Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression.

Prostate cancer progression to the lethal metastatic castration-resistant phenotype (mCRPC) is driven by αv integrins and is associated with Golgi disorganization and activation of the ATF6 branch of unfolded protein response (UPR). Overexpression of integrins requires N-acetylglucosaminyltransferase-V (MGAT5)-mediated glycosylation and subsequent cluster formation with Galectin-3 (Gal-3). However, the mechanism underlying this altered glycosylation is missing. For the first time, using HALO analysis of IHC, we found a strong association of integrin αv and Gal-3 at the plasma membrane (PM) in primary prostate cancer and mCRPC samples. We discovered that MGAT5 activation is caused by Golgi fragmentation and mislocalization of its competitor, N-acetylglucosaminyltransferase-III, MGAT3, from Golgi to the endoplasmic reticulum (ER). This was validated in an ethanol-induced model of ER stress, where alcohol treatment in androgen-refractory PC-3 and DU145 cells or alcohol consumption in patient with prostate cancer samples aggravates Golgi scattering, activates MGAT5, and enhances integrin expression at PM. This explains known link between alcohol consumption and prostate cancer mortality. ATF6 depletion significantly blocks UPR and reduces the number of Golgi fragments in both PC-3 and DU145 cells. Inhibition of autophagy by hydroxychloroquine (HCQ) restores compact Golgi, rescues MGAT3 intra-Golgi localization, blocks glycan modification via MGAT5, and abrogates delivery of Gal-3 to the cell surface. Importantly, the loss of Gal-3 leads to reduced integrins at PM and their accelerated internalization. ATF6 depletion and HCQ treatment synergistically decrease integrin αv and Gal-3 expression and temper orthotopic tumor growth and metastasis. IMPLICATIONS: Combined ablation of ATF6 and autophagy can serve as new mCRPC therapeutic.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Pathology Data-Based Risk Group Stratification Is Equivalent to That Obtained by Oncotype DX Testing in Prostatic Adenocarcinoma.

CONTEXT.­: Low-risk (Gleason score 3 + 3 = 6) and intermediate-risk (Gleason score 3 + 4 = 7) prostate carcinoma cases diagnosed on needle biopsies are frequently referred for gene expression studies such as Oncotype DX to help validate the risk. Risk assessment helps in determining prognosis and therapeutic decision making. OBJECTIVE.­: To determine if addition of molecular testing is necessary, by evaluating its correlation with risk stratification provided by pathology report (Gleason score, Grade Group, proportion of positive cores) and serum prostate-specific antigen (PSA) level. DESIGN.­: Our institutional database was searched for cases that had Oncotype DX testing after prostate biopsy. The final risk category determined by molecular testing was compared to the risk stratification predicted by the pathology report and serum PSA levels. Cases were classified as concordant if they fell under the same National Comprehensive Cancer Network risk and recommended initial therapy group. Follow-up information on discordant cases was obtained and used to determine if risk stratification by molecular testing was superior to that obtained from the clinicopathologic data. RESULTS.­: A total of 4967 prostate biopsies (2015-2020) were screened. Of these, 131 prostate carcinoma cases (2.6%) had Oncotype DX testing and 111 of 131 cases (85%) had follow-up information. There was risk stratification concordance in 93 of 111 cases (84%). All 18 of 111 cases (16%) that were discordant had a follow-up course that matched the risk predicted by pathology data and serum PSA. CONCLUSIONS.­: Risk stratification provided by information in the pathology report on routine biopsy assessment coupled with the serum PSA level is equivalent to that obtained by Oncotype DX testing.

Effects of the 2012 and 2018 US preventive services task force prostate cancer screening guidelines on pathologic outcomes after prostatectomy.

