Selecting patients for magnetic resonance imaging cognitive versus ultrasound fusion biopsy of the prostate: A within-patient comparison.

Objectives: To compare overall agreement between magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) and MRI cognitive fusion biopsy (CB) of the prostate and determine which factors affect agreement for prostate cancer (PCa) who underwent both modalities in a prospective within-patient protocol. Patients and Methods: From August 2017 to January 2021, patients with at least one Prostate Imaging Reporting & Data System (PI-RADS) 3 or higher lesion on multiparametric MRI underwent transrectal FB and CB in a prospective within-patient protocol. CB was performed for each region of interest (ROI), followed by FB, followed by standard 12 core biopsy. Patients who were not on active surveillance were analysed. The primary endpoint was agreement for any PCa detection. McNemar's test and kappa statistic were used to analyse agreement. Chi-square test, Fisher's exact test and Wilcoxon rank sum test were used to analyse disagreement across clinical and MRI spatial variables. A multivariable generalized mixed-effect model was used to compare the interaction between select variables and fusion modality. Statistics were performed using SAS and R. Results: Ninety patients and 98 lesions were included in the analysis. There was moderate agreement between FB and CB (k = 0.715). McNemar's test was insignificant (p = 0.285). Anterior location was the only variable associated with a significant variation in agreement, which was 70% for anterior lesions versus 89.7% for non-anterior lesions (p = 0.035). Discordance did not vary significantly across other variables. In a mixed-effect model, the interaction between anterior location and use of FB was insignificant (p = 0.411). Conclusion: In a within-patient protocol of patients not on active surveillance, FB and CB performed similarly for PCa detection and with moderate agreement. Anterior location was associated with significantly higher disagreement, whereas other patient and lesion characteristics were not. Additional studies are needed to determine optimal biopsy technique for sampling anterior ROI.

National patterns of injury and outcomes of gunshot wounds to the penis: A Trauma Quality Programs retrospective cohort analysis.

AIM: Gunshot wounds (GSW) to the penis represent a rare type of traumatic injury in the civilian United States population. Although small, single-center studies have reported results of care for these types of injured patients, no national analyses have examined this group. METHODS: A cohort of patients with GSW to the penis was identified using the 2017 American College of Surgeons Trauma Quality Programs database, a comprehensive national database of 753 accredited trauma centers. RESULTS: Gunshot wounds to the penis occurred in 722 patients, which represents 1.7% of all GSW patients (n = 41,017). Gunshot wounds from altercations with law enforcement or accidental discharge of a firearm were rare; the vast majority (n = 655, 90.7%) occurred as a result of assault, intentional self-harm, attempted suicide, or attempted homicide. Patients with a major concomitant non-genitourinary injury comprised 119 (16.5%) patients of the cohort. Most patients (n = 499, 69.1%) underwent a genitourinary procedure during their trauma admission. Penile salvage was successful in most cases, with only 13 (1.8%) patients requiring completion penectomy. Most patients (87.8%) required admission with a median length of stay of 49.8 h. Most patients were treated at the initial trauma center without requiring transfer to another center, and complications during admission were rare. CONCLUSIONS: This analysis, the first national examination of care of patients with GSW to the penis, reveals overall favorable outcomes. Admission and surgical intervention were required in most patients, but penectomy was rare and length of stay was generally short. These results will guide resource utilization and quality improvement efforts in this patient cohort.

In-Bore Versus Fusion MRI-Targeted Biopsy of PI-RADS Category 4 and 5 Lesions: A Retrospective Comparative Analysis Using Propensity Score Weighting.

