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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Variability in MRI vs. ultrasound measures of prostate volume and its impact on treatment recommendations for favorable-risk prostate cancer patients: a case series.

BACKGROUND: Prostate volume can affect whether patients qualify for brachytherapy (desired size ≥20 mL and ≤60 mL) and/or active surveillance (desired PSA density ≤0.15 for very low risk disease). This study examines variability in prostate volume measurements depending on imaging modality used (ultrasound versus MRI) and volume calculation technique (contouring versus ellipsoid) and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. METHODS: We examined 70 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had volume estimates by three methods: contoured axial ultrasound slices, ultrasound ellipsoid (height × width × length × 0.523) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation. RESULTS: Average gland size by the contoured ultrasound, ellipsoid ultrasound, and erMRI methods were 33.99, 37.16, and 39.62 mLs, respectively. All pairwise comparisons between methods were statistically significant (all p < 0.015). Of the 66 patients who volumetrically qualified for brachytherapy on ellipsoid ultrasound measures, 22 (33.33%) did not qualify on ellipsoid erMRI or contoured ultrasound measures. 38 patients (54.28%) had PSA density ≤0.15 ng/dl as calculated using ellipsoid ultrasound volumes, compared to 34 (48.57%) and 38 patients (54.28%) using contoured ultrasound and ellipsoid erMRI volumes, respectively. CONCLUSIONS: The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 9.34% and 16.57% respectively. 33.33% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI ellipsoid volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results.

BACKGROUND: Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS: A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after attempted placement of 10cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS: Spacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node-positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION: Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.

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.

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.

Blood-based biomarkers of aggressive prostate cancer.

PURPOSE: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. MATERIALS AND METHODS: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. RESULTS: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. CONCLUSION: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

Need for intraoperative ultrasound and surgical recommendation for partial nephrectomy: correlation with tumor imaging features and urologist practice patterns.

PURPOSE: This study aimed to evaluate the need for intraoperative ultrasound (IOUS) and recommendation for surgical approach in the resection of renal tumors through a survey of practicing urologists, with correlation to tumor imaging features and urologist practice pattern. MATERIALS AND METHODS: An institutional review board-approved retrospective review, compliant with the Health Insurance Portability and Accountability Act, of 44 renal tumors that underwent laparoscopic partial nephrectomy at the study institution was performed. The numeric component of the RENAL nephrometry score (radius [diameter], % exophytic, nearness [to collecting system/renal sinus], location) was calculated for each case using preoperative computed tomography/magnetic resonance imaging. Five anonymized images of each tumor were presented to 4 academic urologists with varying practice patterns. Reviewers independently scored each case for its need for IOUS, for recommendation of a surgical technique, and for the difficulty of the proposed surgery. RESULTS: The RENAL scores were as follows: RENAL 1 (low complexity, score 4-6; n = 19); RENAL 2 (moderate complexity, score 7-9; n = 23); RENAL 3 (high complexity, score 10-12; n = 2). The only RENAL score component significantly influencing need for IOUS was percentage exophytic (P = 0.00002). There was an inverse relationship between normalized and averaged need for IOUS and percentage exophytic (P < 0.0001). The predominant influence for recommendation of surgical method was the reviewer him/herself, with each reviewer's recommendations closely matching his/her practice pattern. Size and percentage exophytic represented the only tumor features significantly (P = 0.03) influencing surgical recommendation. CONCLUSIONS: There was a significant difference in the perceived need for IOUS and surgical recommendation when 4 academic urologists reviewed a series of renal masses requiring resection. Percentage exophytic correlated inversely with need for IOUS. Urologist's practice pattern and tumor size and percentage exophytic were most predictive of surgical recommendation.

Primary vs. post-chemotherapy retroperitoneal lymph node dissection (RPLND) in patients with presence of teratoma at orchiectomy.

OBJECTIVE: The presence of teratoma in the primary orchiectomy specimen creates controversies for subsequent management. Although predominant teratoma is less likely to metastasize, teratoma in the retroperitoneum may be less amenable to chemotherapy. In order to elucidate the issues about teratoma in the primary tumor, we reviewed differences between primary retroperitoneal lymph node dissection (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND) in patients with teratoma at orchiectomy. MATERIALS AND METHODS: Patients who had undergone RPLND at our institution from 2001 to 2008 were identified, and clinical charts reviewed. Eighty-three patients with teratoma at orchiectomy were identified and perioperative data were obtained. RESULTS: Of the 83 patients with teratoma at orchiectomy who underwent RPLND, 44 (53%) and 39 (47%) underwent primary and PC-RPLND, respectively. Median follow-up was 1.4 years. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were 19 (43%) positive lymph nodes for P-RPLND, of which 13 (30%) contained teratoma. For the PC-RPLND group, 30 (77%) of lymph nodes were positive, of which 28 (72%) contained teratoma. There were 3 (4%) recurrences overall, all of which recurred in the PC-RPLND group. There were 11 (13%) perioperative complications total. There were no deaths in either group. CONCLUSIONS: Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND.