Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

OBJECTIVES: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal. BACKGROUND: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed. METHODS: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply. RESULTS: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess. CONCLUSIONS: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons.

Diet Quality and Survival in a Population-Based Bladder Cancer Study.

Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.

Do commonly used prostate medications alter prostate MRI and fusion biopsy performance?

AIMS: To determine whether phosphodiesterase inhibitors (PDEi) or α-antagonists (AA) were associated with differences in region of interest (ROI) characteristics or prostate cancer detection on fusion biopsy (FB). MATERIALS AND METHODS: Records from 847 consecutive patients undergoing FB at three separate institutions over a period of 2 years were retrospectively reviewed. Associations between medication use, Prostate Imaging Reporting & Data System (PIRADS) scores, and ROI locations were assessed with ordinal logistic regression. Associations with lesion size and International Society of Urologic Pathology (ISUP) grade group (GG) on biopsy were tested using multivariate regression. RESULTS: Medication use included PDEi in 14.2% and AA in 23.0%. PDEi use was associated with 19.3% smaller lesion diameter (-2.8 mm; CI from -4.8 to -0.7; p < 0.01) and lower PIRADS scores on MRI (OR 0.60; CI 0.40 - 1.00; p = 0.05). AA use was associated with higher PIRADS scores (OR 1.43; CI 0.97 - 2.11; p = 0.06), fewer positive fusion-directed biopsy cores (-28.6%, CI from -57.9 to 0.01%, p = 0.05), and downgrading on final pathology (-19%; CI from -40 to 2%; p = 0.06). CONCLUSION: For PIRADS scores ≥ 3, PDEi use is associated with smaller ROI and lower PIRADS scores, while AA use is associated with higher PIRADS scores. Neither medication was associated with differences in biopsy GG. Prospective studies are needed to investigate the discordance between multi-parametric magnetic resonance imaging (mpMRI) results and oncologic outcomes associated with PDEi and AA use.

Parastomal hernia development after cystectomy and ileal conduit for bladder cancer: results from the Dartmouth ileal conduit enhancement (DICE) project.

INTRODUCTION Limited information exists regarding parastomal hernia development in bladder cancer patients. The purpose of this investigation was to describe the natural history of parastomal hernias and identify risk factors for hernia development in patients who undergo cystectomy with ileal conduit urinary diversion. MATERIALS AND METHODS: A retrospective cohort study was performed of bladder cancer patients who underwent cystectomy with ileal conduit urinary diversion between January 1st 2009 and July 31st 2018 at Dartmouth-Hitchcock Medical Center. The primary outcome of interest was the presence of a parastomal hernia as evident on postoperative cross-sectional imaging obtained for disease surveillance. RESULTS: A total of 107 patients were included with a mean age of 70.9 years and 29.9% being female. Parastomal hernias were identified in 68.2% of bladder cancer patients who underwent cystectomy with ileal conduit urinary diversion. Forty percent of patients with a parastomal hernia reported symptoms related to their hernia, while 12.5% underwent operative repair. After multivariate adjustment, patients with a postop body mass index (BMI) > 30 kg/m² (odds ratio [OR]: 21.8, 95% CI: 1.6-305.2) or stage III or IV bladder cancer (OR: 18, 95% CI: 2.1-157.5), had significantly greater odds of parastomal hernia development. Fifty percent of parastomal hernias were identified 1.3 years from surgery, while 75% were identified by 2 years after cystectomy. CONCLUSION: Parastomal hernias developed in over two-thirds of bladder cancer patients and occurred rapidly following cystectomy and ileal conduit urinary diversion. Greater postoperative BMI and bladder cancer stage were identified as significant risk factors for parastomal hernia development. Significant opportunity exists to reduce morbidity associated with parastomal hernias in this population.

The impact of frequent cystoscopy on surgical care and cancer outcomes among patients with low-risk, non-muscle-invasive bladder cancer.

