Autophagy and urothelial carcinoma of the bladder: A review.

The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer

Male LUTS – Introduction and Overview

Outline & Goals • Background – What are “LUTS”? • Anatomy • Pathophysiology Storage – bladder filling symptoms Voiding – urine flow symptoms Post-micturition • Major etiologies and management BPH / BOO OAB Nocturia • Related to Prostate Cancer

Zero Tolerance – Mitigating the Opioid Epidemic Amongst Minimally Invasive Urologic Patients

Introduction: Opioids are routinely prescribed following minimally invasive surgery (MIS), yet the majority of medication remains unused. However, the literature is lacking evidence for non-narcotic analgesia in MIS urologic procedures. The purpose of this study is to evaluate the efficacy of a non-narcotic postoperative pain management regimen in reducing opioid use following MIS urologic procedures. Methods: In this prospective study, 51 MIS urologic patients were recruited over two months. Patients in the first month cohort (P1) were managed with the established pain management standard-of-care, while patients in the second month (P2) followed a non-narcotic postoperative pain management protocol that included an “opt-in” requirement for opioids. Protocol efficacy was assessed using self-reported patient pain scores at three time points, total postoperative hospital opioid utilization, and the need for opioids at discharge. Data analysis included descriptive statistics and student’s t-test. Results: Total mean values revealed 27.9% reduction in morphine equivalent dose (MED) prescribed, 19.7% reduction in MED used by patients, and 70% reduction in number of patients prescribed any opioids at time of discharge in P2 patients compared to P1 patients (p-value \u3c0.001). There was no significant difference between P1 and P2 in patient pain scores at each time point. Discussion: Overall, the new non-narcotic pain management protocol reduced postoperative opioid utilization in patients undergoing urologic MIS without compromising pain control. This study demonstrates that instituting a single “opt-in” postoperative pain management protocol with appropriate patient education helped significantly reduce the use of postoperative opioids

Stress Urinary Incontinence post-Holmium Laser Enucleation of the Prostate: a Single-Surgeon Experience.

PURPOSE: To identify incidence and predictors of stress urinary incontinence (SUI) following Holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: We performed a retrospective review of 589 HoLEP patients from 2012-2018. Patients were assessed at pre-operative and post-operative visits. Univariate and multivariate regression analyses were performed to identify predictors of SUI. RESULTS: 52/589 patients (8.8%) developed transient SUI, while 9/589 (1.5%) developed long-term SUI. tSUI resolved for 46 patients (88.5%) within the first six weeks and in 6 patients (11.5%) between 6 weeks to 3 months. Long-term SUI patients required intervention, achieving continence at 16.4 months on average, 44 men (70.9%) with incontinence were catheter dependent preoperatively. Mean prostatic volume was 148.7mL in tSUI patients, 111.6mL in long-term SUI, and 87.9mL in others (p \u3c 0.0001). On univariate analysis, laser energy used (p \u3c 0.0001), laser on time (p=0.0204), resected prostate weight (p \u3c 0.0001), overall International Prostate Symptom Score (IPSS) (p=0.0005), and IPSS QOL (p=0.02) were associated with SUI. On multivariate analysis, resected prostate weight was predictive of any SUI and tSUI, with no risk factors identified for long-term SUI. CONCLUSION: Post-HoLEP SUI occurs in ~10% of patients, with 1.5% continuing beyond six months. Most patients with tSUI recover within the first six weeks. Prostate size \u3e100g and catheter dependency are associated with increased risk tSUI. Larger prostate volume is an independent predictor of any SUI, and tSUI

Identification of an oxygenic reaction center psbadc operon in the cyanobacterium gloeobacter violaceus PCC 7421

Gloeobacter violaceus, the earliest diverging oxyphotobacterium (cyanobacterium) on the 16S ribosomal RNA tree, has five copies of the photosystem II psbA gene encoding the D1 reaction center protein subunit. These copies are widely distributed throughout the 4.6 Mbp genome with only one copy colocalizing with other PSII subunits, in marked contrast to all other psbA genes in all publicly available sequenced genomes. A clustering of two other psb genes around psbA3 (glr2322) is unique to Gloeobacter. We provide experimental proof for the transcription of a psbA3DC operon, encoding three of the five reaction center core subunits (D1, D2, and CP43). This is the first example of a transcribed gene cluster containing the D1/D2 or D1/D2/CP43 subunits of PSII in an oxygenic phototroph (prokaryotic or eukaryotic). Implications for the evolution of oxygenic photosynthesis are discussed. © The Author 2011

Non-obstetrical robotic-assisted laparoscopic surgery in pregnancy: a systematic literature review.

