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Abstract Background Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment. Methods We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and TCGA-KIRP (n = 291) cohorts. We evaluated the efficacy of SF and SF plus MU combination in RCC cells, HAS3-transfectants, endothelial-RCC co-cultures, and xenografts. Results RCC cells showed increased HAS3 expression. In the clinical and TCGA-KIRC/TCGA-KIRP cohorts, higher HAS3 levels predicted metastasis and shorter survival. At > 10-µM dose, SF inhibited HAS3/HA-synthesis and RCC cell growth. However, at ≤ 5-µM dose SF in combination with MU inhibited HAS3/HA synthesis, growth of RCC cells and endothelial-RCC co-cultures, and induced apoptosis. The combination inhibited motility/invasion and an HA-signaling-related invasive-signature. We previously showed that MU inhibits SF inactivation in RCC cells. While HAS3-knockdown transfectants were sensitive to SF, ectopic-HAS3-expression induced resistance to the combination. In RCC models, the combination inhibited tumor growth and metastasis with little toxicity; however, ectopic-HAS3-expressing tumors were resistant. Conclusion HAS3 is the first known target of SF in RCC cells. In combination with MU (human equivalent-dose, 0.6–1.1-g/day), SF targets HAS3 and effectively abrogates mRCC.

There is a paucity of management recommendations for patients with aggressive Diffuse large B cell lymphoma (DLBCL) of the bladder. A 57-year-old male patient presented with lower urinary tract symptoms underwent flexible cystoscopy and then bladder tumor biopsy. Through immediate staging CT scan, tumor and bone biopsies he was diagnosed with a 16 cm Stage IVa high-grade DLBCL. He was treated with DA EPOCH with only a partial response and was transitioned to R-ICE. For rarer presentations of bladder cancer during diagnostic cystoscopy there should be no delay in tumor imaging and involving medical oncology in early treatment decision making.

PURPOSE: Many urologists recommend a six-week time interval between a prostate biopsy and a total prostatectomy (TP) to allow the biopsy induced inflammation to subside. Our aim was to assess whether the time interval between prostate biopsy and TP has an impact on the surgical outcome. MATERIALS AND METHODS: A retrospective analysis was performed on data from patients who underwent a TP by a single surgeon from 1992 to 2008. The patients were divided into two groups according to the time interval between biopsy and TP, Group 1 ≤ 6 weeks and Group 2 > 6 weeks. Relevant perioperative variables and outcome were analyzed. RESULTS: 923 patients were included. There was a significant difference between the two groups in the surgeons' ability to perform a bilateral nerve sparing procedure. Those who had a TP within six weeks of the biopsy were less likely to have a bilateral nerve sparing procedure. No significant difference was noted in the other variables, which included Gleason score, surgical margin status, estimated blood loss, post-operative infection, incontinence, erectile function, and biochemical recurrence. CONCLUSIONS: TP can be safely performed without any increase in complications within 6 weeks of a prostate biopsy. However, a TP within six weeks of a biopsy significantly reduced the surgeon's perception of whether a bilateral nerve sparing procedure was performed.

PURPOSE: Renal cell carcinoma (RCC) has a propensity to propagate into the renal vein and inferior vena cava (IVC). Due to inherent differences in the venous anatomy of the right and left kidneys, tumor thrombus involvement of IVC may vary. The aim of this study is to compare clinical presentation and outcome of right vs. left RCC with IVC thrombus. MATERIALS AND METHODS: Patients who underwent radical nephrectomy and IVC thrombectomy between 1997 and 2008 were identified. All relevant data were collected and analyzed. Results: Eight-seven patients were included. Sixty patients (69%) had a right sided tumor. Mean tumor size was 10.2 (± 4) cm and was not significantly different on either side. Fifty-six percent of right sided tumors had level-III (intra-hepatic) or higher tumor thrombus, while 22% of left sided tumors had similar level thrombus extension (p < 0.0001). Nearly 50% of left sided tumors showed level-I thrombus compared to 10% of right side tumors. A comparison of age, estimated blood loss and transfusion rate was not significantly different. The recurrence free (p = 0.9) and disease specific survival (p = 0.4) were not significantly different between the right and left side tumors with IVC thrombus. Conclusion: A level-III IVC tumor thrombus is more frequently seen with a right side tumor. However, clinical and operative characteristics among the left and right sided tumors with IVC thrombus were not different. More significantly, recurrence rate and survival did not differ with the laterality of the tumor.