BACKGROUND: In May 2018, the US Preventive Services Task Force (USPSTF) recommended prostate cancer (PCa) screening for ages 55-69 be an individual decision. This changed from the USPSTF's May 2012 recommendation against screening for all ages. The effects of the 2012 and 2018 updates on pathologic outcomes after prostatectomy are unclear. METHODS: This study included 647 patients with PCa who underwent prostatectomy at our institution from 2005 to 2018. Patient groups were those diagnosed before the 2012 update (n = 179), between 2012 and 2018 updates (n = 417), and after the 2018 update (n = 51). We analyzed changes in the age of diagnosis, pathologic Gleason grade group (pGS), pathologic stage, lymphovascular invasion (LVI), and favorable/unfavorable pathology. Multivariable logistic regression adjusting for pre-biopsy covariables (age, prostate-specific antigen [PSA], African American race, family history) assessed impacts of 2012 and 2018 updates on pGS and pathologic stage. A p  < 0.05 was statistically significant. RESULTS: Median age increased from 60 to 63 (p = 0.001) between 2012 and 2018 updates and to 64 after the 2018 update. A significant decrease in pGS1, pGS2, pT2, and favorable pathology (p < 0.001), and a significant increase in pGS3, pGS4, pGS5, pT3a, and unfavorable pathology (p < 0.001) was detected between 2012 and 2018 updates. There was no significant change in pT3b or LVI between 2012 and 2018 updates. On multivariable regression, diagnosis between 2012 and 2018 updates was significantly associated with pGS4 or pGS5 and pT3a (p < 0.001). Diagnosis after the 2018 update was significantly associated with pT3a (p = 0.005). Odds of pGS4 or pGS5 were 3.2× higher (p < 0.001) if diagnosed between 2012 and 2018 updates, and 2.3× higher (p = 0.051) if after the 2018 update. Odds of pT3a were 2.4× higher (p < 0.001) if diagnosed between 2012 and 2018 updates and 2.9× higher (p = 0.005) if after the 2018 update. CONCLUSIONS: The 2012 USPSTF guidelines negatively impacted pathologic outcomes after prostatectomy. Patients diagnosed between 2012 and 2018 updates had increased frequency of higher-risk PCa and lower frequency of favorable disease. In addition, data after the 2018 update demonstrate a continued negative impact on postprostatectomy pathology. Thus, further investigation of the long-term effects of the 2018 USPSTF update is warranted.

The non-canonical mechanism of ER stress-mediated progression of prostate cancer.

BACKGROUND: The development of persistent endoplasmic reticulum (ER) stress is one of the cornerstones of prostate carcinogenesis; however, the mechanism is missing. Also, alcohol is a physiological ER stress inducer, and the link between alcoholism and progression of prostate cancer (PCa) is well documented but not well characterized. According to the canonical model, the mediator of ER stress, ATF6, is cleaved sequentially in the Golgi by S1P and S2P proteases; thereafter, the genes responsible for unfolded protein response (UPR) undergo transactivation. METHODS: Cell lines used were non-malignant prostate epithelial RWPE-1 cells, androgen-responsive LNCaP, and 22RV1 cells, as well as androgen-refractory PC-3 cells. We also utilized PCa tissue sections from patients with different Gleason scores and alcohol consumption backgrounds. Several sophisticated approaches were employed, including Structured illumination superresolution microscopy, Proximity ligation assay, Atomic force microscopy, and Nuclear magnetic resonance spectroscopy. RESULTS: Herein, we identified the trans-Golgi matrix dimeric protein GCC185 as a Golgi retention partner for both S1P and S2P, and in cells lacking GCC185, these enzymes lose intra-Golgi situation. Progression of prostate cancer (PCa) is associated with overproduction of S1P and S2P but monomerization of GCC185 and its downregulation. Utilizing different ER stress models, including ethanol administration, we found that PCa cells employ an elegant mechanism that auto-activates ER stress by fragmentation of Golgi, translocation of S1P and S2P from Golgi to ER, followed by intra-ER cleavage of ATF6, accelerated UPR, and cell proliferation. The segregation of S1P and S2P from Golgi and activation of ATF6 are positively correlated with androgen receptor signaling, different disease stages, and alcohol consumption. Finally, depletion of ATF6 significantly retarded the growth of xenograft prostate tumors and blocks production of pro-metastatic metabolites. CONCLUSIONS: We found that progression of PCa associates with translocation of S1P and S2P proteases to the ER and subsequent ATF6 cleavage. This obviates the need for ATF6 transport to the Golgi and enhances UPR and cell proliferation. Thus, we provide the novel mechanistic model of ATF6 activation and ER stress implication in the progression of PCa, suggesting ATF6 is a novel promising target for prostate cancer therapy.

Optimal PSA Threshold for Obtaining MRI-Fusion Biopsy in Biopsy-Naïve Patients.

