Locally advanced solitary fibrous tumour of the prostate.

Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms composed of spindle cells, most often occurring in the pleura. SFTs arising from the prostate are exceptionally rare, with only around 40 cases reported in literature to date. We report a man in his 60s who was referred to our clinic for elevated prostate-specific antigen and presented with mild obstructive lower urinary tract and defecatory symptoms. Prostate needle-core biopsy revealed neoplastic spindle cells that strongly expressed CD34. Cross-sectional imaging demonstrated a 12 cm locally advanced heterogeneous prostate mass with intravesical extension and mass effect on the anterior rectum. Radical cystoprostatectomy with orthotopic neobladder reconstruction was performed, and the diagnosis of primary prostatic SFT was made based on histological characteristics and immunophenotyping. We present diagnostic, clinical management and prognostic considerations in patients with primary prostatic SFT.

Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer.

OBJECTIVE: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. MATERIALS AND METHODS: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. RESULTS: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CONCLUSION: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

PURPOSE: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. EXPERIMENTAL DESIGN: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. RESULTS: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). CONCLUSION: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters.

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.

Efficacy and safety of alvimopan use in benign urinary tract reconstruction.

PURPOSE: To analyze the use of alvimopan, a peripheral mu-opioid receptor antagonist, in expediting gastrointestinal recovery after benign abdominal urinary tract reconstruction. Alvimopan use has been well defined in the management of radical cystectomy and urinary diversion for oncologic indications. It has not been studied in benign abdominal genitourinary reconstruction. METHODS: Patients who underwent urinary reconstruction utilizing harvested bowel segments for benign conditions from 12/2014-7/2019 were retrospectively reviewed. From 5/2018-7/2019 our institution approved the use of perioperative alvimopan in the aforementioned patients (N = 11), who were paired 1:2 with patients from a cohort of alvimopan-eligible patients who did not receive the drug (N = 22). Patients were paired by (1) type of reconstruction and (2) presence of neurogenic bowel-bladder (NBB). RESULTS: Of the 70 patients who underwent urinary reconstruction during the study period, 46 patients (66%) were eligible to receive alvimopan. Length of stay was shorter for the alvimopan group compared to the non-alvimopan group (median 5 days [IQR 4-5 days] vs. 8 days [IQR 6-11 days]; P = 0.002). Time to first bowel movement was shorter for the alvimopan group (median 4 days [IQR 3-4 days] vs. 6 days [IQR 4-7], P = 0.001). No patient treated with alvimopan required a nasogastric (NG) tube for post-operative ileus compared to 7 (32%) patients in the non-treatment group (P = 0.035). Post-operative complications and 30-day readmissions were similar between the two groups. CONCLUSION: The use of perioperative alvimopan in benign abdominal urinary tract reconstruction expedited return of bowel function and decreased length of stay compared to a matched cohort of untreated patients.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Cystectomy for benign disease: readmission, morbidity, and complications.

INTRODUCTION: We sought to elucidate outcomes and risks associated with cystectomy and urinary diversion for benign urological conditions compared to malignant conditions. MATERIALS AND METHODS: We identified patients who underwent cystectomy and urinary diversion for benign and malignant diseases through the American College of Surgeons National Surgery Quality Improvement Program database for the period 2007-2015. Patients were selected for inclusion based upon their current procedure terminology and International Classification of Disease, Ninth revision codes. Primary outcome was 30 day morbidity including return to the operating room (OR); infectious, respiratory, and/or cardiovascular complications; readmission to the hospital; and mortality. Multivariable regression analyses were performed to identify associated factors. RESULTS: A total of 317 patients underwent cystectomy and urinary diversion for benign disease, and 5510 patients underwent radical cystectomy with urinary diversion for cancer. Rates of major morbidity (43.2% versus 38.6%), mortality (0.9% versus 1.9%), return to OR (5% versus 5.8%), readmission (19.7% versus 21.4%), postoperative sepsis (14.5% versus 12%), and wound complications (16.1% versus 14.2%) were similar among patients undergoing cystectomy for benign and malignant conditions. In the group with cystectomy for benign conditions, smoking (OR: 3.11) and longer operative duration (OR: 1.06) were significantly associated with increased overall morbidity. Wound complications were significantly higher in smokers (OR: 3.09) and with an ASA ≥ III (OR: 5.71) CONCLUSIONS: Patients undergoing cystectomy and urinary diversion for benign disease are at similar risk for 30 day morbidity and mortality as patients undergoing surgery for malignant conditions. Risk factors are identified that can potentially be targeted for morbidity reduction.