BACKGROUND: Surveillance recommendations for patients with low-risk, non-muscle-invasive bladder cancer (NMIBC) are based on limited evidence. The objective of this study was to add to the evidence by assessing outcomes after frequent versus recommended cystoscopic surveillance. METHODS: This was a retrospective cohort study of patients diagnosed with low-risk (low-grade Ta (AJCC)) NMIBC from 2005 to 2011 with follow-up through 2014 from the Department of Veterans Affairs. Patients were classified as having undergone frequent versus recommended cystoscopic surveillance (>3 vs 1-3 cystoscopies in the first 2 years after diagnosis). By using propensity score-adjusted models, the authors estimated the impact of frequent cystoscopy on the number of transurethral resections, the number of resections without cancer in the specimen, and the risk of progression to muscle-invasive cancer or bladder cancer death. RESULTS: Among 1042 patients, 798 (77%) had more frequent cystoscopy than recommended. In adjusted analyses, the frequent cystoscopy group had twice as many transurethral resections (55 vs 26 per 100 person-years; P < .001) and more than 3 times as many resections without cancer in the specimen (5.7 vs 1.6 per 100 person-years; P < .001). Frequent cystoscopy was not associated with time to progression or bladder cancer death (3% at 5 years in both groups; P = .990). CONCLUSIONS: Frequent cystoscopy among patients with low-risk NMIBC was associated with twice as many transurethral resections and did not decrease the risk for bladder cancer progression or death, supporting current guidelines.

'Dr Google': trends in online interest in prostate cancer screening, diagnosis and treatment.

OBJECTIVES: To examine trends in online search behaviours related to prostate cancer on a national and regional scale using a dominant major search engine. MATERIALS AND METHODS: Google Trends was queried using the terms 'prostate cancer', 'prostate-specific antigen' (PSA), and 'prostate biopsy' between January 2004 and January 2019. Search volume index (SVI), a measure of relative search volume on Google, was obtained for all terms and examined by region and time period: pre-US Preventive Services Task Force (USPSTF) Grade D draft recommendation on PSA screening; during the active Grade D recommendation; and after publication of the recent Grade C draft recommendation. RESULTS: Online interest in PSA screening differed by time period (P < 0.01). The SVI for PSA screening was greater pre-Grade D draft recommendation (82.7) compared to during the recommendation (74.5), while the SVI for PSA screening was higher post-Grade C draft recommendation (90.4) compared to both prior time periods. Similar results were observed for prostate biopsy and prostate cancer searches. At the US state level, online interest in prostate cancer was highest in South Carolina (SVI 100) and lowest in Hawaii (SVI 64). For prostate cancer treatment options, online interest in cryotherapy, prostatectomy and prostate cancer surgery overall increased, while searches for active surveillance, external beam radiation, brachytherapy and high-intensity focused ultrasonography remained stable. CONCLUSION: Online interest in prostate cancer has changed over time, particularly in accordance with USPSTF screening guidelines. Google Trends may be a useful tool in tracking public interest in prostate cancer screening, diagnosis, and treatment, especially as it relates to major shifts in practice guidelines.

Acquired Hemophilia presenting as Gross Hematuria following Kidney Stone - A Case Report and Review of the Literature.

A rare condition in itself, acquired hemophilia A, seldom presents as isolated gross hematuria. It is a serious condition with a high mortality rate and thus clinical suspicion followed by prompt diagnosis is imperative (1). In fact, only 8 cases of such presentation of this condition have been reported thus far in the literature. Of these, none describe the initial presentation of hematuria with the inciting event of a kidney stone. We present a case of a 67-year-old man with signs and symptoms of nephrolithiasis accompanied by profuse hematuria, who was subsequently found to have developed expression of factor VIII inhibitor leading to acquired hemophilia A.

Assembling and validating data from multiple sources to study care for Veterans with bladder cancer.

BACKGROUND: Despite the high prevalence of bladder cancer, research on optimal bladder cancer care is limited. One way to advance observational research on care is to use linked data from multiple sources. Such big data research can provide real-world details of care and outcomes across a large number of patients. We assembled and validated such data including (1) administrative data from the Department of Veterans Affairs (VA), (2) Medicare claims, (3) data abstracted by tumor registrars, (4) data abstracted via chart review from the national electronic health record, and (5) full text pathology reports. METHODS: Based on these combined data, we used administrative data to identify patients with newly diagnosed bladder cancer who received care in the VA. To validate these data, we first compared the diagnosis date from the administrative data to that from the tumor registry. Second, we measured accuracy of identifying bladder cancer care in VA administrative data, using a random chart review (n = 100) as gold standard. Lastly, we compared the proportion of patients who received bladder cancer care among those who did versus did not have full text bladder pathology reports available, expecting that those with reports are significantly more likely to receive care in VA. RESULTS: Out of 26,675 patients, 11,323 (42%) had tumor registry data available. 90% of these patients had a difference of 90 days or less between the diagnosis dates from administrative and registry data. Among 100 patients selected for chart review, 59 received bladder cancer care in VA, 58 of which were correctly identified using administrative data (sensitivity 98%, specificity 90%). Receipt of bladder cancer care was substantially more common among those who did versus did not have bladder pathology available (96% vs. 43%, p < 0.001). CONCLUSION: Merging administrative with electronic health record and pathology data offers new possibilities to validate the use of administrative data in bladder cancer research.

