Single-Dose Post-Office Fulguration Mitomycin C Instillation Appears to Improve Recurrence-Free Survival in Patients With Low-Grade Noninvasive Bladder Cancer.

INTRODUCTION: Perioperative instillation of mitomycin-C (MMC) has shown effectiveness in reducing the recurrence of low-grade non-muscle invasive bladder cancer (NMIBC). Data is lacking about the impact of single-dose MMC following office fulguration of low-grade urothelial carcinoma. We compared the outcomes of small-volume low-grade recurrent NMIBC in patients treated with office-fulguration - with and without an immediate single-dose instillation of MMC. PATIENTS AND METHODS: A retrospective analysis of medical records of patients with recurrent small-volume (≤1 cm) low-grade papillary urothelial cancer who underwent fulguration in a single institution between January 2017 and April 2021 either with or without instillation of post-fulguration MMC (40mg/50 mL). The primary outcome was recurrence-free survival (RFS). RESULTS: Of 108 patients (27% women) who underwent fulguration, 41% received intravesical MMC. The treatment and control groups had similar sex ratio, mean age, mass size, tumor multifocality and or tumor grade. Median RFS was 20 months (95% CI 4-36) in the MMC group and 9 months (95% CI 5-13) in the control group (P = .038). Multivariate Cox regression analysis showed that MMC instillation was associated with longer RFS (OR = 0.552, 95% CI 0.320-0.955, P = .034) and multifocality was associated with shorter RFS (OR = 1.866, 1.078-3.229, P = .026). A higher rate of grade 1-2 adverse events was observed in the MMC group (18.2%) vs. the control (6.8%, P = .048). No complications grade 3 or higher were observed. CONCLUSION: A single dose of MMC instilled after office fulguration is associated with longer RFS compared to patients who did not receive MMC after the procedure, with no associated high-grade complications.

Myopericytoma of the ureter Incidental finding of a benign slowly growing tumor.

We present a unique case of a 6 cm, incidental, ureteral myopericytoma which was initially believed to be an ovarian tumor with mass effect, causing hydroureteronephrosis. A 75-year-old woman presented with a three-month history of postprandial cramps and heartburn. A right distal ureterectomy with en-bloc resection of the mass was performed. Histologically, a well-circumscribed, cellular proliferation of uniform, cytologically bland, spindle cells was identified that had a multilayered, concentric growth pattern around numerous blood vessels. Immunohistochemically, the spindle lesional cells stained strongly and diffusely with antibodies against smooth muscle actin and failed to stain for pancytokeratin and S100 protein.

A unique case of chromophobe renal cell carcinoma seeding after biopsy.

We report a unique case for a 1.5 cm Chromophobe Renal Cell Carcinoma (ChRCC) tumor recurrence on the posterior abdominal wall along the renal tumor biopsy tract. This case presented on follow up at 4.5 years after radical nephrectomy T1bN0M0. Pathology was confirmed to be a chRCC with later excision of the mass. We believe the recurrence in this case is due to tumor seeding after multiple Renal Tumor biopsies (RTB) performed before surgery, as the tumor was located along the RTB tract.

Implications of a Novel Biopsy Downloading System on Prostate Cancer Detection Rate, Surveillance and Focal Therapy - A Prospective Study.