BACKGROUND. Few published studies have compared in-bore and fusion MRI-targeted prostate biopsy, and the available studies have had conflicting results. OBJECTIVE. The purpose of this study was to compare the target-specific cancer detection rate of in-bore prostate biopsy with that of fusion MRI-targeted biopsy. METHODS. The records of men who underwent in-bore or fusion MRI-targeted biopsy of PI-RADS category 4 or 5 lesions between August 2013 and September 2019 were retrospectively identified. PI-RADS version 2.1 assessment category, size, and location of each target were established by retrospective review by a single experienced radiologist. Patient history and target biopsy results were obtained by electronic medical record review. Only the first MRI-targeted biopsy of the dominant lesion was included for patients with repeated biopsies or multiple targets. In-bore and fusion biopsy were compared by propensity score weights and multivariable regression to adjust for imbalances in patient and target characteristics between biopsy techniques. The primary endpoint was target-specific prostate cancer detection rate. Secondary endpoints were detection rate after application of propensity score weighting for cancers in International Society of Urological Pathology (ISUP) grade group 2 (GG2) or higher and detection rate with the use of off-target systematic sampling results. RESULTS. The study sample included 286 men (in-bore biopsy, 191; fusion biopsy, 95). Compared with fusion biopsy, in-bore biopsy was associated with significantly greater likelihood of detection of any cancer (odds ratio, 2.28 [95% CI, 1.04-4.98]; p = .04) and nonsignificantly greater likelihood of detection of ISUP GG2 or higher cancer (odds ratio, 1.57 [95% CI, 0.88-2.79]; p = .12) in a target. When off-target sampling was included, in-bore biopsy and combined fusion and systematic biopsy were not different for detection of any cancer (odds ratio, 1.16 [95% CI, 0.54-2.45]; p = .71) or ISUP GG2 and higher cancer (odds ratio, 1.15 [95% CI, 0.66-2.01]; p = .62). CONCLUSION. In this retrospective study in which propensity score weighting was used, in-bore MRI-targeted prostate biopsy had a higher target-specific cancer detection rate than did fusion biopsy. CLINICAL IMPACT. Pending a larger prospective randomized multicenter comparison between in-bore and fusion biopsy, in-bore may be the preferred approach should performing only biopsy of a suspicious target, without concurrent systematic biopsy, be considered clinically appropriate.

Delayed blood transfusion is associated with mortality following radical cystectomy.

Objectives: To examine the temporal association between blood transfusion and 90-day mortality in patients with bladder cancer treated with radical cystectomy.Methods: This represents a retrospective cohort study of patients treated with radical cystectomy within the Premier Hospital network between 2003 and 2015. Patients outcomes were stratified those who received early blood transfusion (day of surgery) vs delayed blood transfusion (postoperative day ≥1) during the index admission. Primary end point was 90-day mortality following surgery.Results: The median age of 12,056 patients identified was 70 years. A total of 7,201 (59.7%) patients received blood transfusion. Within 90 days following surgery, 57 (2.2%), 162 (5.9%) and 123 (6.7%) patients in the early, delayed and both early and delayed transfused patients died respectively. Following multivariate logistic regression to account for patient (age and Charlson Comorbidity Index [CCI]) and hospital (surgeon volume, surgical approach and academic status) factors, delayed blood transfusion was independently associated with 90-day mortality (Odds ratio [OR], 2.64; 95% Confidence Interval [CI], 1.98-3.53; p < 0.001). A sensitivity analysis defining early blood transfusion as <2 days postoperatively, increased 90-day mortality persisted in patients receiving delayed transfusion (OR, 2.20; 95% CI, 1.63-3.00; p < 0.001). Older patients (≥77 years) with the highest CCI (≥2) had a 7% absolute increase in the predicted probability of 90-day mortality if they were transfused late compared to patients transfused early.Conclusion: Patient undergoing cystectomy may benefit from expedited transfusion to prevent subsequent clinical deterioration which may lead to patient mortality. Future work is needed to elucidate the optimal timing of blood transfusion.

Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma.

