miR-218 Expressed in Endothelial Progenitor Cells Contributes to the Development and Repair of the Kidney Microvasculature.

Ischemia due to hypoperfusion is one of the most common forms of acute kidney injury. We hypothesized that kidney hypoxia initiates the up-regulation of miR-218 expression in endothelial progenitor cells (EPCs) to guide endocapillary repair. Murine renal artery-derived EPCs (CD34+/CD105-) showed down-regulation of mmu-Mir218-5p/U6 RNA ratio after ischemic injury, while in human renal arteries, MIR218-5p expression was up-regulated after ischemic injury. MIR218 expression was clarified in cell culture experiments in which increases in both SLIT3 and MIR218-2-5p expressions were observed after 5 minutes of hypoxia. ROBO1 transcript, a downstream target of MIR218-2-5p, showed inverse expression to MIR218-2-5p. EPCs transfected with a MIR218-5p inhibitor in three-dimensional normoxic culture showed premature capillary formation. Organized progenitor cell movement was reconstituted when cells were co-transfected with Dicer siRNA and low-dose Mir218-5p mimic. A Mir218-2 knockout was generated to assess the significance of miR-218-2 in a mammalian model. Mir218-2-5p expression was decreased in Mir218-2-/- embryos at E16.5. Mir218-2-/- decreased CD34+ angioblasts in the ureteric bud at E16.5 and were nonviable. Mir218-2+/- decreased peritubular capillary density at postnatal day 14 and increased serum creatinine after ischemia in adult mice. Systemic injection of miR-218-5p decreased serum creatinine after injury. These experiments demonstrate that miR-218 expression can be triggered by hypoxia and modulates EPC migration in the kidney.

Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks.

Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. We investigated the function of renal artery progenitor cells derived from radical nephrectomy patients, in animal models of acute ischemic and hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative cells were clonal and expressed transcription factors Sox2/Oct4 as well as surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected cells were associated with decreased serum creatinine after ischemia/reperfusion, reduced albuminuria after hyperperfusion, and improved blood flow in both models. A small population of RAPC integrated with the renal microvasculature following either experimental injury. At a cellular level, RAPC promoted local endothelial migration in co-culture. Profiling of RAPC microRNA identified high levels of miRNA 218; also found at high levels in exosomes isolated from RAPC conditioned media after cell contact for 24 hours. After hydrogen peroxide-induced endothelial injury, RAPC exosomes harbored Robo-1 transcript; a gene known to be regulated by mir218. Such exosomes enhanced endothelial cell migration in culture in the absence of RAPC. Thus, our work shows the feasibility of pre-emptive pro-angiogenic progenitor cell procurement from a targeted patient population and potential therapeutic use in the form of autologous cell transplantation.

Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

INTRODUCTION: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. RESULTS: Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS. CONCLUSION: ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.

Renal cell carcinoma containing abundant non-calcified fat.

Renal masses found to contain macroscopic fatty elements on CT or MRI imaging can generally be classified as benign angiomyolipomas. Rarely, renal cell carcinomas may also contain evidence of macroscopic fat. When true adipocytic elements are present, this is generally due to a process of osseous metaplasia in which both fat cells and calcification are co-localized within the mass. We present a patient with a large papillary renal cell carcinoma containing abundant fat with sparse, punctate calcification remote from the fatty elements on imaging. This report highlights the need for radiologists to maintain caution when diagnosing renal angiomyolipomas on the basis of macroscopic fat and reviews the current literature on fat-containing renal masses.

Evidence-Based Analysis of the Critical Steps of Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is an integral part of the management of patients with advanced-stage bladder cancer. This major oncologic operation is prone to complications resulting in morbidity and mortality. We analyzed the critical steps of open RC, performed an evidence-based review of these steps, and discussed our experience and approach. We conducted a literature review of the open RC technique, identified the critical steps that consistently appeared across different sources, and organized these steps into a framework. PubMed was queried with the critical steps as keywords for relevant articles published from 1 January 2013 to 1 August 2023. We utilized this query to conduct a systematic review of the literature using the outcomes of overall survival and 90-day complication rate. We developed the "Summary for the 10 Critical Operative Steps of Radical Cystectomy", a concise guide to the approach to open RC. When available, an evidence-based analysis of each critical step was performed. We also included additional components of cystectomy optimization such as pre-habilitation in the preoperative phase, standard versus extended lymphadenectomy, the vaginal-sparing approach to female radical cystectomy, patient-reported outcomes following urinary diversion, the use of a mesh for stoma formation, and the use of the ERAS protocol for postoperative care. An evidence-based assessment of RC may help provide valuable information to optimize surgical techniques and patient outcomes.