Qualitative insights into how men with low-risk prostate cancer choosing active surveillance negotiate stress and uncertainty.

BACKGROUND: Active surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach. METHODS: Thematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance. RESULTS: The decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress. CONCLUSIONS: Support systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline.

PURPOSE: Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients' rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC. MATERIALS AND METHODS: A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions.(1) RESULTS: A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient's response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C. CONCLUSION: The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.

MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer.

BACKGROUND: MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. METHODS: We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between media. RESULTS: Numerous microRNAs were detected and overlapping from specific bio-specimen sources. MiR-4454 and miR-21 overexpression was found in three sources: tumor, WBCs and urine. Additionally, miR-15b-5p, miR-126-3p, miR-93-5p, and miR-150-5p were common to tumor/WBCs, while miR-720/3007a, miR-205, miR-200c-3p and miR-29b-3p common to tumor/urine. Significant associations were noted between the log-adjusted average miRNA counts in tumor vs. WBCs (r = 0.418 p < 0.001), and tumor vs. urine (r = 0.38 p < 0.001). No association was seen tumor vs. plasma exosome miRs (r = 0.07 p = 0.06). CONCLUSIONS: MicroRNA profiling from matched samples in patients shows a significant number of microRNAs up regulated in bladder tumors are identifiable in urine exosomes and WBCs of the same patient, but not in blood plasma. This study demonstrated varying relationships between miRNA detected in biological media from the same patient, and serves to inform the potential of urine-based microRNAs as biomarkers for bladder cancer and potentially other malignancies.

Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence.

Bladder cancer is the fourth most common cancer among men in the United States and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA-34a (miR-34a) is a short noncoding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population-based prognostic study of bladder cancer in New Hampshire, United States to evaluate miR-34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long-term for recurrence, progression and survival. Fluorescence-based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (n = 229). A larger proportion of the nonmuscle invasive tumors had high levels of miR-34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR-34a levels in their baseline nonmuscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio 0.57, 95% confidence interval 0.34-0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR-34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR-34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder.

Immunoglobulin G4-related disease in the urinary bladder.

Immunoglobulin G4-related disease is a fibroinflammatory condition of unclear etiology that can present with inflammatory changes and enlargement of a wide variety of organs, most commonly in the gastrointestinal tract. A diagnosis requires an elevated serum immunoglobulin G4 concentration and a tissue biopsy showing a dense plasma cell infiltrate with an increased percentage of immunoglobulin G4+ plasma cells. This disease infrequently presents in the genitourinary tract, and as such might be unfamiliar to and potentially overlooked by urologists. Here we present the third reported case of immunoglobulin G4-related disease manifesting as a mass in the urinary bladder.

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.

Background: Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. Methods: DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering. Results: Immune hot and cold groups had different immune compositions in the TME but not in circulating blood. Two clusters of patients identified with consensus clustering had different immune compositions not only in the TME but also in blood. Conclusion: Detailed immune profiling via methylation cytometry reveals the significance of understanding tumor and systemic immune relationships in cancer patients.

Bladder cancer and treatment outcomes depend on the immune profiles in the tumor and blood. Our study, using DNA methylation cytometry, measured immune cell proportions in both areas. Patients were grouped based on immune status and consensus clustering. Results showed distinct immune compositions in the tumor, but not in blood, for hot and cold groups. Consensus clustering revealed two patient clusters with differing immune compositions in both tumor and blood. This detailed immune profiling highlights the importance of understanding the complex interplay between tumor and systemic immunity in bladder cancer patients.

Genome-Scale Methylation Analysis Identifies Immune Profiles and Age Acceleration Associations with Bladder Cancer Outcomes.