Purpose: Standard radical nephrectomy for large masses is significantly facilitated by liver transplantation techniques, which have been successfully employed over the last ten years at our institution. Large and locally-advanced urothelial carcinoma of the kidney with or without extension into the inferior vena cava is rare. The purpose of this study was to present the surgical management of large and locally-advanced urothelial tumors arising from the renal pelvis using liver transplantation techniques and to evaluate patient outcome. Materials and Methods: Diagnostic work-up and surgical management of 4 patients with large and locally-advanced renal urothelial carcinoma were retrospectively reviewed. Two out of four patients with urothelial carcinoma presented with inferior vena cava thrombus. Mean tumor size was 11.6 cm. All patients underwent surgery, 2 patients with the presumed diagnosis of renal cell cancer. Liver transplantation techniques were an integral part in all radical nephrectomies. Results: No intraoperative complications and postoperative mortality occurred. Mean operative time was 7.5 hours, estimated blood loss was 1.5 L, and an average of 4.8 units of blood was transfused intraoperatively. Three patients succumbed to cancer recurrence at a mean postoperative time of 6.3 months; 1 patient is still alive 24 months after surgery. Conclusions: Large and locally-advanced renal masses of urothelial origin can be successfully removed by a combination of radical nephrectomy with liver transplantation techniques. Since long-term outcome of such patients has been poor, accurate preoperative diagnosis is essential to consider neoadjuvant treatment and to plan nephroureterectomy.

Prostate cancer (PC) is one of leading cause of cancer related deaths in men. Various aspects of cancer epigenetics are rapidly evolving and the role of 2 major epigenetic changes including DNA methylation and histone modifications in prostate cancer is being studied widely. The epigenetic changes are early event in the cancer development and are reversible. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic marker. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs in PC treatment. In this review, we discuss epigenetic changes associated with PC and their potential diagnostic and therapeutic applications including future areas of research.

OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC) with orthotopic neobladder (NB) to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

Radical retropubic prostatectomy (RRP) is an operation historically associated with the potential for significant blood loss. Patients who refuse a blood transfusion, such as Jehovahs witnesses, may be only offered radiation therapy as potentially curative treatment for prostate cancer because of the potential for a transfusion. Intraoperative cell salvage (IOCS) is an effective blood managient strategy for patients who are not willing to accept predonated autologous or allergenic blood. We present our managient for Jehovah's Witness patients with clinically localized prostate cancer, iphasizing our blood managient approach. This is the first such report.

PURPOSE: The desirable outcomes after open radical prostatectomy (RP) for localized prostate cancer (PC) are to: a) achieve disease recurrence free, b) urinary continence (UC), and c) maintain sexual potency (SP). These 3 combined desirable outcomes we called it the "Trifecta". Our aim is to assess the likelihood of achieving the Trifecta, and to analyze the influencing the Trifecta . MATERIALS AND METHODS: A total of 1738 men with localized PC underwent RP from 1992-2007 by a single surgeon. The exclusion criteria for this analysis were: preoperative hormonal or radiation therapy, preoperative urinary incontinence or erectile dysfunction, follow-up less than 24 months or insufficient data. Post-operative Trifecta factors were analyzed, including biochemical recurrence (BR).. We defined: BR as PSA > 0.2 ng/mL, urinary continence as wearing no pads, and sexual potency as having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor. RESULTS: A total of 831 patients met the inclusion criteria. The mean age of the entire cohort was 59 years old. The median follow-up was 52 months (mean 60, range 24-202). The BR, UC and SP rates were 18.7%, 94.5%, and 71% respectively. Trifecta was achieved in 64% at 2 year follow-up, and 61% at 5 year follow-up. Multivariate analysis revealed age at time of surgery, pathologic Gleason score (PGS), pathologic stage, specimen weight, and nerve sparing (NS) were independent factors. CONCLUSIONS: Age at time of surgery, pathologic GS, pathologic stage, specimen weight and NS were independent predictors to achieve the Trifecta following radical prostatectomy. This information may help patients counseling undergoing radical prostatectomy for localized prostate cancer.