OBJECTIVE: The study investigates the prostate-specific antigen threshold for adding targeted, software-based, magnetic resonance imaging-ultrasound fusion biopsy during a standard 12-core biopsy in biopsy-naïve patients. It secondarily explores whether the targeted biopsy is necessary in setting of abnormal digital rectal examination. METHODS: 260 patients with suspected localized prostate cancer with no prior biopsy underwent prostate magnetic resonance imaging and were found to have Prostate Imaging Reporting and Data System score ≥ 3 lesion(s). All 260 patients underwent standard 12-core biopsy and targeted biopsy during the same session. Clinically significant cancer was Gleason ≥3 + 4. RESULTS: Percentages of patients with prostate-specific antigen 0-1.99, 2-3.99, 4-4.99, 5-5.99, 6-9.99, and ≥10 were 3.0%, 4.7%, 20.8%, 16.9%, 37.7%, and 16.9%, respectively. Cumulative frequency of clinically significant prostate cancer increased with the addition of targeted biopsy compared with standard biopsy alone across all prostate-specific antigen ranges. The difference in clinically significant cancer detection between targeted plus standard biopsy compared to standard biopsy alone becomes statistically significant at prostate-specific antigen >4.3 (p=0.031). At this threshold, combination biopsy detected 20 clinically significant prostate cancers, while standard detected 14 with 88% sensitivity and 20% specificity. Excluding targeted biopsy in setting of a positive digital rectal exam would save 12.3% magnetic resonance imaging and miss 1.8% clinically significant cancers in our cohort. CONCLUSIONS: In biopsy-naïve patients, at prostate-specific antigen >4.3, there is a significant increase in clinically significant prostate cancer detection when targeted biopsy is added to standard biopsy. Obtaining standard biopsy alone in patients with abnormal digital rectal examinations would miss 1.8% clinically significant cancers in our cohort.

APE1 and SSRP1 is overexpressed in muscle invasive bladder cancer and associated with poor survival.

BACKGROUND: Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) plays a critical role in DNA base excision repair (BER) pathway and has been reported to be overexpressed in multiple cancers. Previously, we have shown that histone chaperone FACT complex (Facilitates Chromatin Transcription, a heterodimer of SSRP1 and SPT16 proteins) facilitates the chromatin access and DNA repair function of APE1, and their expression levels are correlated with promoting drug resistance in cancer. FACT inhibitor has been introduced in phase I and II clinical trials for chemosensitization of advanced solid cancers. However, the expression profile and prognostic significance of APE1 and FACT complex in bladder cancer remains largely unknown. METHODS: Retrospectively, 69 bladder cancer samples were retrieved and submitted for immunohistochemical staining of APE1 and SSRP1. Expression profile including cytoplasmic and nuclear staining of APE1 and expression level of SSRP1 was examined and semi-quantified to render a H-score. The prognostic significance of APE1 and SSRP1 was evaluated by Kaplan-Meier survival analysis in our cohort and R2 database. RESULTS: APE1 expression is elevated in bladder cancer compared to normal adjacent tissues. Compared with low grade tumors, high grade tumors show a shift in the staining pattern including higher intensity and positive cytoplasmic staining. Carcinoma in situ has a similar staining pattern to high grade tumors. APE1 and SSRP1 staining intensity increases as tumor progresses with stage. There is a correlation between APE1 and SSRP1 staining in invasive bladder cancer (Spearman r = 0.5466, p < 0.0001). The increased expression of APE1 and SSRP1 is associated with poor survival in Kaplan-Meier analysis in our cohort and in R2-TCGA bladder cancer database. CONCLUSIONS: The expression levels of APE1 and SSRP1 are significantly elevated in bladder cancer as compared to normal adjacent tissues. APE1 correlates with SSRP1 expression in high grade tumors. Overexpression of APE1 and SSRP1 is associated with poor survival in bladder cancer. This suggests the usage of FACT inhibitor curaxins in muscle invasive bladder cancer to target FACT complex and APE1 to improve chemosensitization after further validation.

The Positive Effect of Monetary Incentive on Urology Resident Research.

OBJECTIVE: To evaluate whether a financial incentive changed research patterns among residents over a 12-year period. METHODS: At our institution, beginning July 2016, any resident work that led to a PubMed citation was awarded $1,000. A review of the PubMed database and the regional meeting of the South Central Section of AUA (SCS/AUA) presentation itineraries were used to quantify and qualify the participation in research by these residents before and after introduction of the financial incentive. RESULTS: Scholarly activity from thirty out of thirty possible residents was evaluated. The monetary incentive resulted in increased production post-incentive (6.33) vs pre-incentive (2.44) in average total authorship participation published to PubMed per year (P = .0125). The average number of PubMed primary authorships per resident per year increased from 0 in July 2007-June 2008 to 0.7 in July 2018-June 2019, displaying upward trajectory. Average primary authorship of research produced per year presented at SCS/AUA and published to PubMed increased postincentive (9.00) vs pre-incentive (4.89) (P = .0479). More review articles and less basic science research were published after the incentive. CONCLUSION: Offering financial incentives to urology residents increased publications and meaningful participation in research.