Anticoagulation prophylaxis patterns following retroperitoneal lymph node dissection for testis cancer.

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is the standard of care for testicular cancer in various disease settings. Deep vein thrombosis (DVT) complications have been reported to occur in <1% of primary RPLND cases and up to 3% of postchemotherapy (PC-RPLND) cases. While prophylactic anticoagulation (AC) has been well-documented to reduce DVT rates in patients undergoing surgery in general, the benefit of prophylactic AC in RPLND has not been assessed. In this retrospective cohort study, we seek to address this unmet need by evaluating the rates and associated risk factors of DVT and pulmonary embolism (PE) with a national and institutional database, assess the changing patterns in DVT prophylaxis with postoperative AC following RPLND, and quantify the potential benefit of prophylactic AC in patients who have undergone RPLND using a risk-stratified approach. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent RPLND during the 10-year period from 2011 to 2021. An institutional database was queried for all patients undergoing RPLND from 2013 to 2022. Patient characteristics and operative outcomes were compared between the NSQIP and the institutional database. The institutional database was stratified by prior oncologic treatment (i.e., primary RPLND vs. PC-RPLND) and outcomes were compared. Postoperative AC rate was determined and trended by year. The use of postoperative AC and PE events were stratified by clinical stage. The absolute risk reduction (ARR) of AC prophylaxis on PE events and the number needed to treat (NNT) with AC prophylaxis to prevent a single PE event was determined. RESULTS: In total, the NSQIP database query resulted in 779 patients and our institutional database query resulted in 188 patients. The rate of DVT and PE was 1.2% and 0.5% vs. 2.1% and 1.6% in the NSQIP and institutional cohort, respectively. The rate of postoperative AC following RPLND in patients from the institutional database increased from 5% in 2013 to 43% in 2022 (P = 0.01). There were no statistically significant differences in complication rates, including bleeding events, chyle leaks, or hospital readmissions amongst patients who were prescribed AC at discharge and those who were not. No stage I patients developed PEs and no stage I patients were prescribed AC. The ARR for AC prophylaxis for development of PE was found to be 0.023 for the clinical stage II and stage III cohorts. The NNT to prevent a single PE with AC was 44 and 43 for the stage II and stage III cohorts, respectively. CONCLUSIONS: AC appears beneficial with minimal risk of harm after RPLND, especially in patients with higher risk of developing DVT/PE, highlighting the safety and efficacy of this regimen. There was a significant increase in the rate of AC prophylaxis at discharge amongst patients undergoing RPLND in the institutional database from 2013 to 2022. A risk-stratified protocol of postoperative AC following RPLND appears reasonable, and further prospective trials are warranted to formally confirm this recommendation.

Impact of exercise on physical health status in bladder cancer patients.

INTRODUCTION: There is a scarcity of data on the impact of behavioral habits, such as exercise, on physical health in patients with bladder cancer. We investigated the association of exercise on self-reported physical health status and examined the prevalence of bladder cancer patients with sedentary lifestyle. METHODS: We examined cross-sectional data of participants diagnosed with bladder cancer within the Behavioral Risk Factor Surveillance System (BRFSS) from 2016-2020. Patient health status was surveyed using self-reported measures, such as the total days per month when their "physical health is not good." The primary outcome was patient-reported poor physical health for more than 14 days within a one-month period. RESULTS: Out of 2 193 981 survey participants, we identified 936 with a history of bladder cancer. Nearly one in three bladder cancer patients reported being sedentary within the last month, as a total of 307 (32.8%) patients reported no exercise within the last 30 days. The remaining 628 (67.2%) reported exercising for at least one day within the last month. In multivariable logistic regression model analysis, we found that exercise is protective for self-reported poor physical health status (odds ratio 0.37, 95% confidence interval 0.25-0.56, p<0.001). Patients that exercised were less likely to report bad physical health. CONCLUSIONS: Approximately one in three bladder cancer patients report no exercise within 30 days, suggesting a sedentary lifestyle. Patients that are active are less likely to self-report poor physical health status. Implementation of exercise programs for bladder cancer patients could be promising in improving health status.

Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy.

PURPOSE: Bacillus Calmette-Guerin (BCG) is the standard of care for high-risk nonmuscle invasive bladder cancer (NMIBC), but half of patients develop disease recurrence. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety, efficacy, and differential response of sequential gemcitabine/docetaxel (gem/doce) depending on BCG failure classification. METHODS: Multi-institutional retrospective analysis of patients treated with induction intravesical gem/doce (≥5/6 instillations) for recurrent high-risk NMIBC after BCG therapy from May 2018 to December 2021. Maintenance therapy was provided to those without high-grade (HG) recurrence on surveillance cystoscopy. Kaplan-Meier curves and Cox regression analyses were utilized to assess survival and risk factors for disease recurrence. RESULTS: Our cohort included 102 patients with BCG-unresponsive NMIBC. Median age was 72 years and median follow-up was 18 months. Six-, 12-, and 24-month high-grade recurrence-free survival was 78%, 65%, and 49%, respectively. Twenty patients underwent radical cystectomy (median 15.5 months from induction). Six patients progressed to muscle invasive disease. Fifty-seven percent of patients experienced mild/moderate adverse effects (AE), but only 6.9% experienced a delay in treatment schedule. Most common AE were urinary frequency/urgency (41%) and dysuria (21%). Patients with BCG refractory disease were more likely to develop HG recurrence when compared to patients with BCG relapsing disease (HR 2.14; 95% CI 1.02-4.49). CONCLUSIONS: In patients with recurrence after BCG therapy, sequential intravesical gem/doce is an effective and well-tolerated alternative to early cystectomy. Patients with BCG relapsing disease are more likely to respond to additional intravesical gem/doce. Further investigation with a prospective trial is imperative.

Morbidity of open retroperitoneal lymph node dissection for testicular cancer: contemporary perioperative data.

OBJECTIVE: To review differences between primary retroperitoneal lymph node dissection (P-RPLND) and RPLND after chemotherapy (PC-RPLND) in a contemporary series of patients with testicular cancer, to validate the proposed low morbidity. PATIENTS AND METHODS: Patients who had undergone RPLND at our institution in 2001-2008 were identified and their clinical charts reviewed; in all, 190 were identified and perioperative data obtained. RESULTS: Of the 190 patients who had RPLND, 98 (52%) and 92 (48%) had P- and PC-RPLND, respectively. Histology of the orchidectomy specimen consisted of embryonal carcinoma in 146 (76%) patients, also including lymphovascular invasion in 83 (44%). The mean (range) operative duration was 206 (110-475) min and the mean blood loss was 294 (50-7000) mL. The median hospital stay was 4 days. Mean blood loss, operative duration and hospital stay were significantly less for the P-RPLND than for PC-RPLND groups (P < 0.05). There were 18 (9%) perioperative complications in all. There were no deaths in either group. CONCLUSIONS: The short-term morbidity of open RPLND is acceptable, and open RPLND is safe and effective at select tertiary centres. When compared with historical data, the present contemporary series shows that the operative duration, blood loss and hospital stay have improved, with few complications. These contemporary data should be considered when comparing laparoscopic with open RPLND.

Risk factors and reasons for reoperation after radical cystectomy.