BACKGROUND: Immune profiles have been associated with bladder cancer outcomes and may have clinical applications for prognosis. However, associations of detailed immune cell subtypes with patient outcomes remain underexplored and may contribute crucial prognostic information for better managing bladder cancer recurrence and survival. METHODS: Bladder cancer case peripheral blood DNA methylation was measured using the Illumina HumanMethylationEPIC array. Extended cell-type deconvolution quantified 12 immune cell-type proportions, including memory, naïve T and B cells, and granulocyte subtypes. DNA methylation clocks determined biological age. Cox proportional hazards models tested associations of immune cell profiles and age acceleration with bladder cancer outcomes. The partDSA algorithm discriminated 10-year overall survival groups from clinical variables and immune cell profiles, and a semi-supervised recursively partitioned mixture model (SS-RPMM) with DNA methylation data was applied to identify a classifier for 10-year overall survival. RESULTS: Higher CD8T memory cell proportions were associated with better overall survival [HR = 0.95, 95% confidence interval (CI) = 0.93-0.98], while higher neutrophil-to-lymphocyte ratio (HR = 1.36, 95% CI = 1.23-1.50), CD8T naïve (HR = 1.21, 95% CI = 1.04-1.41), neutrophil (HR = 1.04, 95% CI = 1.03-1.06) proportions, and age acceleration (HR = 1.06, 95% CI = 1.03-1.08) were associated with worse overall survival in patient with bladder cancer. partDSA and SS-RPMM classified five groups of subjects with significant differences in overall survival. CONCLUSIONS: We identified associations between immune cell subtypes and age acceleration with bladder cancer outcomes. IMPACT: The findings of this study suggest that bladder cancer outcomes are associated with specific methylation-derived immune cell-type proportions and age acceleration, and these factors could be potential prognostic biomarkers.

Ureteroscopic biopsy of upper tract urothelial carcinoma using a novel ureteroscopic biopsy forceps.

INTRODUCTION: We sought to assess the adequacy of surgical specimens obtained utilizing the BIGopsy (Cook Medical, Bloomington, IN, USA) biopsy forceps both ex vivo and in vivo and compare them to traditional 3Fr biopsy forceps in patients with suspected upper tract urothelial carcinoma. MATERIALS AND METHODS: Patients undergoing nephroureterectomy for suspected upper tract transitional cell carcinoma were recruited. Surgical specimens, immediately after extirpation were examined and alternatively biopsied ex vivo with the BIGopsy and 3Fr biopsy forceps. We then retrospectively reviewed our most recent experience with ureteroscopic biopsy. The biopsy device, size, depth, grade, stage, pathologic diagnosis and subjective biopsy quality were assessed. RESULTS: Three ex vivo nephroureterectomy specimens were evaluated. The average biopsy size from the 3Fr biopsy forceps was 3.5 +/- 2.8 mm2 and for the BIGopsy was 31.2 +/- 34.6 mm2. Subjectively, the BIGopsy specimens revealed less distortion and fragmentation and were easier to interpret by the pathologist. Sixteen patients underwent 19 ureteroscopic procedures. The mean size in maximal diameter (mm +/- SD) of the biopsies in each group were; 3Fr 1.2 +/- 0.4, BIGopsy 3.4 +/- 2.0, nitinol basket 4.9 +/- 4.0 and laser 11 +/- 8.5. Lamina propria was identified in 3/13 (23%) biopsies with 3Fr biopsy forceps, 6/11 (55%) biopsies with the BIGopsy forceps, 6/8 (75%) biopsies with the nitinol basket and 2/2 (100%) biopsies with the holmium laser. Six patients underwent biopsies with both the BIGopsy and 3Fr biopsy forceps. A definitive diagnosis was made in 2/6 cases with the 3Fr biopsy forceps compared with all 6/6 cases with the BIGopsy biopsy forceps. Grade and stage matched final surgical grade and stage in 3/3 cases biopsied with the BIGopsy. CONCLUSION: For lesions with stalks, the holmium laser and basket biopsy provided larger specimens than either of the forceps. For flat or sessile lesions, the BIGopsy biopsy forceps provided larger, deeper less distorted specimens than the 3Fr biopsy forceps and correlated well with ultimate grade and stage. Improved biopsy quality may translate into improved ability to diagnose both benign and malignant ureteral and renal pelvic mucosal lesions endoscopically.