OBJECTIVE: To examine the SmartBx, a novel biopsy downloading system, allowing downloading of biopsy cores with maximal core preservation as prostate biopsy sampling lacks preservation of core configuration & orientation. METHODS: We prospectively collected cores from TRUS biopsy patients. Half were collected using the SmartBx & half using standard downloading. We measured length of the first ∼3200 cores through various pathology steps and within core cancer length in 160 SmartBx cores. We compared core length, yield (% of core available for final analysis/ original core on needle) and cancer detection rate between SmartBx and standard cores. T-test or chi-square were used for analysis. RESULTS: 6014 cores were collected from 429 patients. Core length (12.3mm vs. 10mm; P<.01) and core yield (77.5% vs. 62.2%; P<.01) were significantly higher using the SmartBx compared to standard method, respectively. Cancer detection rate was significantly higher using the SmartBx for patients with PSA<10 (10.1% vs. 7.96%; n=2080 & n=2073, respectively; P<.016). Other subgroups showed non-significant higher detection rate for SmartBx cores. We noticed higher detection rate of clinically significant prostate cancer. Within core cancer length in 160 SmartBx cores was significantly lower compared to standard positive whole cores (4.45mm vs. 10.9mm; P<.001). Assuming cancer site a perfect sphere, disease volume was 11-fold lower for within core compared to entire core (46.1mm vs. 679.9mm; P<.0001). CONCLUSIONS: SmartBx results in significant higher core length, yield and cancer detection rate. Precise localization of within core tumor foci allows significant reduction in tumor volume.

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer.

BACKGROUND: To assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors. PATIENTS AND METHODS: We retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis. RESULTS: Of 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease. CONCLUSION: The absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.

A Randomized Controlled Trial of a Modified Cystoscopy Technique using the Peak-End Rule in order to Improve Pain and Anxiety.

OBJECTIVE: To determine if a modified cystoscopy technique utilizing the peak-end rule cognitive bias decreases pain and anxiety during flexible cystoscopy in patients who undergo cystoscopy. METHODS: A total of 85 participants undergoing their first diagnostic cystoscopy were enrolled in a blinded single-center, prospective, randomized controlled trial. Patients with lower urinary tract abnormalities, prior radiation and chronic pelvic pain were excluded. Participants were randomized to a standard cystoscopy (arm A) or a modified cystoscopy (arm B) where a two-minute period at the end of the procedure was completed during which the cystoscope was left in the bladder without being manipulated. Following the cystoscopy, participants completed a standard pain and anxiety questionnaire. Differences in mean pain and anxiety score between arms were evaluated using a Mann-Whitney test with a two-sided alpha of 0.05. RESULTS: Eighty-five patients were randomized and underwent flexible cystoscopy. Three participants were ineligible, one required secondary procedures, and two did not complete the questionnaires. Among the 82 eligible patients, 45 were randomized to standard cystoscopy (arm A) and 37 to the modified cystoscopy (arm B) with mean pain scores of 23.20 and 11.97, respectively (P = .039). Mean anxiety scores were 2.09 and 0.88 for arm A and B, respectively (P = .013). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain and anxiety for patients undergoing flexible cystoscopy when employing the modified cystoscopy technique versus the standard practice. This free and straightforward method to improve patient comfort and decrease stress during first time flexible cystoscopy should be considered by clinicians.

Prostatic dystrophic calcification following salvage cryotherapy for prostate cancer - an under-reported entity?

BACKGROUND: Salvage cryoablation (SCA) is an accepted treatment for radio-recurrent prostate cancer with well-established oncological and functional outcomes. Based on one of the longest reported prospective follow-ups in the literature (median 12 years) on 187 patients, this study reports what appears to be an under-appreciated finding in eight patients with dystrophic calcifications (DC) of the prostate following SCA, causing severe bladder outlet obstruction. MATERIALS AND METHODS: Between 1995 and 2004, 187 patients underwent SCA, with a median follow-up of 12 years. This database was reviewed for functional and oncological outcomes and DC were evaluated. RESULTS: Functional data was available in 85 patients, amongst whom eight patients were found to develop DC (9.4%) proven when the patients presented with urinary difficulties and attempted transurethral resection was undertaken for bladder outlet obstruction. Mean time for emergence of significant symptoms of bladder outlet obstruction was 8.6 years from SCA (standard deviation (SD) = 6 years). All eightpatients required permanent drainage (seven suprapubic catheters, one nephrostomy). All patients with DC experienced biochemical recurrence (BCR), compared to 57.1% of the patients with no DC (p = 0.01). CONCLUSION: DC following SCA appears to be an under-reported late adverse effect which may only become evident with long follow-up, and should be included in preoperative counselling.

Short-Term Outcomes of Active Surveillance for Low Risk Prostate Cancer among Men with Germline DNA Repair Gene Mutations.

PURPOSE: Men with germline mutations in DNA repair genes have a higher risk of prostate cancer. Active surveillance is the preferred treatment modality for low risk prostate cancer. However, many fear offering this alternative to men with germline mutations. We describe the short-term oncologic outcomes of active surveillance in a population of men with a high genetic predisposition for prostate cancer. MATERIALS AND METHODS: A prospective cohort of men with germline DNA repair gene mutations were diagnosed with Grade Group 1 prostate cancer. All men were offered active surveillance. Followup consisted of prostate specific antigen every 3 months, multiparametric magnetic resonance imaging and a magnetic resonance imaging-ultrasound fusion confirmatory biopsy within 1 year of diagnosis. The primary end points included treatment and progression-free survival. RESULTS: Eighteen carriers of DNA repair gene mutations were diagnosed with low risk prostate cancer (BRCA1 [8], BRCA2 [6], CHEK2 [2], Lynch syndrome [2]). Of these patients 15 (83%) initiated active surveillance and 3 (17%) declined. All but 1 were fully compliant with the active surveillance protocol (93%). Overall 20% (3) had upgrading at confirmatory biopsy and were treated. At a median followup of 28 months (IQR 8.5-42) 80% of patients (12) on active surveillance are free from upgrading or radical treatment. CONCLUSIONS: Active surveillance may be feasible among carriers diagnosed with low risk prostate cancer. If embarking on active surveillance, carriers should be very carefully monitored at a specialized clinic, optimizing patient compliance and minimizing risk. Until larger scale studies with long-term followup become available, this option should be cautiously discussed with the patient.

Screening, Active Surveillance, and Treatment of Localized Prostate Cancer Among Carriers of Germline BRCA Mutations.

Male carriers of BRCA mutations are at higher risk of developing prostate cancer. Many issues are still unanswered and are currently being studied, including differences between BRCA1 and BRCA2, screening and specific protocols, the role of active surveillance, and the choice of definitive treatment.

Characterizing the learning curve of MRI-US fusion prostate biopsies.

BACKGROUND: MRI-US fusion prostate biopsies are becoming a common procedure to diagnose prostate cancer. There is a paucity of information regarding the learning curve for fusion biopsies. We aim to study the amount of experience needed to be both accurate and time-efficient in this procedure. METHODS: We prospectively collected data on all MRI-US fusion biopsies performed from April 2014 to August 2017. We used two parameters to define the learning curve. Process Measurement (efficiency) was measured by time from the beginning of anesthesia to end of procedure. Outcome Measurement (accuracy) was measured by cancer detection rate for PI-RAD 3 lesions. The end of the learning curve was defined graphically and mathematically. We performed a separate analysis for transrectal and transperineal biopsies. RESULTS: We completed 779 fusion biopsies (523 transrectal, 256 transperineal). Patients median age was 66 years (IQR 61-70) and median PSA 6.95 ng/ml (IQR 4.2-10.6). Prostate cancer was diagnosed in 385 (49%). Process Measurement-Procedure time decreased from 45 min in the first transrectal fusion biopsy to 15 min after 109 biopsies and remained stable (p < 0.0001). Time decreased from 55 min in the first transperineal biopsy to 18 min after 124 biopsies (p < 0.0001). Outcome Measurement-In transrectal fusion-biopsies detection rate for PI-RADS 3 lesions increased from 35 to 50% after 104 biopsies. In transperineal fusion-biopsies, detection rate increased from 40 to 55% after 119 cases for PI-RADS 3 lesions. CONCLUSIONS: We measured the learning curve of fusion biopsies graphically and mathematically. We demonstrated that proficiency occurs after 110 transrectal and 125 transperineal fusion-biopsies.