The Role of Alcohol-Induced Golgi Fragmentation for Androgen Receptor Signaling in Prostate Cancer.

Multiple epidemiologic observations and meta-analysis clearly indicate the link between alcohol abuse and the incidence and progression of prostate cancer; however, the mechanism remains enigmatic. Recently, it was found that ethanol (EtOH) induces disorganization of the Golgi complex caused by impaired function of the largest Golgi matrix protein, giantin (GOLGB1), which, in turn, alters the Golgi docking of resident Golgi proteins. Here, it is determined that in normal prostate cells, histone deacetylase 6 (HDAC6), the known regulator of androgen receptor (AR) signaling, localizes in the cytoplasm and nucleus, while its kinase, glycogen synthase kinase ß (GSK3ß), primarily resides in the Golgi. Progression of prostate cancer is accompanied by Golgi scattering, translocation of GSK3ß from the Golgi to the cytoplasm, and the cytoplasmic shift in HDAC6 localization. Alcohol dehydrogenase-generated metabolites induces Golgi disorganization in androgen-responsive LNCaP and 22Rv1 cells, facilitates tumor growth in a mouse xenograft model and activates anchorage-independent proliferation, migration, and cell adhesion. EtOH-treated cells demonstrate reduced giantin and subsequent cytoplasmic GSK3ß; this phenomenon was validated in giantin-depleted cells. Redistribution of GSK3ß to the cytoplasm results in phosphorylation of HDAC6 and its retention in the cytoplasm, which, in turn, stimulates deacetylation of HSP90, AR import into the nucleus, and secretion of prostate-specific antigen (PSA). Finally, the relationship between Golgi morphology, HDAC6 cytoplasmic content, and clinicopathologic features was assessed in human prostate cancer patient specimens with and without a history of alcohol dependence. IMPLICATIONS: This study demonstrates the importance of alcohol-induced Golgi fragmentation in the activation of AR-mediated proliferation.

Safety and Clinical Outcomes of Robot-Assisted Radical Prostatectomy in Kidney Transplant Patients: A Systematic Review.

OBJECTIVE: To evaluate the safety and outcomes of robot-assisted radical prostatectomy (RARP) in renal transplant recipients (RTRs) based on available literature. MATERIALS AND METHODS: A literature search was performed using PubMed, Embase, and Web of Science through "robot" AND "prostatectomy" AND "transplant." Three authors separately reviewed the records to select the relevant articles with any discrepancies solved by open discussion. Patient age, prostate-specific antigen, Gleason score, and tumor stage were recorded as well as intraoperative and postoperative complications, length of stay, surgical margin status, and disease recurrence, if provided. The operative techniques and modification/adjustments to standard port placements were also reviewed. We also include our case report in this review. RESULTS: We retrieved 10 articles reporting clinical data on RARP for kidney transplant patients, including 5 case series (level 4) and 5 case reports (level 4). A total of 35 kidney transplant recipients undergoing RARP were analyzed in this systematic review, one case in our institution included. None of the cases had major technical difficulties precluding the operation. Technical modifications to the standard technique were described in 10 of the 11 articles specifically including modifications to port placement (54% of patients), development of the space of Retzius (60% of patients), and performance of lymphadenectomy. Mean operative time was 220 minutes. Perioperative complication rate was 17.1% (6 of 35 patients), with only one Clavien III or greater complication. The rate of positive surgical margins was found to be 31.4%. Data on biochemical recurrence revealed a combined rate of 18.1%. CONCLUSIONS: RARP is technically feasible for treating localized prostate cancer in RTRs. Graft function did not deteriorate in any patient. Modifications to the standard technique should be considered specifically for port placement, development of the space of Retzius, and performance of lymphadenectomy. Oncologic outcomes remain difficult to interpret given the small number of reported cases.

Hyaluronic acid formulation of near infrared fluorophores optimizes surgical imaging in a prostate tumor xenograft.