IMPORTANCE: The appropriate use of adjuvant targeted therapy (TT) for high-risk locoregional renal cell carcinoma (RCC) after nephrectomy is currently unclear due to mixed results from the relevant randomized controlled trials. National-level survival outcomes and practice trends for the use of adjuvant TT in the United States have not been reported. OBJECTIVE: To compare overall survival for patients who did and did not receive adjuvant TT after nephrectomy for high-risk locoregional RCC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study reviewed the National Cancer Database from 2006 to 2015. Patients with nonmetastatic clear cell RCC who underwent nephrectomy with either stage pT3a or greater or pN+ were included. MAIN OUTCOMES AND MEASURES: Adjuvant TT was defined as receipt of TT within 3 months of nephrectomy. The primary end point was overall survival from initial diagnosis to date of death or censored at last follow-up. Baseline characteristics were described, and a multivariable analysis identified associations for receipt of adjuvant TT. Nearest-neighbor propensity matching was performed to create similar groups for comparison. A survival analysis was performed using Kaplan-Meier analysis and log-rank test. RESULTS: The final study population included 41,127 patients. Two thousand seventy-one patients (5.04%) received off-label adjuvant TT. Younger age, white race, private insurance, positive margins, pT4, and pN+ were associated with receipt of adjuvant TT. After nearest-neighbor propensity matching for clinically and statistically relevant covariates, 1,604 patients remained in the matched cohort, with statistically nonsignificant differences between the groups for all baseline characteristics. Median overall survival was 52 months for patients in the Adjuvant TT group versus 79 months for those who did not receive adjuvant TT (P < 0.001). Decreased overall survival for patients receiving adjuvant therapy was also seen in pathologic subgroups with and without lymph node involvement. CONCLUSIONS: The propensity matched survival analysis revealed significantly decreased overall survival in patients who received off-label adjuvant TT for high-risk locoregional RCC.

The estimated prevalence of missed positive lymph nodes based on extent of lymphadenectomy at radical prostatectomy.

PURPOSE: To determine practice patterns for the extent of lymphadenectomy at radical prostatectomy and associations with detection of pN1 prostate cancer, as well as the impact of lymphadenectomy extent on underdetection of pN1 disease and overall survival. MATERIALS AND METHODS: Prostatectomy cases in the NCDB from 2004 to 2013 were included. Lymphadenectomy extent was defined by the number of nodes examined. Logistic regression was used to identify risk factors for the top quartile of lymph node count and pN1 disease. This model was created to estimate the expected prevalence of pN1, and generated observed over expected ratios. A Cox regression model was used to evaluate the effect of lymph node count on overall survival. RESULTS: Lymphadenectomy was performed in 209,789 (60%) of 358,522 surgeries, with pN1 in 6,428 (3.08%). Increasing quartiles for lymph node count was associated with pN1 (3-5 nodes OR 2.11; 6-8 nodes OR 3.12; ≥9 nodes OR 5.91, all P< 0.001). The logistic regression model suggested that 59% of pN1 cases are missed due to low lymph node count. Increased lymph node count was associated with increasing pN1 detection (O/E: 1-2 nodes = 0.18; 3-5 nodes = 0.37; 6-8 nodes = 0.56; ≥9 nodes = 1.01). Cox proportional hazards modeling demonstrated that the top quartile for lymph node count had improved overall survival (HR 0.93, CI 0.87-0.99, P= 0.03). CONCLUSIONS: Increasing lymphadenectomy extent was associated with pN1 disease on multivariate analysis, and logistic regression modeling suggested a substantial proportion of pN1 were missed due to low lymphadenectomy extent across all risk groups.

Impact of Direct MRI-Guided Biopsy of the Prostate on Clinical Management.

OBJECTIVE. The purpose of this study is to investigate the impact of direct MRI-guided biopsy of the prostate on clinical management in practice. MATERIALS AND METHODS. We retrospectively identified 127 patients with unknown (n = 98) or untreated prostate cancer with a Gleason score of 6 (n = 29) who underwent direct MRI-guided biopsy of the prostate at our institution between August 2013 and January 2018, after initial multiparametric endorectal MRI examination revealed one or more Prostate Imaging Reporting and Data System (PI-RADS or PI-RADSv2) category 4 or 5 target lesion. All available medical and imaging records were reviewed to determine pertinent clinical details, biopsy findings, and postbiopsy management. RESULTS. The mean patient age was 68 years (interquartile range, 63-73 years). Findings from MRI-guided biopsy were positive for 93 of 127 patients (73%), with prostate cancer of Gleason score of 7 or higher diagnosed in 84 of these 93 patients (90%). When stratified by clinical scenario, the rate of positive biopsy findings was 66% (57/86) for patients who had negative findings from one or more prior transrectal ultrasound-guided biopsies, 83% (10/12) for biopsy-naive patients, and 90% (26/29) for patients undergoing active surveillance. Overall, 90 of 127 patients (71%) received a new (n = 67) or upgraded (n = 23) diagnosis of prostate cancer, and 57 of these 90 patients (63%) proceeded to receive treatment with prostatectomy, radiation, or androgen deprivation therapy. CONCLUSION. The results of this study suggest that direct MRI-guided biopsy is associated with high rates of significant prostate cancer detection and subsequent definitive treatment across common clinical scenarios and should be considered an important supplementary diagnostic tool in the appropriate setting.