Optimization of Patient Selection for Neoadjuvant Chemotherapy in Muscle-invasive Urothelial Carcinoma of the Bladder.

BACKGROUND: Radical cystectomy (RC) is delayed in a subset of patients who respond poorly to neoadjuvant chemotherapy (NAC). The present study investigated the clinicopathologic characteristics predicting extravesical disease at RC and the factors associated with NAC tolerability to improve patient selection and the sequence of definitive therapy. MATERIALS AND METHODS: Patients with cT2 urothelial carcinoma of the bladder who underwent NAC were stratified by the final pathologic stage: complete (ypT0N0), partial (≤ pT2), and nonresponse (> pT2 and/or N+). Patients treated with upfront cystectomy were divided into those with organ-confined (≤ pT2) and those with extravesical disease (> pT2 and/or N+). RESULTS: Of 145 patients, 89 received NAC and 56 underwent upfront RC. The univariate predictors of extravesical disease in the patients treated with upfront RC included increased age (P = .021), higher Eastern Cooperative Oncology Group performance status (P < .001), hydronephrosis (P = .021), and cardiovascular risk factors. The complete, partial, and nonresponse rates to NAC were 25.8%, 39.3%, and 34.8%, respectively. The multivariate predictors of pathologic progression on NAC included low serum albumin (P = .005), hydronephrosis (P = .040), incomplete NAC (P = .014), and alternative NAC (non-gemcitabine/cisplatin or MVAC, P = .022). Significant multivariate predictors of incomplete NAC included increased age, coronary artery disease (P = .027), and Eastern Cooperative Oncology Group performance status. CONCLUSION: Redundant clinicopathologic features predicted adverse cystectomy pathology in patients treated with both NAC and upfront RC. The results of the present study demonstrated an inferior pathologic response to alternative NAC regimens in clinically organ-confined disease and implicated cardiovascular comorbidities and nutritional status in the tolerability and response to NAC. Our findings predicate the importance of using patient-specific factors to guide the sequence of definitive treatment toward timely, centralized care to improve clinical outcomes.

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells.

Dysregulation of transforming growth factor-ß1 (TGF-ß1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT). This study demonstrates that DZ-50 increased expression of the epithelial marker E-cadherin, and decreased the mesenchymal marker N-cadherin in human prostate cancer cells. In DU-145 cells, the effect of DZ-50 on EMT towards mesenchymal epithelial transition (MET) was inhibited by talin1 overexpression, a focal adhesion regulator promoting anoikis resistance and tumor invasion. DZ-50 treatment of human prostate cancer cells and cancer-associated fibroblasts (CAFs) downregulated IGFBP3 expression at mRNA and protein level. In TGF-ß1 responsive LNCaPTßRII, TGF-ß1 reversed DZ-50-induced MET by antagonizing the drug-induced decrease of nuclear IGFBP3. Furthermore, co-culture with CAFs promoted prostate cancer epithelial cell invasion, an effect that was significantly inhibited by DZ-50. Our findings demonstrate that the lead compound, DZ-50, inhibited the invasive properties of prostate cancer epithelial cells by targeting IGFBP3 and mediating EMT conversion to MET. This study integrated the mechanisms underlying the effect of DZ-50 and further supported the therapeutic value of this compound in the treatment of advanced metastatic prostate cancer.

Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1 in prostate cancer radioresistance.

