E-cadherin is downregulated in benign prostatic hyperplasia and required for tight junction formation and permeability barrier in the prostatic epithelial cell monolayer.

BACKGROUND: We previously reported the presence of prostate-specific antigen (PSA) in the stromal compartment of benign prostatic hyperplasia (BPH). Since PSA is expressed exclusively by prostatic luminal epithelial cells, PSA in the BPH stroma suggests increased tissue permeability and the compromise of epithelial barrier integrity. E-cadherin, an important adherens junction component and tight junction regulator, is known to exhibit downregulation in BPH. These observations suggest that the prostate epithelial barrier is disrupted in BPH and E-cadherin downregulation may increase epithelial barrier permeability. METHODS: The ultra-structure of cellular junctions in BPH specimens was observed using transmission electron microscopy (TEM) and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate (FITC)-dextran in transwell assays. RESULTS: The number of kiss points in tight junctions was reduced in BPH epithelial cells as compared with the normal adjacent prostate. Immunostaining confirmed E-cadherin downregulation and revealed a discontinuous E-cadherin staining pattern in BPH specimens. E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation without affecting cell density. CONCLUSIONS: Our results indicate that tight junctions are compromised in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting targeting E-cadherin loss could be a potential approach to prevent or treat BPH.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

PURPOSE: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. MATERIALS AND METHODS: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. RESULTS: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. CONCLUSION: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

The comparative effectiveness of quadratus lumborum blocks and paravertebral blocks in radical cystectomy patients.

INTRODUCTION: Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay. RESULTS: Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p < 0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41). CONCLUSIONS: There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.

Small Renal Masses in Close Proximity to the Collecting System and Renal Sinus Are Enriched for Malignancy and High Fuhrman Grade and Should Be Considered for Early Intervention.

INTRODUCTION: Recent reports show a correlation between renal tumor radiographic characteristics and pathologic features. We hypothesize that a more central location within the relatively hypoxic renal medulla might confer a more aggressive tumor phenotype. To test this, radiographic tumor characteristics were compared with tumor grade and histology. MATERIALS AND METHODS: We retrospectively reviewed renal masses <4 cm in diameter that underwent resection between 2008 and 2013. Tumor location was recorded using standard R.E.N.A.L. Nephrometry Score. Multivariate logistic regression was performed to compare independent anatomic features with incidence of malignancy and high nuclear grade. RESULTS: A total of 334 renal tumors had information available for analysis. Univariate analysis showed that increasing endophycity and proximity to the collecting system (<4 mm) were predictors of malignancy and high-grade features. In multivariate analysis, proximity to the collecting system <4 mm remained the as the only anatomical variable predictive of malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.06-12.05; P = .04) and high nuclear grade (OR, 2.81; 95% CI, 1.44-5.51; P = .003). CONCLUSION: Malignancy and high tumor grade occur with much greater frequency when tumors are located deep in the kidney, in close proximity to the collecting system and renal sinus. Ninety-six percent of small renal masses in this region were cancers and nearly half were Fuhrman Grade 3 or 4, suggesting that these small centrally located tumors should be targeted for early intervention.

Preoperative immunonutrition prior to radical cystectomy: a pilot study.

INTRODUCTION: To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer. MATERIALS AND METHODS: We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups. RESULTS: There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses. CONCLUSIONS: Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.

Dorsal Lumbotomy Incision for Partial Nephrectomy in Patients With Small Posterior Renal Masses.

OBJECTIVE: To describe our single-surgeon experience with dorsal lumbotomy, an uncommonly utilized muscle-sparing incision, for open partial nephrectomy. MATERIALS AND METHODS: We retrospectively identified patients who underwent partial nephrectomy through dorsal lumbotomy incision by a single surgeon from September 2012 through April 2014. Clinicopathologic characteristics were recorded along with early postoperative outcomes including hospital length of stay and narcotic requirement. RESULTS: Twenty-four patients were identified for analysis. Median operative time was 71 minutes (interquartile range [IQR]: 63-91 minutes), and median estimated blood loss was 250 mL (IQR: 100-438 mL). Median length of stay was 1.2 days (IQR: 0.94-2.0 days) and median narcotic requirement was 17 mg of oral morphine equivalents (IQR: 4.9-43 mg). Overall perioperative complication rate was 25% including 1 major (Clavien III-V) complication. CONCLUSION: Partial nephrectomy via dorsal lumbotomy incision is a safe and feasible option for small posterior renal masses when performed by an experienced surgeon. The drawbacks of this approach are limited access to the renal hilum and risk of injury to the iliohypogastric or subcostal nerves. Dorsal lumbotomy is associated with postoperative outcomes equivalent to or better than standard operative approaches and should be considered a viable surgical approach in selected cases.

