrectomy in patients without preoperative therapy. CONCLUSIONS: Sunitinib as initial therapy in patients with locally advanced features of the primary tumor was feasible and resulted in an antitumor effect that enabled subsequent surgery in a subset of patients. Further prospective study is required to refine the most suitable application of this approach.

Upper and middle trunk brachial plexopathy after robotic prostatectomy.

We describe 3 patients who developed injury of upper and middle brachial plexus trunks during robotic-assisted prostatectomy, and review factors potentially associated with this type of injury. Three patients underwent robotic-assisted prostatectomy. Surgical exposure was facilitated by steep head-down tilt position. To secure patients and prevent sliding on the operating table, shoulders were supported with moldable beanbags. In all 3 cases, the left arm was abducted to approximately 90°, and the right arm was adducted. Postoperatively, all patients were diagnosed with left arm upper and middle trunk brachial plexopathies. The combination of arm abduction, extreme head-down position, and shoulder immobilization with beanbags resulted in several mechanistic forces that may have contributed to the development of brachial plexopathy in our patients. Steep head-down tilt may result in cephalad slide of the torso in relation to an abducted arm. When shoulder restraints are used to secure the patient, the compensatory movement of the shoulder girdle of an abducted arm is impeded. This may result in injurious stretching and compression of the brachial plexus, especially the upper and middle trunks. When steep head-down position is needed to facilitate surgical exposure, clinicians should consider adduction and tucking of both arms, and use of other methods to prevent sliding on the operating room table that do not require the use of restraints across the shoulder girdle.

Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure.

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF.

Presacral and retroperitoneal lymph node involvement in urothelial bladder cancer: results of a prospective mapping study.

PURPOSE: We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. MATERIALS AND METHODS: As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. RESULTS: A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). CONCLUSIONS: A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.

Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15.

The genetic transfer of antigen receptors provides a means to rapidly generate autologous tumor-reactive T lymphocytes. However, recognition of tumor antigens by cytotoxic T cells is only one step towards effective cancer immunotherapy. Other crucial biological prerequisites must be fulfilled to expand tumor-reactive T cells that retain a functional phenotype, including in vivo cytolytic activity and the ability to travel to tumor sites without prematurely succumbing to apoptosis. We show that these requirements are met by expanding peripheral blood T cells genetically targeted to the CD19 antigen in the presence of CD80 and interleukin-15 (IL-15). T cells expanded in the presence of IL-15 uniquely persist in tumor-bearing severe combined immunodeficiency (SCID)-Beige mice and eradicate disseminated intramedullary tumors. Their anti-tumor activity is further enhanced by in vivo co-stimulation. In addition, transduced T cells from patients with chronic lymphocytic leukemia (CLL) effectively lyse autologous tumor cells. These findings strongly support the clinical feasibility of this therapeutic strategy.

Insights on autophagosome-lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5.

Pivotal to the maintenance of cellular homeostasis, macroautophagy (hereafter autophagy) is an evolutionarily conserved degradation system that involves sequestration of cytoplasmic material into the double-membrane autophagosome and targeting of this transport vesicle to the lysosome/late endosome for degradation. EPG5 is a large-sized metazoan protein proposed to serve as a tethering factor to enforce autophagosome-lysosome/late endosome fusion specificity, and its deficiency causes a severe multisystem disorder known as Vici syndrome. Here, we show that human EPG5 (hEPG5) adopts an extended "shepherd's staff" architecture. We find that hEPG5 binds preferentially to members of the GABARAP subfamily of human ATG8 proteins critical to autophagosome-lysosome fusion. The hEPG5-GABARAPs interaction, which is mediated by tandem LIR motifs that exhibit differential affinities, is required for hEPG5 recruitment to mitochondria during PINK1/Parkin-dependent mitophagy. Lastly, we find that the Vici syndrome mutation Gln336Arg does not affect the hEPG5's overall stability nor its ability to engage in interaction with the GABARAPs. Collectively, results from our studies reveal new insights into how hEPG5 recognizes mature autophagosome and establish a platform for examining the molecular effects of Vici syndrome disease mutations on hEPG5.

How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage?