INTRODUCTION: Epithelial-mesenchymal-transition (EMT) has been previously identified as a contributor to prostate cancer progression to metastasis and therapeutic resistance to antiandrogens and radiotherapy. In this study we conducted a retrospective analysis to investigate the significance of radiation-induced EMT and consequential changes to the tumor microenvironment in biochemical recurrence and response to radiotherapy in prostate cancer patients. METHODS: Expression profiling and localization for EMT effectors, E-Cadherin, N-Cadherin, ß-catenin and Vimentin was assessed in human prostate tumor specimens pre- and post-radiotherapy and correlated with biochemical recurrence. In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor specimens pre- and post-radiotherapy and correlated with pre-treatment prostate-specific antigen levels (PSA). RESULTS: Our findings identified that characteristic changes associated with the EMT phenotype and its reversal to mesenchymal-epithelial-transition (MET) within the tumor microenvironment correlate with biochemical recurrence and resistance to radiotherapy among prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor cells undergoing EMT implicates that DNA repair mechanisms may potentially reverse the cytotoxic effects of radiotherapy-induced DNA breaks. CONCLUSIONS: Our results suggest that EMT programming effectors, integrated with the actin cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide a signature of potential predictive significance of therapeutic response to radiotherapy in a subset of prostate cancer patients.

Prostate cancer polar localization on core biopsy predicts pathologic stage.

INTRODUCTION: This study investigated the polar sub-localization of prostate cancer on needle core biopsy ('polar' defined as tumor = 1 mm from the tissue polar edge) as a predictor of extraprostatic extension. MATERIALS AND METHODS: Histologic sections from 58 patients who underwent preoperative prostate biopsy and radical prostatectomy at the University of Kentucky from 2006 to 2013 were evaluated. Patients were retrospectively case matched based on pathologic stage (pT2 versus pT3/4) using biopsy Gleason grade and prostate-specific antigen. Histologic sections of needle core biopsies were analyzed for polar involvement. The location of polar involvement was correlated to the presence of extraprostatic extension on final prostatectomy pathology. RESULTS: Average percentage of total polar cores was predictive of extraprostatic extension on final prostatectomy, particularly in the prostatic apex and base (p = 0.029 and 0.006, respectively). Higher grade tumors were identified at the pole in the high stage cohort (p = 0.032). Total percent polar involvement had the greatest sensitivity and specificity for predicting extraprostatic extension when directly compared to previously described histologic parameters (percent greatest involvement of a single core, length of greatest involvement of a single core, presence of perineural invasion, presence of bilateral gland involvement, and percent total positive core involvement). The location of polar involvement on needle core biopsy was also predictive of the precise location of extraprostatic extension on final prostatectomy pathology (Chi-square p < .001, negative predictive value > 70% in all prostate sextants). CONCLUSIONS: These data suggest the use of biopsy polar core involvement as a valuable histologic predictor of increased pathologic stage.

Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer.

Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-ß mediates EMT programming and its phenotypic reversal to mesenchymal-epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study, we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-ß signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high-grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer.

Concomitant Renal Cell Carcinoma and Hematologic Malignancy in Immunosuppressed Patients.

OBJECTIVES: Treatment of a renal mass in patients with hematologic malignancy or on immunosuppression can be complex and is not well defined. Surgical excision or thermal ablation of renal mass is generally recommended in view of concern for tumor progression in immunosuppressed patients. We report our management decision experience in patients and literature review on concomitant renal and hematologic malignancy. MATERIALS AND METHODS: A retrospective medical record review of patients with renal cell carcinoma (RCC) and a hematologic malignancy over 3 years at our University Hospital was performed. Data were collected including patient׳s demographics, renal tumor and hematologic malignancy characteristics (stage, pathologic subtype, time of diagnosis, treatment type and prognosis). Surgical and medical management of each malignancy was reviewed and perioperative and overall outcomes are reported. RESULTS: In total, 6 patients were identified with RCC and a hematologic malignancy of which 4 were on immunosuppressive therapy. A total of 5 patients had leukemia and 1 patient had multiple myeloma. Most kidney tumors were stage I, 83%; and 80% were Fuhrman grade II. There was equal distribution of clear cell and papillary-type RCC. All but 1 patient had undergone nephron-sparing surgery. Overall, 50% of our patients died within 1 year after renal surgery for pT1a tumors from causes that are unrelated to renal cancer. CONCLUSIONS: Our small cohort showed significant mortality in patients with hematologic malignancy on immunosuppression, who had their renal mass treated with surgical excision or thermal ablation. However, this mortality was not secondary to surgical procedure itself. The prognosis of the hematologic malignancy might dictate the management of RCC.