Objectives : Budd-Chiari syndrome (BCS) is a poorly understood entity in urology. It results from obstruction of the hepatic veins and the subsequent complications. It has been infrequently reported to be secondary to hepatic venous obstruction from invasion by an inferior vena cava (IVC) tumor thrombus in renal cell carcinoma (RCC). We report the largest known series of patients with RCC and BCS. Patients and Methods : Ten patients presented to a tertiary hospital with locally advanced RCC with IVC tumor thrombus. All were evaluated and had clinical or radiographic evidence of BCS. All underwent nephrectomy, IVC thrombectomy or ligation, and tumor removal from the hepatic veins. The perioperative and pathological factors were measured. These included estimated blood loss (EBL) and transfusions. Inpatient factors including duration of intubation, length of intensive care unit (ICU) stay, and overall length of stay (LOS) were recorded. The tumor-free status was evaluated. Results : The average age was 59 years. No intraoperative deaths occurred. Two intraoperative complications were noted. The mean EBL was 4244 cc; mean surgery length was 8 hours 12 minutes; and the mean ICU stay was nine days. The overall LOS averaged 13.25 days. One patient died postoperatively of sepsis and multisystem organ failure. One patient required reoperation for an abdominal wall hematoma caused by subcutaneous enoxaparin administration. Average follow-up was 28 months. Five patients are alive with no evidence of disease. Conclusions : Budd-Chiari syndrome is a rare entity in urology, with a potential for significant morbidity and mortality. Surgical excision of the primary tumor along with thrombectomy results in alleviation of BCS and improvement in the patient.

Upper urinary tract (UUT) transitional cell carcinoma (TCC) is relatively rare tumor. Approximately 0.7-4% of patients with primary bladder cancer develops UUT-TCC. The symptoms related to an UUT-TCC often occur with an advanced stage which leads one to emphasize a surveillance strategy to monitor the UUT to allow for an earlier diagnosis. Although the risk of UUT-TCC after bladder cancer is well established, there is a paucity of recommendations suggesting the optimal method and frequency of monitoring the UUT and there is no consensus among them. This article reviews the recommendations on monitoring the UUT in patients with bladder cancer.

Introduction: Chemotherapy was shown to improve survival in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The initiation and completion rates for perioperative chemotherapy are variable. Our aim is to compare the likelihood of initiating and completing neoadjuvant (NAC) and adjuvant chemotherapy (AC) in patients who underwent of RC for MIBC. Materials and Methods: We performed a retrospective analysis of patients who underwent RC between 1992 and 2011. NAC was advised for patients with clinical stage ≥T2, hydronephrosis, extensive lymphovascular invasion (LVI), or prostatic stromal invasion. Patients with ≥pT3 or lymph node metastases were considered for AC. Results: A total of 363 patients were considered for perioperative chemotherapy. Among the 141 patients who were offered NAC, 125 (88.6%) initiated NAC. A total of 222 were considered for AC, and 151 (68.0%) initiated AC (P < 0.001). In the NAC group, 118 (83.5%) completed planned number of cycles of chemotherapy and 7 (5.6%) did not complete the planned chemotherapy. In the AC group, 79 (35.5%) completed at least four cycles and 72 (47.3%) could not complete the planned cycles (P < 0.001). Conclusions: Patients with MIBC are more likely to initiate and complete NAC than AC.