Total Psoas Area Predicts Complications following Radical Cystectomy.

Purpose. To determine whether total psoas area (TPA), a simple estimate of muscle mass, is associated with complications after radical cystectomy. Materials and Methods. Patients who underwent radical cystectomy at our institution from 2011 to 2012 were retrospectively identified. Total psoas area was measured on preoperative CT scans and normalized for patient height. Multivariable logistic regression was used to determine whether TPA was a predictor of 90-day postoperative complications. Overall survival was compared between TPA quartiles. Results. 135 patients were identified for analysis. Median follow-up was 24 months (IQR: 6-37 months). Overall 90-day complication rate was 56% (75/135). TPA was significantly lower for patients who experienced any complication (7.8 cm(2)/m(2) versus 8.8 cm(2)/m(2), P = 0.023) and an infectious complication (7.0 cm(2)/m(2) versus 8.7 cm(2)/m(2), P = 0.032) than those who did not. On multivariable analysis, TPA (adjusted OR 0.70 (95% CI 0.56-0.89), P = 0.003) and Charlson comorbidity index (adjusted OR 1.34 (95% CI 1.01-1.79), P = 0.045) were independently associated with 90-day complications. TPA was not a predictor of overall survival. Conclusions. Low TPA is associated with infectious complications and is an independent predictor of experiencing a postoperative complication following radical cystectomy.

Comparative hospital cost-analysis of open and robotic-assisted radical prostatectomy.

OBJECTIVE: To perform a contemporary comparative cost-analysis of robotic-assisted laparoscopic radical prostatectomy (RARP) and open radical retropubic prostatectomy (RRP). METHODS: All patients undergoing RARP (n = 115) or RRP (n = 358) by 1 of 4 surgeons at a single institution during a 15-month period were retrospectively reviewed. The hospital length of stay (LOS), operative time, hospital charges, reimbursement, and direct and indirect hospital costs were analyzed and compared. RESULTS: The mean LOS between patients undergoing RARP (1.2 ± 0.6 days) and RRP (1.4 ± 0.8 days) was not significantly different. The operating room supply costs per case were almost 7 times greater for RARP ($2852 ± $528) than for RRP ($417 ± $59; P < .05). The ancillary, cardiology, imaging, administrative, laboratory, and pharmacy costs were not significantly different between the 2 approaches. The mean total costs per case for RARP exceeded the total costs for RRP by 62% ($14 006 ± $1641 vs $8686 ± $1989; P < .05). Payment to the hospital from all sources was nearly equivalent: $10 011 for RRP and $9993 for RARP. Therefore, the average profit for each RRP was $1325 and each RARP lost $4013. CONCLUSION: In the present single-institution analysis, the total actual costs associated with RARP were significantly greater than those for RRP and were attributable to the robotic equipment and supplies.

Prostatic adenocarcinoma metastatic to pleomorphic liposarcoma, a "collision phenomenon": report of a case with review of pelvic collision tumors.

"Collision tumor" is an uncommon phenomenon characterized by coexistence of two completely distinct and independent tumors at the same site. Collision tumors have been reported in different sites in the body; however, these are particularly uncommon in the pelvic cavity. A 70-year-old man, with prior history of urothelial and prostate cancer, presented with a large pelvic mass detected on imaging studies. Pathological examination revealed a large liposarcoma with prostatic carcinoma embedded in it. Immunohistochemistry and florescence in situ hybridization studies were performed to reach to a conclusive diagnosis. To the best of our knowledge, this is the second case reported till date. We present the challenges encountered in the diagnosis of this case and review of pelvic collision tumors.

Glomus tumor of the kidney: case report and literature review.

Glomus tumor is a benign mesenchymal neoplasm of the subcutaneous tissue of the distal extremities and head and neck region. Glomus tumor rarely occurs in the visceral organs. This study reports the sixth case of a glomus tumor arising in the kidney in a 62-year-old man who presented with weight loss and an incidental kidney lesion detected by computed tomographic scan. Radiologically, the tumor was difficult to differentiate from a malignant lesion and was therefore excised by partial nephrectomy. The tumor was challenging to diagnose by routine hematoxylin and eosin microscopic examination, necessitating immunohistochemical analysis. Immunoreactivity was demonstrated for smooth muscle actin, vimentin, collagen IV, and CD57, with little to no expression of neuroendocrine, endothelial, or epithelial markers. To date, the tumor has followed a benign course without evidence of local recurrence or metastasis.

Adrenal insufficiency as presenting feature of non-Hodgkin lymphoma.

Lymphomatous involvement of an adrenal gland during the course of a lymphoma is common, but a primary presentation of adrenal insufficiency in a patient with lymphoma involving both adrenal glands is rare. We describe a 36-year-old man with non-Hodgkin lymphoma (NHL) who presented with adrenal insufficiency. His evaluation consisted of several imaging modalities, including positron emission tomography-computed tomography (PET-CT) scans, which were helpful in defining the extent of disease prior to treatment and in monitoring the patient's response to treatment. Our case illustrates the importance of preoperative evaluation to exclude a lymphoma, particularly in patients with bilateral renal and/or adrenal masses.

Resection of a staggering 36-cm angiomyolipoma.

Angiomyolipomas (AMLs) are benign tumours characterized by fat, smooth muscle and vascular components. Epithelioid AML is a recognized variant of AML that is comprised of epithelioid smooth muscle cells. We present a case of a 41-year-old male who presented with light-headedness, dizziness, right-sided abdominal pain and, on subsequent computed tomography, was found to have an enormous right kidney mass characteristic of an AML. The patient underwent preoperative selective arterial embolization followed by a right radical nephrectomy. The pathology revealed a 36-cm AML with focal epithelioid features. Although uncommon, AMLs can present as enormous retroperitoneal masses.

Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy.

BACKGROUND: Nephroureterectomy alone fails to adequately treat many patients with advanced upper tract urothelial carcinoma (UTUC). Perioperative platinum-based chemotherapy has been proposed but requires adequate renal function. OBJECTIVE: Our aim was to determine whether the ability to deliver platinum-based chemotherapy following nephroureterectomy is affected by postoperative changes in renal function. DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively reviewed data on 388 patients undergoing nephroureterectomy for UTUC between 1991 and 2009. Four institutions were included. INTERVENTION: All patients underwent nephroureterectomy. MEASUREMENTS: All patients had serum creatinine measured before and after surgery. The value closest to 3 mo after surgery was taken as the postoperative value (range: 2-52 wk). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation. eGFR values before and after surgery were compared using the paired t test. We chose an eGFR of 45 and 60 ml/min per 1.73 m(2) as possible cut-offs for chemotherapy eligibility and compared eligibility before and after surgery using the chi-square test. RESULTS AND LIMITATIONS: Our cohort of 388 patients included 233 men (60%) with a median age of 70 yr. Mean eGFR decreased by 24% after surgery. Using a cut-off of 60 ml/min per 1.73 m(2), 49% of patients were eligible for chemotherapy before surgery, but only 19% of patients remained eligible postoperatively. Using a cut-off of 45 ml/min per 1.73 m(2), 80% of patients were eligible preoperatively, but only 55% remained eligible after surgery. This distribution persisted when we limited the analysis to patients with advanced pathologic stage (T3 or higher). Patients older than the median age of 70 yr were more likely to be ineligible for chemotherapy both pre- and postoperatively by either definition, and they were significantly more likely to have an eGFR <45 ml/min per 1.73 m(2) postoperatively, regardless of their starting eGFR. This study is limited by its retrospective nature, and there was some variability in the timing of postoperative serum creatinine measurements. CONCLUSIONS: eGFR is significantly diminished after nephroureterectomy, particularly in elderly patients. These changes in renal function likely affect eligibility for adjuvant cisplatin-based therapy. Accordingly, we suggest strong consideration of neoadjuvant regimens.

Estimating postoperative mortality and morbidity risk of radical cystectomy with continent diversion using predictor equations.

PURPOSE: The POSSUM (Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity) and Portsmouth POSSUM predictor equations are scoring systems validated in the general surgery literature that estimate postoperative morbidity and mortality risk. We tested the validity of POSSUM and Portsmouth POSSUM in patients undergoing radical cystectomy with continent diversion. MATERIALS AND METHODS: We retrospectively reviewed physiological parameters, operative parameters, and 30-day morbidity and mortality in 102 patients who underwent radical cystectomy with continent orthotopic diversion, as done by a single surgeon. Predicted morbidity and mortality were calculated using the POSSUM and Portsmouth POSSUM equations. Patients were stratified into risk groups, and observed and predicted outcomes were compared. The accuracy of predictions was assessed using binomial and chi-square analysis. RESULTS: Observed mortality and morbidity rates were 2.9% and 34.3%, respectively. Predicted morbidity using POSSUM analysis was 46 compared to the 35 observed in our series (p = 0.01). Compared to 3 observed deaths predicted mortality using POSSUM and Portsmouth POSSUM analysis was 13 and 5 (p = 0.002 and 0.30, respectively). There was a significant lack of fit for the POSSUM model to predict morbidity and mortality (p <0.05). However, the mortality risk estimated by Portsmouth POSSUM was not significantly different from the observed mortality rate in our cohort. CONCLUSIONS: In our series the POSSUM equation over predicted morbidity and mortality, and was unsuitable for a comparative audit of patients who underwent radical cystectomy with continent diversion. The Portsmouth POSSUM equation allowed satisfactory prediction of mortality in our cohort and should be evaluated further in larger series.

Case of a concurrent renal mass and extragonadal retroperitoneal teratoma.

The presentation of a synchronous renal cell carcinoma (RCC) and germ cell tumor (GCT) is rare. We report the case of a 57 year-old male who presented with a right renal mass and retroperitoneal lymphadenopathy. He underwent a successful right partial nephrectomy and retroperitoneal lymph node dissection, and the subsequent pathology revealed a stage I clear cell RCC and a retroperitoneal teratoma with a component of benign prostatic tissue. We briefly discuss the rarity of this occurrence, the pathological features that helped support this diagnosis, and the likely etiologies of these synchronous lesions.

Management of bilateral synchronous renal cell carcinoma in a single versus staged procedure.

OBJECTIVES: The presentation of synchronous bilateral renal lesions is rare. We report our experience with the surgical management of these lesions in both a single and staged procedure. METHODS: We retrospectively reviewed the records of all patients with bilateral synchronous renal lesions who underwent surgical management by one surgeon between 2000-2007. We compared characteristics including pre and postoperative renal function, complication rates, and oncological outcomes between the single and staged cohorts. Data were analyzed using descriptive statistics, Student's t-test, and Fisher's exact test. RESULTS: A total of 26 patients (73% male, mean age 65.5 +/- 12.2 years) with bilateral synchronous lesions were identified with a mean follow-up of 25.9 +/- 19.7 months. Of these, 18 (69%) were performed as a single procedure, 5 (19%) were done as a staged procedure, and 3 (12%) had only the first part of the staged procedure performed. The single and staged cohorts were comparable in regards to preoperative creatinine (Cr) (1.1 +/- 0.4 mg/dl versus 1.1 +/- 0.2 mg/dl, p = 0.70), postoperative Cr (1.5 +/- 1.0 mg/dl versus 1.4 +/- 0.5 mg/dl, p = 0.73), and median hospital length of stay (HLOS) (5 days versus 4 days). The complication rate was 22% and 20% for the single and staged cohorts, respectively. One patient had a local recurrence and one patient developed metastatic disease in the single cohort versus no local recurrence or metastatic disease in the staged cohort. CONCLUSION: In the appropriate setting, surgical management of synchronous bilateral renal lesions can be done safely in a single procedure with comparable outcomes to those done in a staged manner.

Renal cell carcinoma containing fat without associated calcifications: two case reports and review of literature.

With rare exceptions, angiomyolipomas can be distinguished from malignant renal masses by the presence of macroscopic fat within the mass. We report 2 cases in which preoperative imaging with computed tomography was interpreted as diagnostic for angiomyolipoma, but the final pathologic analysis revealed clear cell renal cell carcinoma.