Urologic and gynecologic surgeons are the top utilizers of robotic surgery; however, non-obstetrical robotic-assisted laparoscopic surgery (RALS) in pregnant patients is infrequent. A systematic literature review was performed to ascertain the frequency, indication and complications of RALS in pregnancy. Results showed thirty-eight pregnancies from eleven publications between 2008-2020. Five cases were for urologic indication and thirty-three for gynecologic indication. Minimal surgical alterations were required. Although no adverse maternal-fetal outcomes were reported, there are not enough cases published to determine safety. This review demonstrates the feasibility of RALS for the pregnant population in the hands of competent robotic surgeons

Collaborative Review: Factors Influencing Treatment Decisions for Patients with a Localized Solid Renal Mass.

CONTEXT: With the addition of active surveillance and thermal ablation (TA) to the urologist\u27s established repertoire of partial (PN) and radical nephrectomy (RN) as first-line management options for localized renal cell carcinoma (RCC), appropriate treatment decision-making has become increasingly nuanced. OBJECTIVE: To critically review the treatment options for localized, nonrecurrent RCC; to highlight the patient, renal function, tumor, and provider factors that influence treatment decisions; and to provide a framework to conceptualize that decision-making process. EVIDENCE ACQUISITION: A collaborative critical review of the medical literature was conducted. EVIDENCE SYNTHESIS: We identify three key decision points when managing localized RCC: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality (TA, PN, or RN), and (3) decision on surgical approach (open vs minimally invasive). In evaluating factors that influence these treatment decisions, we elaborate on patient, renal function, tumor, and provider factors that either directly or indirectly impact each decision point. As current nomograms, based on preselected patient datasets, perform poorly in prospective settings, these tools should be used with caution. Patient decision aids are an underutilized tool in decision-making. CONCLUSIONS: Localized RCC requires highly nuanced treatment decision-making, balancing patient- and tumor-specific clinical variables against indirect structural influences to provide optimal patient care. PATIENT SUMMARY: With expanding treatment options for localized kidney cancer, treatment decision is highly nuanced and requires shared decision-making. Patient decision aids may be helpful in the treatment discussion

Patient Factors Impacting Perioperative Outcomes for T1b-T2 Localized Renal Cell Carcinoma May Guide Decision for Partial versus Radical Nephrectomy

There remains debate surrounding partial (PN) versus radical nephrectomy (RN) for T1b-T2 renal cell carcinoma (RCC). PN offers nephron-sparing benefits but involves increased perioperative complications. RN putatively maximizes oncologic benefit with complex tumors. We analyzed newly available nephrectomy-specific NSQIP data to elucidate predictors of perioperative outcomes in localized T1b-T2 RCC. We identified 2094 patients undergoing nephrectomy between 2019-2020. Captured variables include surgical procedure and approach, staging, comorbidities, prophylaxis, peri-operative complications, reoperations, and readmissions. 816 patients received PN while 1278 received RN. Reoperation rates were comparable; however, PN patients more commonly experienced 30-day readmissions (7.0% vs. 4.7%, p = 0.026), bleeds (9.19% vs. 5.56%, p = 0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p = 0.013) and urine leak or fistulae (1.10% vs. 0.31%, p = 0.025). Infectious, pulmonary, cardiac, and venothromboembolic event rates were comparable. Robotic surgery reduced occurrence of various complications, readmissions, and reoperations. PN remained predictive of all four complications upon multivariable adjustment. Several comorbidities were predictive of complications including bleeds and readmissions. This population-based cohort explicates perioperative outcomes following nephrectomy for pT1b-T2 RCC. Significant associations between PN, patient-specific factors, and complications were identified. Risk stratification may inform management to improve post-operative quality of life (QOL) and RCC outcomes

Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men.

BACKGROUND: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing. OBJECTIVE: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands. DESIGN, SETTING, AND PARTICIPANTS: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher\u27s exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx. RESULTS AND LIMITATIONS: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes. CONCLUSIONS: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies. PATIENT SUMMARY: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families

Robotic Adrenalectomy for Functional Adenoma in Second Trimester Treats Worsening Hypertension.

A 33-year-old G6P3023 was found to have a 4.2 cm right adrenal incidentaloma during an admission for right pyelonephritis. Computed tomography (CT) was performed to rule out perinephric abscess in the setting of worsening leukocytosis while on antibiotics ( Fig. 1). Initial differential diagnosis from endocrinology included pheochromocytoma and primary aldosteronism. Due to the lack of typical physical exam stigmata, Cushing syndrome was initially of low concern. Of note, her past medical history included hypertension treated with amlodipine 10 mg and hydrochlorothiazide 12.5 mg. During admission, extensive endocrine laboratory workup demonstrated an elevated aldosterone:plasma renin activity, suppressed dehydroepiandrosterone (DHEA), normal 24-hour urine metanephrine and catecholamine, and hypokalemia ( Table 1). This initial biochemical workup did not provide any definitive diagnosis; however, it did convincingly rule out pheochromocytoma due to the normal catecholamine levels in the serum and urine. Eliminating this pathology was critical due to the mortality of hypertensive crisis in the perioperative period