The presence of positive surgical margins confers an increased risk of biochemical relapse and need for salvage therapy in men undergoing radical prostatectomy. Image-guided surgery using near-infrared (NIR) fluorescent contrast agents is a potential method to detect remaining cancerous tissue. The objective of this study was to evaluate three hyaluronic acid (HA) nanoparticle (NP) formulations loaded with NIR fluorophore for their ability to contrast-enhance prostate cancer. HA was modified by conjugation with the hydrophobic ligand, aminopropyl-1-pyrenebutanamide to drive nanoparticle self-assembly. Indocyanine green (ICG) was physicochemically entrapped in the HA-NP, termed NanoICG. Alternatively, Cy7.5 was directly conjugated to amphiphilic HA, termed NanoCy7.5. NanoCy7.5 was synthesized with two HA molecular weights to determine the HA size contribution to delivery to PC3 prostate tumor xenografts. Contrast-enhancement of the tumors and relative biodistribution were assessed by a series of fluorescence imaging, image-guided surgery with spectroscopy, and microscopic techniques. Intravenously administered NanoICG improved tumor signal-to-noise ratio (SNR) at 24 h over ICG by 2.9-fold. NanoCy7.5 with 10 kDa and 100 kDa HA improved tumor SNR by 6.6- and 3.1-fold over Cy7.5 alone, respectively. The PC3 xenograft was clearly identified with the image-guided system providing increased contrast enhancement compared to surrounding tissue for NanoICG and NanoCy7.5 with 10 kDa HA. NIR fluorescence microscopy showed that Cy7.5 in NPs with 10 kDa HA were distributed throughout the tumor, while NanoCy7.5 with 100 kDa HA or NanoICG delivered dye mainly to the edge of the tumor. CD31 staining suggested that PC3 tumors are poorly vascularized. These studies demonstrate the efficacy of a panel of HA-derived NPs in identifying prostate tumors in vivo, and suggest that by tuning the structural properties of these NPs, optimized delivery can be achieved to poorly vascularized tumors. STATEMENT OF SIGNIFICANCE: We have demonstrated the potential of a panel of near-infrared fluorescent (NIRF) nanoparticles (NPs) for image-guided surgery in a prostate cancer xenograft model. Image-guided surgery and imaging of organs ex vivo showed greater tumor signal and contrast when mice were administered NIRF dyes that were covalently conjugated to (NanoCy7.510k-PBA) or physicochemically entrapped in (NanoICGPBA) hyaluronic acid (HA) NPs, compared to free dyes. These results show the potential to use these NPs as tools to detect the margins of tumors and to differentiate healthy and tumor tissue intraoperatively. Moreover, this project provides insight into selecting optimal formulation strategies for poorly vascularized tumors.

Risk of continuous bladder irrigation in the monoplace hyperbaric chamber: a cautionary tale.

We previously published our method of performing continuous bladder irrigation (CBI) in a monoplace hyperbaric chamber [1]. This method entailed the use of an IV pump to infuse saline into the monoplace chamber. The specter of causing iatrogenic rupture of the bladder was raised following such a case, reported herein, of a woman with hemorrhagic radiation cystitis leading to cystectomy. Due to the danger of bladder rupture while providing CBI with a pump, we retract ourpreviously reported method and encourage the use of either a gravity-fed system or delay in hyperbaric oxygen therapy treatment until CBI is no longer necessary.

Delayed severe anaphylactoid reaction following retrograde pyelogram: A case report.

Retrograde pyelography is used to evaluate upper collecting system in patients with hematuria who have contrast allergy. Reported here is a patient who developed severe, late-onset anaphylactoid reaction after retrograde pyelography. Premedication is commonly used to reduce risk of allergic reaction but has limited evidence to support its efficacy. Caution should be used when evaluating microhematuria with retrograde pyelography in patients with prior anaphylactoid reaction to intravenous contrast.

Carcinosarcoma of the Tunica Vaginalis Following Radiation Therapy for Localized Prostate Cancer.