PURPOSE: Reoperation after radical cystectomy (RC) is common but the types of reoperation after RC and associated risk factors have not been fully characterized. Here, we provide a detailed, contemporary account of the factors that drive surgical reoperation within the first 30-days after surgery, identify at risk patient populations, and describe common reoperations. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2012-2017) was analyzed to identify 30-day reoperation rates after RC. Captured variables included demographic, preoperative, operative, and postoperative characteristics. Postoperative characteristics included complications, including types of reoperation, length of stay, unplanned readmissions, and discharge destination. Pearson chi-squared and multivariable logistic regression models were used for analysis. RESULTS: A total of 10,848 patients underwent RC and there were 633 (5.84%) unplanned reoperations. On multivariable logistic regression, patient factors associated with increased risk of reoperation included longer operative times at index procedure (>90th percentile operative time) (OR1.41 [1.08-1.83], P = 0.02), smoking (OR1.34 [1.11-1.63], P < 0.01), obesity (BMI≥30) (OR 1.29 [1.04-1.60], P = 0.02) and chronic obstructive pulmonary disease (OR1.74 [1.36-2.3], P < 0.01). Other significant factors included clinically significant hypertension, perioperative blood transfusion, and male sex. The most common reoperation procedures were those performed on the gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by Genitourinary procedures at 8.16% (47). Patients who underwent reoperation were at higher risk for readmission, discharge to a facility, and death (P < 0.01). CONCLUSION: Reoperation after RC is associated with approximately 5% rate of reoperation within 30 days of surgery. The most common reason for reoperation was related to the gastrointestinal tract, accounting for more than 60% of all reoperations. Risk factors for reoperation included longer surgical times, smoking, obesity, chronic obstructive pulmonary disease, perioperative blood transfusion, and clinically significant hypertension. Knowledge of these factors can aid in operative planning and counseling and lead to possible strategies to reduce reoperations in the early perioperative setting.

Implementation of a Perioperative Venous Thromboembolism Prophylaxis Program for Patients Undergoing Radical Cystectomy on an Enhanced Recovery After Surgery Protocol.

BACKGROUND: Novel venous thromboembolism (VTE) prophylaxis programs, including postdischarge pharmacologic prophylaxis, have been associated with decreased VTE rates. Such practices have not been widely adopted in managing radical cystectomy (RC) patients. OBJECTIVE: To evaluate the effect of a perioperative VTE prophylaxis program on VTE rates after RC. DESIGN, SETTING, AND PARTICIPANTS: Single-institution, nonrandomized, pre- and post-intervention analysis of 319 patients undergoing RC at Brigham and Women's Hospital between July 2011 and April 2017. Patient and outcome data were prospectively collected as part of the American College of Surgeons National Surgical Quality Improvement Program. INTERVENTION: Before June 2015, patients only received postoperative pharmacologic and mechanical VTE prophylaxis in the inpatient setting. Starting June 2015, a perioperative VTE prophylaxis program was implemented as part of an enhanced recovery after surgery (ERAS) protocol, including a 28-d course of postdischarge enoxaparin. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was 30-d postoperative VTE rate. Secondary outcomes were perioperative bleeding rates, 30-d complication, readmission, and mortality rates, and length of stay. Univariate analysis was performed comparing outcomes between pre- and post-intervention cohorts. RESULTS AND LIMITATIONS: Of the 319 patients who underwent RC, 210 (66%) were in the pre- and 109 (34%) in the post-intervention cohort. VTE rate was significantly lower in the post-intervention cohort (n=1, 0.9% vs n=13, 6.2%; p=0.04). Rates of perioperative bleeding (35% vs 33%; p=0.80) and 30-d readmissions related to bleeding (1% vs 3.7%; p=0.19) did not differ significantly. Single-institution data limits generalizability, and patient compliance with postdischarge enoxaparin was unknown. CONCLUSIONS: Implementation of a perioperative VTE prophylaxis program as part of an ERAS protocol that includes extended postdischarge pharmacologic prophylaxis was associated with decreased rate of VTE events after RC. Perioperative bleeding and readmissions related to bleeding did not increase with this intervention. PATIENT SUMMARY: This study evaluated whether clotting complication rates after radical cystectomy (RC) for bladder cancer can be reduced by implementing a new postoperative care pathway. This pathway reduced rates of clotting complications without increasing bleeding rates and should be considered for all patients undergoing RC.

Primary retroperitoneal lymph node dissection in patients with clinical stage IS testis cancer.

PURPOSE: Initial management for clinical stage IS (persistently increased tumor markers) nonseminomatous germ cell tumor has evolved from primary retroperitoneal lymph node dissection to induction chemotherapy at most medical centers. We analyzed the outcome in patients treated with primary retroperitoneal lymph node dissection. MATERIALS AND METHODS: We reviewed the charts of patients who underwent retroperitoneal lymph node dissection at Brigham and Women's Hospital, and Dana Farber Cancer Center from 1993 to 2008. All patients with clinical stage IS were identified and perioperative data were obtained. RESULTS: A total of 280 patients who underwent retroperitoneal lymph node dissection were identified, of whom 24 identified with clinical stage IS underwent primary dissection. Median followup was 2.9 years. Histopathology revealed an embryonal carcinoma component in 24 orchiectomy specimens (100%) with associated teratoma in 15 (63%). Positive lymph nodes were identified at retroperitoneal lymph node dissection in 9 patients (38%), including pure embryonal carcinoma in 6 (67%), combined embryonal carcinoma and teratoma in 1, embryonal carcinoma, choriocarcinoma and teratoma in 1, and only teratoma in 1. Of the patients who underwent primary retroperitoneal lymph node dissection 5 (21%) also received chemotherapy postoperatively, which was due to persistently increased tumor markers in 3 (13%). No retroperitoneal recurrence was noted on followup imaging. At surgery estimated blood loss was 175 cc, operative time was 3.1 hours and hospital stay was 3.9 days. There were no deaths. CONCLUSIONS: Patients with clinical stage IS are at significant risk for metastatic disease and can be successfully treated with primary retroperitoneal lymph node dissection, thereby sparing chemotherapy in most of them. Retroperitoneal recurrence is essentially eliminated when retroperitoneal lymph node dissection is performed in this select patient group.

Retroperitoneal lymph node dissection in patients with high risk testicular cancer.

PURPOSE: In patients with testicular cancer the percent of embryonal carcinoma and lymphovascular invasion in the primary tumor have been identified as risk factors for occult metastatic disease. We reviewed differences between primary and post-chemotherapy retroperitoneal lymph node dissection in patients at high risk. MATERIALS AND METHODS: Patients who underwent retroperitoneal lymph node dissection at our institution from 1993 to 2006 were identified and the clinical charts were reviewed. A total of 247 patients with orchiectomy specimens containing greater than 30% embryonal carcinoma were identified and perioperative data were obtained. RESULTS: Of 247 patients 133 (53%) had greater than 30% embryonal carcinoma, including 76 (57%) with combined lymphovascular invasion. Median followup was 3.49 years. Of the patients 76 (57%) and 57 (43%) underwent primary and post-chemotherapy retroperitoneal lymph node dissection, respectively, of whom most received bleomycin, etoposide and cisplatin. Positive lymph nodes were identified at surgery in 37 (49%) and 35 patients (61%) with primary and post-chemotherapy retroperitoneal lymph node dissection, respectively. Of patients with negative pathological findings at surgery surveillance computerized tomography postoperatively identified retroperitoneal masses in 2 (5%) and 3 (14%) of those who underwent a primary and a post-chemotherapy procedure, respectively. Operative data on the primary vs post-chemotherapy groups showed an estimated blood loss of 166 vs 371 cc, an operative time of 2.7 vs 3.3 hours and a hospital stay of 4.4 vs 4.7 days. There were no deaths in either group. CONCLUSIONS: Patients with greater than 30% embryonal carcinoma with or without lymphovascular invasion are at significant risk for metastatic disease and they can be successfully treated with primary retroperitoneal lymph node dissection. Recurrence rates based on computerized tomography evaluation were low and similar between the chemotherapy and nonchemotherapy treated groups.

Clear cell tubopapillary renal cell carcinoma mimicking polycystic kidney disease: A case report.

Clear cell tubopapillary renal cell carcinoma (CCTP-RCC) is a distinct histologic subtype of RCC recognized for its unique clinicopathologic and immunohistochemical features. A 72-year-old man with presumed polycystic kidney disease (PKD) and bilateral clear cell RCC (CC-RCC) underwent left radical nephrectomy and right partial nephrectomy 20 years ago at an outside hospital. On surveillance imaging, RCC recurrence was suspected and right radical nephrectomy was performed. Histologic and gross examination of the right remaining kidney was consistent with CCTP-RCC. Review of his original pathology report revealed both kidneys in fact represented CCTP-RCC, mimicking PKD.