Bile acids in glucose metabolism in health and disease.

Bile acids (BAs) are cholesterol-derived metabolites that facilitate the intestinal absorption and transport of dietary lipids. Recently, BAs also emerged as pivotal signaling molecules controlling glucose, lipid, and energy metabolism by binding to the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5) in multiple organs, leading to regulation of intestinal incretin secretion, hepatic gluconeogenesis, glycogen synthesis, energy expenditure, inflammation, and gut microbiome configuration. Alterations in BA metabolism and signaling are associated with obesity and type 2 diabetes mellitus (T2DM), whereas treatment of T2DM patients with BA sequestrants, or bariatric surgery in morbidly obese patients, results in a significant improvement in glycemic response that is associated with changes in the BA profile and signaling. Herein, we review the roles of BAs in glucose metabolism in health and disease; highlight the limitations, unknowns, and challenges in understanding the impact of BAs on the glycemic response; and discuss how this knowledge may be harnessed to develop innovative therapeutic approaches for the treatment of hyperglycemia and diabetes.

Transplant Kidney Retrograde Ureteral Stent Placement and Exchange: Overcoming the Challenge.

OBJECTIVE: To present a reliable technique for fluoroscopic controlled, large-bore, ureteral stent placement and exchange in transplant kidneys with persistent ureterovesical strictures. MATERIALS AND METHODS: We reviewed the medical charts of all patients who underwent kidney transplant with persistent ureterovesical strictures who underwent ureteral stent placement or exchange at our institution between 2005 and 2015 using the new technique. Clinical characteristics and treatment outcomes of the study cohort were analyzed. RESULTS: Ureteral stent insertion or stent exchange, using this technique, was performed in 32 renal transplant units. Median operating time was 24 minutes (interquartile range, 21-36.75 minutes). The overall success rate of the technique at first attempt was 96.9%. In 1 patient, drainage of the transplanted kidney with a nephrostomy tube was indicated after procedure failure. No other local or systemic complications were encountered, and no stent encrustation was noted in this cohort of patients. Renal function remained stable in all patients during a median follow-up of 59 months (interquartile range, 28-61 months). CONCLUSION: Herein, we present in detail a step-by-step technique for the insertion and exchange of large-bore ureteral stents in transplanted kidneys. The technique was shown to be safe, effective, and highly successful.

Assessment of Needle Tip Deflection During Transrectal Guided Prostate Biopsy: Implications for Targeted Biopsies.

OBJECTIVES: To measure needle tip deflection during transrectal ultrasound (TRUS) prostate biopsy and evaluate predictors for needle tip deflection. MATERIALS AND METHODS: Analysis of 568 prostate biopsies obtained from 51 consecutive patients who underwent a standard 12-core TRUS guided prostate biopsy. TRUS guided prostate biopsies were performed using BK flex500, with a side-fire biplane probe. Each biopsy core image was captured and clinical data were recorded prospectively. The angle between the expected trajectory of the needle and actual needle course was measured using the longitudinal view of the captured image. The distance between expected and actual needle tip was calculated. We measured median and interquartile needle tip deflection rate stratified by side and location (apex, midgland, base). Univariable and multivariable linear regressions analysis were performed. RESULTS: The overall median needle tip deflection was 1.77 mm (IQR 1.35-2.47). Location did not significantly alter needle deflection measurements. On multivariable linear regression analysis, higher prostate volume (B = 0.007 95%, CI 0.004, 0.011; p < 0.001) and the right sided biopsy (B = 0.191 95%, CI 0.047, 0.336; p = 0.010) emerged as predictors of higher needle tip deflection. CONCLUSIONS: To the best of our knowledge this is the first study to measure needle tip deflection during TRUS guided prostate biopsies. We demonstrated that larger prostate size and biopsy side may affect the accuracy of biopsies. These results may have clinical implication to those performing targeted biopsies.