Spermatic cord tumors (SCTs) are rare neoplasms with 80% exhibiting benign pathology. Of the malignant SCTs, 90% are sarcomas. To date there has only been one documented case of primary CS of the spermatic cord which occurred in a 40 year old with no reported medical history. A 76-year-old male with a history of biopsy proven Gleason score 7 (3 + 4) prostatic adenocarcinoma underwent external beam radiation therapy (7920 cGy) in 44 fractions in 2004. He presented with a 3 year history of an asymptomatic right hydrocele. Several scrotal ultrasounds had been performed confirming a hydrocele, with the most recent revealing a hydrocele measuring 10 × 14 cm and several epididymal cysts. During the hydrocelectomy a firm suspicious mass was noted inside the tunica vaginalis and involving the spermatic cord. Given the intraoperative findings, decision was made to proceed with radical orchiectomy. Final pathologic examination revealed the tumor to have a biphasic pattern composed of spindled cells and also cells with an epithelioid morphology. Five months following orchiectomy he patient presented with a painful, enlarging right upper scrotal mass. A CT scan revealed new soft tissue lesions suspicious for necrotic lymph nodes within the right inguinal canal. Additional metastatic evaluation revealed multiple new pleural and parenchymal lung nodules. CT guided needle biopsy of a left lung nodule demonstrated spindle cells with high cellularity and areas of necrosis which were histomorphologically similar to the previous scrotal CS. Gemcitabine therapy was subsequently started. Four months following the diagnosis of metastatic CS, the patient expired. Dedifferentiation of prostatic adenocarcinoma to prostatic CS should be considered as a treatment outcome after localized radiation therapy to the prostate due to the highly aggressive nature of metastatic CS.

Kinematic and ergonomic assessment of laparoendoscopic single-site surgical instruments during simulator training tasks.

While laparoendoscopic single-site surgery (LESS) appears to be feasible and safe, instrument triangulation, tissue handling, and other bimanual tasks are difficult even for experienced surgeons. Novel technologies emerged to overcome LESS' procedural and ergonomic difficulties of "tunnel vision" and "instrument clashing." Surgeon kinematics, self-reported workload and upper body discomfort were used to compare straight, bent and two articulating instruments while performing two basic surgical tasks in a LESS simulator. All instruments resulted in bilateral elevation and rotation of the shoulders, excessive forearm motion and flexion and ulnar deviation of wrists. Surgeons' adopted non-neutral upper extremity postures and performed excessive joint excursions to compensate for reduced freedom of movement at the single insertion site and to operate the instrument mechanisms. LESS' cosmetic benefits continue to impact laparoscopic surgery and by enabling performance through improved instruments, ergonomic improvement for LESS can reduce negative impact on surgeon well-being and patient safety.

Lymphoepithelioma-like, a variant of urothelial carcinoma of the urinary bladder: a case report and systematic review for optimal treatment modality for disease-free survival.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare high-grade carcinoma that resembles nasopharyngeal lymphoepithelioma and can occur throughout the body. First reported in 1991, bladder LELC has an incidence of about 1% of all bladder carcinomas. Due to its rare occurrence, prognoses and ideal treatment guidelines have not been clearly defined. METHODS: A PubMed search was performed using two terms, "lymphoepithelioma-like carcinoma" and "bladder." Review articles, articles in foreign languages, expression studies, and studies not performed in the bladder were excluded. We report a case of LELC of the bladder including treatment and outcome and performed a systematic review of all 36 available English literatures from 1991 to 2016 including the present case to identify factors affecting disease-free survival. RESULTS: One hundred forty cases of bladder LELC were analyzed. The mean age of the patients was 70.1 years ranging from 43 to 90 years with 72% males and 28% females. Pure LELC occurs most often at 46% followed by mixed LELC 28% and predominant LELC 26%. EBV testing was negative in all cases tested. Mean follow-up length for all cases was 33.8 months with no evidence of disease in 62.2%, while 11.1% died of disease, 10.4% alive with metastasis, and 8.2% died without disease. 5.0% of cases had recurrence at an average of 31.3 months. Prognosis is significantly favorable for patients presenting with pure or predominant forms of LELC compared to mixed type (p < 0.0001). The treatment significantly associated with the highest disease mortality and lowest disease-free survival was TURBT alone when compared to any multi-modality treatment (p < 0.01). CONCLUSION: We conclude that the best treatment modality associated with the highest disease-free survival is multi-modal treatment including radical cystectomy.

Preoperative frailty predicts postoperative complications and mortality in urology patients.