Enrichment of FGFR3-TACC3 Fusions in Patients With Bladder Cancer Who Are Young, Asian, or Have Never Smoked.

PURPOSE: FGFR3-TACC3 (fibroblast growth factor receptor 3-transforming acidic coiled coil-containing protein 3) fusions have recently been identified as driver mutations that lead to the activation of FGFR3 in bladder cancer and other tumor types and are associated with sensitivity to tyrosine kinase inhibitors. We examined the clinical and molecular characteristics of patients with FGFR3-TACC3 fusions and hypothesized that they are enriched in a subset of patients with bladder cancer. MATERIALS AND METHODS: We correlated somatic FGFR3-TACC3 fusions with clinical and molecular features in two cohorts of patients with bladder cancer. The first cohort consisted of the muscle-invasive bladder cancer (MIBC) data set (n = 412) from The Cancer Genome Atlas. The second cohort consisted of patients with MIBC or high-grade non-MIBC at the Dana-Farber Cancer Institute that had targeted capture sequencing of a selected panel of cancer genes (n = 356). All statistical tests were two sided. The clinical response of one patient with FGFR3-TACC3 bladder cancer to an FGFR3 inhibitor was investigated. RESULTS: Overall, 751 patients with high-grade bladder cancer without FGFR3-TACC3 fusions and 17 with FGFR3-TACC3 fusions were identified in the pooled analysis of the data sets from The Cancer Genome Atlas and the Dana-Farber Cancer Institute. FGFR3-TACC3 fusions were enriched in patients age ≤ 50 years versus age 51 to 65 years versus those older than 65 years (pooled, P = .002), and were observed in four (12%) of 33 patients age ≤ 50 years in the pooled analysis. Similarly, FGFR3-TACC3 fusions were significantly more common in Asians (13%) compared with African Americans (4%) and whites (2%; pooled, P < .001), as well as in never smokers (5.6%) compared with ever smokers (1.1%; pooled, P < .001). One patient with the fusion who was treated with an FGFR3 inhibitor achieved complete remission for 10 months. CONCLUSION: Clinical testing to identify FGFR3 fusions should be prioritized for patients with bladder cancer who are younger, never smokers, and/or Asian.

A Mammary-type Myofibroblastoma of the Prostate: A Case Report.

We report the case of a 51-year-old gentleman presenting with obstructive and irritative urinary symptoms, found to have a large prostate mass on imaging. A radical prostatectomy was performed and pathological diagnosis revealed a 12 cm mammary-type myofibroblastoma replacing the entire prostate. Mammary-type myofibroblastoma is a rare lesion outside of the breast, and is considered benign. This is the first reported case of a mammary-type myofibroblastoma occurring in the prostate.

Treatment patterns and associated symptom improvement during six months of care for overactive bladder: a prospective, observational study.

BACKGROUND: Several pharmacologic and nonpharmacologic interventions are available for the treatment of symptoms of overactive bladder (OAB). The relationship between type of initial intervention and subsequent symptom improvement and resource utilization has not been explored in detail. OBJECTIVE: The purpose of this study was to assess (1) the proportion of patients continuing with their initially prescribed treatment for OAB 3 and 6 months after the initial evaluation and (2) the relationship between actual treatment patterns, symptom improvement. and number of physician office visits. METHODS: A total of 31 physicians enrolled patients with OAB for this 6-month prospective, observational study. Baseline data on OAB symptom severity and OAB management strategies were obtained and initial treatment(s) were prescribed by physicians during a routine office visit. Follow-up data on symptom changes, treatment changes, number of physician office visits, and the frequency of absorbent pad use were collected via telephone interviews with patients 3 and 6 months after the initial visit. Stepwise logistic regression was used to assess the relationship between patient characteristics, prescription of medication, and symptom improvement. RESULTS: A total of 213 patients were enrolled; 122 (57.3%) and 100 (46.9%) patients provided follow-up data at the 3-month and 6-month assessments, respectively. The mean age was 61.2 years; 85.2% of patients were female, and 77.7% were white. OAB symptom improvement was significantly related to being prescribed medication (odds ratio [OR], 4.3; 95% CI, 1.8-9.9) and the mean number of daily leakage incidents at baseline (OR, 3.2; 95% CI, 1.2-8.4). Although patients who were prescribed drugs at baseline tended to have fewer physician office visits and were less likely to be prescribed nondrug interventions than patients who were not treated initially with drugs, these differences were not statistically significant. CONCLUSIONS: Pharmacologic treatment for symptoms of OAB appears to be associated with greater symptom improvement than nonpharmacologic treatment. Larger studies of experimental design are needed to determine whether patients treated with medication use fewer nondrug interventions and require fewer physician office visits than patients treated without medication.

Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates.

PURPOSE: In advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscle-invasive urothelial cancer (MIUC). PATIENTS AND METHODS: Patients with cT2-cT4, N0-1, M0 MIUC were enrolled. Four cycles of ddMVAC were administered, followed by radical cystectomy. The primary end point was pathologic response (PaR) defined by pathologic downstaging to ≤ pT1N0M0. The study used Simon's optimal two-stage design to evaluate null and alternative hypotheses of PaR rate of 35% versus 55%. Secondary end points included toxicity, disease-free survival (DFS), radiologic response (RaR), and biomarker correlates, including ERCC1. RESULTS: Between December 2008 and April 2012, 39 patients (cT2N0, 33%; cT3N0, 18%; cT4N0, 3%; cT2-4N1, 43%; unspecified, 3%) were enrolled. Median follow-up was 2 years. Overall, 49% (80% CI, 38 to 61) achieved PaR of ≤ pT1N0M0, and we concluded this regimen was effective. High-grade (grade ≥ 3) toxicities were observed in 10% of patients, with no neutropenic fevers or treatment-related death. One-year DFS was 89% versus 67% for patients who achieved PaR compared with those who did not (hazard ratio [HR], 2.6; 95% CI, 0.8 to 8.1; P = .08) and 86% versus 62% for patients who achieved RaR compared with those who did not (HR, 4.1; 95% CI, 1.3 to 12.5; P = .009). We found no association between serum tumor markers or ERCC1 expression with response or survival. CONCLUSION: In patients with MIUC, neoadjuvant ddMVAC was well tolerated and resulted in significant pathologic and radiologic downstaging.

Placement of empty catheters for an HDR-emulating LDR prostate brachytherapy technique: comparison to standard intraoperative planning.

PURPOSE: We sought to determine whether placing empty catheters within the prostate and then inverse planning iodine-125 seed locations within those catheters (High Dose Rate-Emulating Low Dose Rate Prostate Brachytherapy [HELP] technique) would improve concordance between planned and achieved dosimetry compared with a standard intraoperative technique. METHODS AND MATERIALS: We examined 30 consecutive low dose rate prostate cases performed by standard intraoperative technique of planning followed by needle placement/seed deposition and compared them to 30 consecutive low dose rate prostate cases performed by the HELP technique. The primary endpoint was concordance between planned percentage of the clinical target volume that receives at least 100% of the prescribed dose/dose that covers 90% of the volume of the clinical target volume (V100/D90) and the actual V100/D90 achieved at Postoperative Day 1. RESULTS: The HELP technique had superior concordance between the planned target dosimetry and what was actually achieved at Day 1 and Day 30. Specifically, target D90 at Day 1 was on average 33.7 Gy less than planned for the standard intraoperative technique but was only 10.5 Gy less than planned for the HELP technique (p < 0.001). Day 30 values were 16.6 Gy less vs. 2.2 Gy more than planned, respectively (p = 0.028). Day 1 target V100 was 6.3% less than planned with standard vs. 2.8% less for HELP (p < 0.001). There was no significant difference between the urethral and rectal concordance (all p > 0.05). CONCLUSIONS: Placing empty needles first and optimizing the plan to the known positions of the needles resulted in improved concordance between the planned and the achieved dosimetry to the target, possibly because of elimination of errors in needle placement.