PURPOSE: Determining pathological nodal stage in patients with bladder cancer is important for prognosis. We determined how the extent of lymphadenectomy and the lymph node count influence accurate nodal staging. MATERIALS AND METHODS: The study included 120 patients who underwent at least extended lymphadenectomy at radical cystectomy. Different anatomical templates for lymphadenectomy were evaluated for nodal staging accuracy. The cumulative percent was plotted to determine a lymph node count that confidently identified node positive cases. RESULTS: The mean +/- SD total lymph node count in the study population was 36.9 +/- 14.8 at extended lymphadenectomy. Of the patients 36 (30%) had lymph node metastasis, including 14 (39%) with metastasis involving the common iliac and/or presacral lymph nodes. Limited, standard and extended lymphadenectomy accurately identified 75%, 88.9% and 100% of node positive cases, respectively. Removing 23 and 27 lymph nodes provided 80% and 90% confidence, respectively, that a case was accurately staged as pN0. No patient had lymph node metastasis above the aortic bifurcation without nodal metastasis below the aortic bifurcation and none had a change in pN stage by extending lymphadenectomy above the aortic bifurcation. CONCLUSIONS: To accurately identify node positive and negative cases, and correctly assign pN stage in node positive cases it is necessary to perform extended lymphadenectomy. Identifying at least 23 to 27 lymph nodes on final pathological evaluation provides a high level of confidence that a case is correctly staged as node positive or negative.

The Association of Urologic Oncology Fellowship Training and Diagnostic Yield of Prostate Biopsy.

OBJECTIVE: To determine the relationship between urologic oncology fellowship training (UOFT) and diagnostic yield of prostate biopsy. METHODS: Retrospective review was conducted of patients who underwent prostate biopsy across the Cleveland Clinic between 2000 and 2018. Biopsies done by urologists with and without UOFT were detailed via descriptive statistics and appropriate (chi-square, Student t, Wilcoxon rank-sum) tests. Multivariate logistic regression was used to examine the association between UOFT and positive prostate biopsy, adjusting for relevant covariates. RESULTS: A total of 11,241 biopsies by 129 urologists had complete information available for review. Sixteen urologists (12.4%) had UOFT; 113 either completed a different fellowship or no fellowship. Those with UOFT were more likely to use MRI-guided biopsy (7.80% vs 3.05%, P <.0001), more likely to get a positive biopsy (41.25% vs 32.72%, P <.0001), and more likely to obtain an adequate number (by ≥12) of cores (90.25% vs 74.53%, P <.0001). UOFT remained a significant predictor of positivity when adjusting for patient age and race, PSA, 5-alpha-reductase-inhibitor use, year of biopsy, years in practice, and type of biopsy (MRI or transrectal ultrasound guided). UOFT also predicted higher-risk biopsy (Gleason sum ≥7), adjusting for the same variables, though this association lost significance when adjusting for adequacy of biopsy. The learning curve to achieve a higher percentage of positive biopsies was steeper for nonurologic oncology fellowship trained than for UOFT urologists. CONCLUSION: UOFT is associated with higher diagnostic yield on prostate biopsy, higher uptake of MRI-guided biopsy, and less steep learning curve. This may be due to patient selection, technique, or, as we demonstrate here, adherence to guidelines.

Ureteroarterial Fistula in a Patient with an Ileal Conduit and Chronic Nephroureteral Catheter.

Background: Ureteroarterial fistula (UAF) is a rare and potentially devastating diagnosis most often associated with a combination of pelvic oncologic or vascular surgery, radiation, and chronic ureteral stents. Herein we discuss a patient with an ileal conduit urinary diversion and left nephroureteral (NU) catheter who presented with gross hematuria and hemodynamic instability. He underwent multiple negative radiologic investigations and his clinical course highlights the need for a high index of suspicion for UAF and multidisciplinary coordination with vascular surgery and interventional radiology. Case Presentation: Our patient is a 64-year-old male with a history of bladder cancer and atrial fibrillation on rivaroxiban who underwent cystoprostatectomy with ileal conduit urinary diversion. His postoperative course was complicated by subsequent mid-distal stricture of his left ureter, which was managed with balloon dilatation and a chronic indwelling NU catheter. He underwent a routine catheter exchange ∼1 year postradical cystectomy and subsequently experienced intermittent gross hematuria. He presented 5 weeks later with profound hematuria and clots through his urostomy accompanied by flank pain, weakness, and tachycardia. Throughout his hospital course he underwent two CT angiograms and a formal provocative angiogram that were all negative. He was taken to the operating room (OR) for attempted antegrade ureteroscopy, which was aborted because of pulsatile bleeding observed upon withdrawal of his stent. In collaboration with vascular surgery, he was eventually taken for provocative angiogram and covered stent graft placement that resolved the hematuria. Conclusion: This case highlights the diagnostic and care coordination challenges in patients with UAF. A high suspicion should be maintained in patients with hematuria and indwelling stents with a history of pelvic surgery and/or radiation.

Assessing the relationship between statin use and oncologic outcomes among men electing active surveillance for localized prostate cancer.

BACKGROUND: This study aims to assess the effect of statin therapy on outcomes among men managed with active surveillance. METHODS: This is a retrospective cohort study evaluating 635 men managed with active surveillance from 2005 to 2015 at a large, academic medical center. The primary endpoints of analyses are disease reclassification (i.e., change in volume or grade of cancer on subsequent biopsies after diagnosis), progression to definitive therapy with curative intent (i.e., surgery or radiotherapy), and surveillance failure-defined as the development of either biochemical failure after definitive therapy, metastases, or prostate cancer-specific mortality-among statin and non-statin users. Secondary analyses were performed to assess the effect of statin use on outcomes among men who progressed to definitive treatment. RESULTS: Three hundred fifty-six (56.1%) patients in the cohort were on statin therapy at the initiation of surveillance. The median age was 66.7 and 63.3 years among statin and non-statin users, respectively. On univariate analysis, there were no differences in the rates of disease reclassification, progression to definitive treatment, and surveillance failure between the statin and non-statin users in the cohort (all p > 0.05). There was no difference in the rate of biochemical failure among men who progressed to definitive therapy when stratified by statin use (p = 0.89). Pathologic data were available for 105 men who progressed to radical prostatectomy while on surveillance at our institution. Duration of statin use (months) was inversely correlated with adverse pathology for radical prostatectomy on both univariate (OR: 0.99; 95% CI 0.98, 0.99; p = 0.03) and multivariate analysis (OR: 0.98; 95% CI 0.97, 0.99; p = 0.02). CONCLUSION: Statin use was not associated with any clinical benefit with regard to disease reclassification, progression to definitive treatment, or surveillance failure among men selecting active surveillance at our institution. There was a 2% decrease in the odds of adverse pathology for each month of statin use among the men who progressed to radical prostatectomy while on active surveillance, but it is unclear at this time if this association has any durable impact on surveillance outcomes among men with favorable risk prostate cancer.

Older Age at Diagnosis and Initial Disease Volume Predict Grade Reclassification Risk on Confirmatory Biopsy in Patients Considered for Active Surveillance.

OBJECTIVE: To identify which active surveillance candidates benefit most from confirmatory biopsies to exclude grade underclassification. MATERIALS AND METHODS: This observational study includes 556 men diagnosed between 2002 and 2015 with Gleason 3 + 3 (GG1) disease on initial diagnostic biopsy, of whom 406 received a confirmatory biopsy within 12 months for active surveillance. Multivariable logistic regression analysis was performed to determine clinicopathologic features associated with Gleason 7 or higher (GG2+) on a confirmatory biopsy. Regression tree analysis was employed to stratify patients into select risk groups. RESULTS: Eighty-five of 406 patients (20.9%) with initially GG1 disease were reclassified to GG2+ on a confirmatory biopsy. On multivariable analysis, increasing age (per year odds ratio 1.07; 95% confidence interval 1.02-1.12; P <.01) and more positive cores at diagnosis (per core, odds ratio 1.37, 95% confidence interval 1.09-1.72; P <.01) were significantly associated with reclassification, independent of prostate volume, clinical stage, initial PSA, or confirmatory biopsy type (including magnetic resonance imaging-targeted approaches or transrectal saturation random sampling). Recursive partitioning demonstrated that age over 73 and 5 or more positive cores were factors associated with the greatest reclassification risk. CONCLUSION: In our cohort, both advancing age and additional positive cores were associated with increased odds of reclassification to GG2+ on confirmatory biopsy. In men over age 73 or with 5 or more positive cores, a repeat biopsy within 12 months may be particularly beneficial to minimize tumor grade underclassification.

Panniculectomy concurrent with anterior pelvic exenteration for recurrent cervical cancer.

BACKGROUND: Panniculectomy concurrent with gynecologic cancer surgery is safe and facilitates pelvic exposure in the morbidly obese patient. CASE: A 41-year-old morbidly obese female is diagnosed with recurrent adenocarcinoma of the cervix and has previously been treated with teletherapy and brachytherapy. She undergoes an anterior pelvic exenteration for curative intent. CONCLUSION: Panniculectomy at the time of pelvic exenteration is feasible. Morbidly obese patients with recurrent cervical cancer after treatment with pelvic radiation should be considered candidates for curative surgery.