Optimizing the Sequence of Chemotherapy for Upper Tract Urothelial Carcinoma with Clinically Positive Regional Lymph Nodes.

PURPOSE: Upper tract urothelial carcinoma with clinically positive regional lymph nodes is an aggressive disease state with a high propensity for metastasis and death. The current literature is limited regarding national practice patterns and outcomes in this patient population. MATERIALS AND METHODS: We identified 1,658 patients in the NCDB (National Cancer Database) who had cN+M0 upper tract urothelial carcinoma. Patients were stratified into treatment groups. We compared baseline patient and tumor characteristics between the groups, and completed survival analysis using a multivariate Cox regression model. RESULTS: There were 1,658 patients in the final study population. Preoperative chemotherapy was the least performed treatment. That group comprised 6.8% of the overall population and was associated with the highest median overall survival of 36 months compared to 21 months for adjuvant chemotherapy, 14 for chemotherapy only, 10 for surgery without perioperative chemotherapy and 5 for no treatment. On multivariate analysis preoperative chemotherapy was associated with improved median overall survival compared to that in the adjuvant chemotherapy group (HR 0.58, 95% CI 0.38-0.87). There was no statistically significant difference in survival between the chemotherapy only and the surgery only groups. Of patients in the preoperative chemotherapy group 34.6% achieved pN0 status compared to 10.3% of those who underwent surgery as initial therapy. CONCLUSIONS: Preoperative chemotherapy was the least performed treatment strategy in the management of cN+M0 upper tract urothelial carcinoma but it was associated with the highest median overall survival. There was no difference in survival between the chemotherapy only and the surgery only groups. Overall these results suggest that initial chemotherapy is appropriate in this population when feasible.

Dominant intraprostatic cancer confirmed by direct MRI-guided biopsy: Concordance with histopathological findings.

PURPOSE: To investigate the concordance between dominant intraprostatic cancer seen on endorectal multiparametric MRI and confirmed by MRI-targeted biopsy with histopathological findings at radical prostatectomy, since existing literature has emphasized the miss rather than the concordance rate of MRI. MATERIALS AND METHODS: We retrospectively identified 20 patients who underwent radical prostatectomy after a dominant intraprostatic cancer focus was identified at endorectal multiparametric MRI and confirmed by MRI-targeted biopsy. Concordance was determined by comparing the location and Gleason grade group of dominant tumor at MRI with the location and Gleason grade group determined at histopathological review. RESULTS: Mean patient age was 65 years (range, 48 to 76) and median serum prostatic specific antigen level was 9.4 ng/mL (range, 4.6 to 58.0). In all 20 patients, the location of dominant tumor based on MRI and targeted biopsy corresponded with the dominant tumor location at histopathology. In 9 patients, Gleason grade group was the same at targeted biopsy and final histopathology. In 9 patients, final Gleason grade group was higher and in two patients it was lower. CONCLUSION: Our preliminary results suggest dominant tumor as determined by endorectal multiparametric MRI and confirmed by a positive MRI-targeted biopsy has high concordance with histopathological findings at radical prostatectomy for location, and reasonable concordance for Gleason grade group.

Unconventional Bladder Preservation: Factors Predicting Failure to Receive Definitive Surgery following Chemotherapy for Nonmetastatic Muscle Invasive Bladder Cancer in the National Cancer Database.

PURPOSE: Neoadjuvant chemotherapy is an important adjunct to cystectomy for managing muscle invasive bladder cancer. Using the National Cancer Database we investigated factors that predict failure to undergo surgery following multi-agent chemotherapy for nonmetastatic muscle invasive bladder cancer. MATERIALS AND METHODS: We performed a cohort study in patients diagnosed with cT2-4aN0M0 urothelial cell carcinoma of the bladder between 2004 and 2013 who underwent multi-agent chemotherapy. We excluded those with surgery prior to chemotherapy, clinical T4b disease and those who received radiotherapy. Socioeconomic and clinical predictors, including time from diagnosis to treatment, were analyzed using logistic regression for the receipt of surgery after chemotherapy. Cox proportional hazards modeling was applied to perform time dependent analysis. RESULTS: Of the 4,640 patients who met our study inclusion and exclusion criteria 4,244 (91%) proceeded to surgery. Negative predictors of surgery included African American or Hispanic race (OR 0.58, p = 0.007 and 0.48, p = 0.002, respectively), increasing age (OR 0.44, p <0.001) and greater time between diagnosis and chemotherapy initiation (fourth quartile greater than 59 days, OR 0.51, p <0.001). African American race (HR 0.79, p <0.001), Medicare (HR 0.86, p <0.001) and other government insurance (HR 0.73, p <0.001) were associated with delayed chemotherapy. CONCLUSIONS: Increasing age, African American or Hispanic race and longer time to chemotherapy predicted failure to undergo surgery. Furthermore, African American race was associated with delayed chemotherapy. Chemotherapy was also delayed in patients on Medicare or other government insurance. Longer time to neoadjuvant chemotherapy is a modifiable risk factor that should be closely observed in multimodal cancer treatment.

Retroperitoneal Leydig cell tumor recurrence presenting 14 years after orchiectomy.

Malignant Leydig cell tumor is a rare entity that has been previously described as rapidly progressive and uniformly fatal. We present the case of a malignant Leydig cell tumor that presented 14 years after orchiectomy with an isolated retroperitoneal metastasis. Our patient underwent a retroperitoneal lymph node dissection and has been free of recurrence or progression at 12 months of follow up. Additionally, we describe the symptomatic hormone dysfunction experienced by our patient as a result of his tumor.

Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade.

There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation. Consistent with this, we observed significantly increased lipid droplets, with subsequent mobilization to mitochondria. These changes were abrogated in cells deficient for the essential autophagy gene ATG5 Accordingly, inhibition of PLA2 significantly decreased lipid droplets, decreased oxidative phosphorylation, and increased apoptosis. Together, these results describe how treatment-induced autophagy provides nutrients for cancer cell survival and identifies novel cotreatment strategies to override this survival advantage.

Prostate MRI prior to radical prostatectomy: effects on nerve sparing and pathological margin status.

OBJECTIVES: The aim of this study was to assess the positive surgical margin (PSM) and nerve sparing (NS) rates in patients who underwent prostate MRI (pMRI) prior to radical prostatectomy (RP) and compare them with matched, nonimaged control RP patients. METHODS: We identified 204 men who underwent preoperative pelvic MRI (pelMRI), of whom 176 (86.3%) underwent pMRIs, within 60 days of RP, and compared them (1:1) with a nonim-aged control group matched by surgeon, age, race, body mass index (BMI), prostate-specific antigen (PSA), pathological Gleason score, prostate specimen weight, and RP year. RESULTS: The rates of nonfocal extracapsular extension (nfECE) on RP pathology in the MRI and control groups were similar. PSM rates were lower in the MRI group (13.7% vs 19.3%; P=0.14), but the difference did not meet statistical significance; this was also the case in patients with nfECE on RP pathology (27.7% vs 39.5%; P=0.3). NS rates were similar between groups. In the MRI group, 54 (26.5%) patients had an MRI suspicious for nfECE; their PSM rate (20.4%) was higher than that of patients with an MRI not suspicious for nfECE (11.3%; P=0.11), but the difference lacked statistical significance; the former group had significantly lower rates of NS. Limitations of the study include sample power and nonuniform heeding of MRI results by each surgeon. CONCLUSION: MRI did not significantly decrease the rates of PSM, including in the subset of patients with nfECE on final pathology. Even wider resection may be necessary in patients with MRIs suggesting locally-advanced disease. Studies with greater power are needed.

Longer average blood storage duration is associated with increased risk of infection and overall morbidity following radical cystectomy.

BACKGROUND: Patients with bladder cancer undergoing radical cystectomy (RC) experience high rates of perioperative blood transfusions (PBTs) and morbidity. The aim of this study was to evaluate the effect of blood storage duration on the risk of adverse perioperative outcomes in this high-risk patient population. MATERIALS AND METHODS: In a retrospective review of RC patients from 2010 to 2014 who received PBTs, the average storage duration for all units transfused was used to classify patients as receiving older blood using 3 different definitions (≥21 days,≥28 days, and≥35 days). Multivariable Poisson regression models were used to determine the adjusted relative risk of perioperative infections and overall morbidity in those given older blood compared to fresher blood. RESULTS: Of the 451 patients undergoing RC, 205 (45%) received nonirradiated PBTs. In multivariable modeling, increasing average blood storage duration, as a continuous variable, was associated with an increased risk of infections (risk ratio [RR] = 1.08 per day, 95% CI: 1.01-1.17) and overall morbidity (RR = 1.08 per day, 95% CI: 1.01-1.15). Furthermore, ≥28-day blood storage (vs.<28) was associated with increased infections (RR = 2.69, 95% CI: 1.18-6.14) and morbidity (RR = 2.54, 95% CI: 1.31-4.95), and ≥35-day blood storage (vs.<35) was also associated with increased infections (RR = 2.83, 95% CI: 1.42-5.66) and morbidity (RR = 3.35, 95% CI: 1.95-5.77). CONCLUSIONS: Although blood is stored up to 42 days, storage≥28 days may expose RC patients to increased perioperative infections and overall morbidity compared with storage<28 days. Prospective cohort studies are warranted in cystectomy and other high-risk surgical oncology patients to better determine the effect of blood storage duration.

Infectious complications in transfused patients after radical cystectomy.

INTRODUCTION: Infectious complications are common after radical cystectomy (RC), and allogeneic blood transfusions may increase infection risk by an immunosuppressive effect. While it has been suggested that perioperative blood transfusion (PBT) may be associated with adverse oncologic outcomes after RC, no large analyses have assessed whether PBT increases the risk of perioperative infection after RC. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample (1998 to 2011) to study the rate of PBT during RC for bladder cancer and identify infectious complications. We compared rates of infectious complications in patients who did and did not receive PBT and developed a multivariable model to assess the independent risk of infectious complication associated with PBT controlling for age, year of surgery, obesity, chronic kidney disease, comorbidity score, and type of urinary diversion. RESULTS: We identified 126,454 RCs performed during the study period. A total of 34,203 (27%) received a PBT. The use of PBT increased over the study period, from 18.4% in 1998 to 31.6% in 2011 (p < 0.0001). Patients who received a PBT had an increased risk of perioperative infectious complications [36.7% versus 27.7%, unadjusted OR (95% CI) = 1.51 (1.43-1.60), p < 0.0001]. After adjusting for potential confounders, PBT remained an independent predictor of infectious complications [adjusted OR (95% CI) = 1.46 (1.38-1.55), p < 0.0001]. CONCLUSIONS: This analysis provides strong observational evidence that PBT is associated with an increased risk of perioperative infectious complications, which may be secondary to transfusion-related immunomodulation. Urologists should aggressively pursue blood conservation strategies and adhere to evidence-based restrictive transfusion thresholds, particularly given the rising rate of PBT.

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.

INTRODUCTION: Randomized controlled trials of platinum-based neoadjuvant chemotherapy (NAC) for bladder cancer have shown that patients who achieve a pathologic response to NAC exhibit 5 y survival rates of approximately 80-90% while NAC resistant (NR) cases exhibit 5 y survival rates of approximately 30-40%. These findings highlight the need to predict who will benefit from conventional NAC and the need for plausible alternatives. METHODS: The pre-treatment biopsy tissues from a cohort of 41 patients with muscle invasive bladder who were treated with NAC were incorporated in tissue microarray and immunohistochemistry for PD-L1, CD8, and FOXP3 was performed. Percentage of PD-L1 positive tumor cells was measured. Tumor-infiltrating lymphocytes (TIL) densities, along with CD8 and Treg-specific TILs, were measured. RESULTS: TIL density was strongly correlated with tumor PD-L1 expression, consistent with the mechanism of adaptive immune resistance in bladder cancer. Tumor cell PD-L1 expression was not a significant predictor of response. Neither was the CD8 nor Treg TIL density associated with response. Intriguingly though, the ratio of CD8 to Treg TIL densities was strongly associated with response (p = 0.0003), supporting the hypothesis that the immune system plays a role in the response of bladder cancer to chemotherapy. DISCUSSION: To our knowledge, this is the first report in bladder cancer showing that the CD8 to Treg TIL density in the pre-treatment tissues is predictive for conventional NAC response. These findings warrant further investigations to both better characterize this association in larger cohorts and begin to elucidate the underlying mechanism(s) of this phenomenon.

3-D Imaging and Simulation for Nephron Sparing Surgical Training.

Minimally invasive partial nephrectomy (MIPN) is now considered the procedure of choice for small renal masses largely based on functional advantages over traditional open surgery. Lack of haptic feedback, the need for spatial understanding of tumor borders, and advanced operative techniques to minimize ischemia time or achieve zero-ischemia PN are among factors that make MIPN a technically demanding operation with a steep learning curve for inexperienced surgeons. Surgical simulation has emerged as a useful training adjunct in residency programs to facilitate the acquisition of these complex operative skills in the setting of restricted work hours and limited operating room time and autonomy. However, the majority of available surgical simulators focus on basic surgical skills, and procedure-specific simulation is needed for optimal surgical training. Advances in 3-dimensional (3-D) imaging have also enhanced the surgeon's ability to localize tumors intraoperatively. This article focuses on recent procedure-specific simulation models for laparoscopic and robotic-assisted PN and advanced 3-D imaging techniques as part of pre- and some cases, intraoperative surgical planning.

Blood Transfusion is Associated with Increased Perioperative Morbidity and Adverse Oncologic Outcomes in Bladder Cancer Patients Receiving Neoadjuvant Chemotherapy and Radical Cystectomy.

PURPOSE: Perioperative blood transfusion (PBT) has been inconsistently associated with adverse outcomes. Bladder cancer patients are unique as they frequently undergo neoadjuvant chemotherapy (NAC) with resulting immunosuppression, which may be exacerbated by transfusion-related immunomodulation. We examined the effect of leukoreduced PBT on oncologic outcomes and perioperative morbidity in radical cystectomy (RC) patients who received NAC, quantifying exposure with a novel dose-index variable. METHODS: The Johns Hopkins Radical Cystectomy database was queried for patients who had undergone NAC followed by RC from 2010 to 2013. Overall, 119 patients had available PBT and survival data. A multivariable Cox model evaluated risk factors, including pathologic stage, Charlson Comorbidity Index, age, race, year of surgery, surgical margin status, PBT, and preoperative hemoglobin for bladder cancer-specific survival (CSS) and overall survival (OS). Logistic regression models determined factors that were independently associated with perioperative morbidity. RESULTS: Median follow-up was 7.8 months (range 0.2-41.8), and during follow-up there were 25 deaths and 21 cancer deaths. PBT significantly predicted OS (hazard ratio [HR] 1.26, 95 % confidence interval [CI] 1.07-1.49; p = 0.005), CSS (HR 1.32, 95 % CI 1.11-1.57; p = 0.002), and morbidity (odds ratio [OR] 1.67, 95 % CI 1.26-2.21; p = 0.004) in univariate analyses. In multivariable models, PBT was significantly associated with morbidity (OR 1.77, 95 % CI 1.30-2.39; p = 0.0002), but not OS or CSS. Intraoperative transfusion was associated with decreased OS and CSS, and increased morbidity, whereas postoperative transfusion was only associated with increased morbidity. CONCLUSIONS: Intraoperative blood transfusion was associated with increased perioperative morbidity and worsened OS and CSS in patients undergoing RC who had NAC. Although PBT may be life-saving in certain patients, a restrictive transfusion strategy may improve outcomes.