PURPOSE: Our objective was to determine the impact of preoperative frailty, as measured by validated Risk Analysis Index (RAI), on the occurrence of postoperative complications after urologic surgeries in a national database comprised of diverse practice groups and cases. STUDY DESIGN: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2011 for a list of abdominal, vaginal, transurethral and scrotal urological surgeries using Current Procedural Terminology codes. The study population was subdivided into two groups based on the nature of procedures performed: complex procedures (inpatient) and simple procedures (outpatient). Risk Analysis Index score was calculated using preoperative NSQIP variables to determine preoperative frailty. Major postoperative morbidities (pulmonary, cardiovascular, renal and infectious), mortality, return to operating room, discharge destination and readmission to the hospital were examined. RESULTS: The study identified 42,715 patients who underwent urological procedures, 25,693 complex and 17,022 simple procedures. Mean RAI score (range) was 7.75 (0-53). The majority of patients scored low on the RAI (90.57 % with RAI < 10). As the RAI score increased, there was a significant increase in postoperative complication and mortality rate (both p < 0.0001). Similarly, the rate of return to operating room and hospital readmission rate increased as RAI increased (both p < 0.0001). Additionally, rate of discharge to home decreased. Interestingly, mortality rate in patients with high RAI did not differ comparing simple to complex procedures (p = 0.90), whereas complications were significantly greater in the complex operation (p = 0.01). CONCLUSIONS: Increase in frailty, as measured by RAI score, is associated with increased postoperative complications and mortality. RAI may allow for rapid identification and counseling of patients who are at high risk of adverse perioperative outcomes.

Does endorectal coil MRI increase the accuracy of preoperative prostate cancer staging?

INTRODUCTION: We sought to investigate the association of preprostatectomy magnetic resonance imaging (MRI) and surgical pathologic findings in patients with prostate cancer. MATERIALS AND METHODS: All patients with prostate cancer and preprostatectomy MRI available between 2002 and 2015 were included. Age, prostate-specific antigen at diagnosis, Gleason score at biopsy, MRI technique, radiology report suggestive of prostate cancer, extraprostatic invasion and seminal vesicle involvement, lymphadenopathy and final pathology report were retrospectively reviewed. Data was analyzed for sensitivity, specificity, positive and negative predictive values of MRI findings for predicting T3 disease. Consistency of MRI findings with pathology report was compared between MRIs with or without endorectal coil (ERC). RESULTS: A cohort of 83 patients was identified. Eighty-seven percent of the patients had MRI findings suggestive of prostate cancer. MRI was performed with and without ERC in 21 (25.3%) and 62 (74.3%) patients respectively. Eighty-five percent of patients with ERC and 88.7% of those without ERC had MRI findings suggestive of prostate cancer (p = 0.659). MRI correlated with final surgical pathology stage T3 in 53 patients (64%). MRI findings were consistent with final pathology report in 70% of ERC group and 61.3% of non ERC group (p = 0.482). In terms of extra prostatic invasion or seminal vesicle involvement, MRI had specificity, sensitivity, positive and negative predictive values of 84.44%, 37.84%, 66.67% and 62.3% respectively. CONCLUSIONS: MRI was specific but not sensitive in determining extraprostatic or seminal vesicle invasion. MRI was not accurate for lymph node involvement. In addition, using an ERC did not increase the accuracy of prostate MRI in this small cohort.

Lunar Phases and Emergency Department Visits for Renal Colic Due to Ureteral Calculus.

BACKGROUND: Urolithiasis affects an estimated 5% of the population and the lifetime risk of passing a stone in the urinary tract is estimated to be 8-10%. Urinary calculus formation is highly variable and while certain risk factors such as age, gender, seasonality, anatomic abnormality, and metabolic diseases have been identified, not much is known regarding the association of environmental factors such as lunar phases on renal colic. We conducted a retrospective study to test the hypothesis that full moon phase is an environmental factor associated for increased emergency department (ED) visits for renal colic due to ureteral calculus. METHODS: We analyzed 559 renal colic diagnoses by the ED at the University of Nebraska Medical Center in a 24-month period and compared them with corresponding lunar phases as well as supermoon events. The lunar phases were defined as full moon ± two days, new moon ± two days, and the days in-between as normal days according to the lunar calendar. Supermoon event dates were obtained from NASA. RESULTS: 90 cases (16.1%) were diagnosed during full moon phase, 89 cases (15.9%) were diagnosed during new moon phase, and 380 cases (68.0%) were diagnosed during normal days. The incidence of renal colic showed no statistically significant association with lunar phases or supermoon events. CONCLUSION: In this retrospective longitudinal study with adequate power, neither full moon phase nor supermoon event exhibited an association with increased renal colic diagnoses due to ureteral calculus by the ED at the University of Nebraska Medical Center.