Retropubic prostatectomy for giant benign prostatic hyperplasia.

Giant benign prostatic hyperplasia is a rare pathology of the prostate gland. Here we report the successful removal of the ninth largest prostate ever reported. This 65-year-old patient presented with acute urinary retention secondary to a bulky left prostatic mass identified on pelvic magnetic resonance imaging (MRI). His preoperative prostate-specific antigen (PSA) value was 44 ng/mL; preoperative biopsies were negative for malignancy. Open radical retropubic prostatectomy was performed and the resulting prostatic mass was measured at 13.5 cm x 11.5 cm x 5.2 cm, weighing 708 g including the prostate. The patient tolerated the procedure well. Surgical pathology showed no evidence of malignancy.

Trends in the management of male urethral stricture disease in the veteran population.

OBJECTIVE: To evaluate the relative use of urethral dilation, urethrotomy, and urethroplasty for male stricture disease in the Veterans Affairs (VA) population and examine trends over time in this cohort. METHODS: A retrospective chart review was performed using the VA Informatics and Computing Infrastructure database to access the Corporate Data Warehouse. The current procedural terminology codes were used to define a cohort of all men who underwent procedures for urethral stricture disease between October 1999 and August 2013. RESULTS: A total of 92,448 procedures were performed: 50,875 urethral dilations (55.03%), 39,785 urethrotomies (43.03%), and 1788 urethroplasties (0.19%). Over the course of the study, there was a shift in the management of male stricture disease. The relative percentage of urethral dilations performed decreased in each quintile (71.27, 58.03, 45.61, 44.39, and 38.67). The relative percentage of urethrotomies increased in each quintile (27.89, 40.80, 52.18, 53.04, and 56.95) as did the relative percentage of urethroplasties performed (0.85, 1.17, 2.21, 2.57, and 4.38). A total of 80.4% of these urethroplasties were performed in locations with a residency program. CONCLUSION: Although urethroplasty is still underused, there is a trend toward increased use of urethroplasty for male urethral stricture disease in the VA population. The majority of urethroplasties were performed at VA medical centers in locations with a residency program. We predict continued increases in utilization of urethroplasty for male urethral stricture disease as the number of fellowship-trained reconstructive urologists increases.

A 22-year-old female with invasive epithelioid angiomyolipoma and tumor thrombus into the inferior vena cava: case report and literature review.

A 22-year-old female presented with back pain and was discovered to have a right-sided abdominal mass. Computed tomography (CT) scan revealed a 9 cm enhancing right upper pole renal mass with suspicion for tumor thrombus into the right renal vein and possibly the inferior vena cava (IVC). Magnetic resonance imaging (MRI) confirmed tumor thrombus into the inferior vena cava approximately 3 cm below the hepatic venous confluence. Open right radical nephrectomy with inferior vena cava thrombectomy was performed with removal of right kidney and tumor thrombus en bloc. Pathology revealed malignant epithelioid angiomyolipoma (EAML or PEComa). Epithelioid angiomyolipoma is a rare tumor of mesenchymal tissue that has the potential for local invasion and disease progression. Diagnosis of EAML was confirmed by pathology and immunohistochemistry. She was referred to medical oncology for discussion of surveillance versus potential adjuvant therapy and ultimately opted for close surveillance.

Association of clinical and radiographic features with perinephric "sticky" fat.

BACKGROUND AND PURPOSE: The discovery of thick, adherent, perinephric sticky fat (PSF) is relatively common during open or laparoscopic retroperitoneal surgery. To our knowledge, however, there has been no previous analysis of clinical or radiographic features associated with the development of PSF or of perioperative outcomes for those patients in whom it is found. Our objective is to analyze potential predictive features and determine whether there is any effect on clinical or pathologic outcomes for patients with perinephric sticky fat. PATIENTS AND METHODS: Patients undergoing partial nephrectomy or laparoscopic cryoablation with available preoperative imaging were identified from 2005 to 2011. Operative records were reviewed to identify patients with and without PSF. Preoperative images and medical records were examined to obtain patient data regarding potential predictors as well as clinical and pathologic outcomes. RESULTS: A total of 29 patients were identified-16 with PSF and 13 controls. Statistically significant factors associated with PSF included sex, tumor size, presence of perinephric stranding, tumor >50% exophytic, and thickness of perinephric fat (P<0.05). Median total operative time for patients with sticky fat was nearly 40 minutes longer than the control group (228 min vs 190 min, P<0.05). All four (17%) patients with Fuhrman grade 3 or 4 renal-cell carcinoma were from the sticky fat group (P=0.09). CONCLUSIONS: Despite the small sample size, multiple possible factors associated with perinephric sticky fat were identified and may provide guidance for future investigation of this phenomenon.

Association of tumor size, location, R.E.N.A.L., PADUA and centrality index score with perioperative outcomes and postoperative renal function.

PURPOSE: Multiple scoring systems have been proposed to standardize the description of anatomical features of renal tumors. However, it remains unclear which of these systems, if any, is most useful, or whether any performs better than simply reporting tumor size or location in patients undergoing partial nephrectomy. To clarify these issues we evaluated the association of tumor size, location, R.E.N.A.L. (Radius/Exophytic/Nearness to collecting system/Anterior/Location), PADUA (Preoperative Aspects and Dimensions Used for an Anatomical classification) and centrality index scores with perioperative outcomes. MATERIALS AND METHODS: Patients undergoing partial nephrectomy with available preoperative imaging were identified from 2005 to 2011. R.E.N.A.L., PADUA and centrality index scores were assigned according to the described protocols for those systems. Associations between each variable and ischemia time, estimated blood loss, total operative time and change in estimated glomerular filtration rate were examined. RESULTS: A total of 162 patients were identified with a median tumor size of 3.1 cm (IQR 2.2 to 4.6). Median estimated blood loss, ischemia time and total operative time were 200 ml (IQR 100 to 300), 24 minutes (IQR 20 to 30) and 211 minutes (IQR 179 to 249), respectively. Each scoring system was found to have a statistically significant (p <0.001) correlation with ischemia time, with the centrality index system showing the strongest correlation. Furthermore, each of the scoring systems showed a stronger correlation with ischemia time than tumor size or tumor location. CONCLUSIONS: Each scoring system outperformed tumor size and location, and may be useful when describing the surgical complexity of renal tumors treated with partial nephrectomy.

5q Minus Myelodysplasia Associated with Multiple Epithelioid Granulomas within Conventional Renal Cell Carcinoma.

A 69-year-old Caucasian female, with a previous diagnosis of 5q minus myelodysplastic syndrome, presented with conventional renal cell carcinoma (RCC) associated with multiple-epithelioid nonnecrotizing granulomas. Two previous reports of sarcoidosis, primarily involving the lung and skin, have been described in patients with 5q minus myelodysplasia. A cluster of closely linked genes encoding for cytokines such as IL-4, IL-5, and IL-3 are present on chromosome 5q. Hence, in sarcoidosis, cytokine imbalances associated with the deletion of these cytokine genes have been postulated. However, an occurrence of epithelioid granulomas within a carcinoma, in preexisting clonal myelodysplastic syndrome, has not been described. The patient, in the current study, had long standing 5q minus deletion, clinically characterized by refractory anemia associated with hypolobated megakaryocytes. However, the patient's history was negative for sarcoidosis and the extensive nonnecrotizing epithelioid granulomas were confined within RCC. Due to the absence of Th-2 cytokines, such as IL-4 and IL-5, in a subset of 5q minus myelodysplastic syndrome, proinflammatory Th-1 cytokines such as IFN-γ and TNF-α may be exaggerated in an environment conducive to antigen expression. Hence, we propose a greater susceptibility for the development of granulomas, at least in a subset of patients with 5q minus myelodysplasia.