Management of Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy.

Perioperative complications of robot-assisted partial nephrectomy.

The incidence of renal cell carcinoma continues to increase with utilization of diagnostic abdominal imaging with migration towards a proportionally greater detection of small renal masses (SRM). Robot-assisted partial nephrectomy (RAPN) has become an attractive minimally invasive treatment modality for SRM's due to the technical advantages and shortened learning curve compared to laparoscopic partial nephrectomy (LPN) while preserving comparable perioperative outcomes. With advances in ablative approaches for stage I renal cell carcinoma (RCC) and controversy surrounding the role of extirpative surgery for SRM's, systematic understanding of the complications associated with RAPN has become even more imperative. This review aims to summarize and evaluate the contemporary literature, compile reported intraoperative complications, describe conventional and nephron-sparing surgery (NSS) specific postoperative complications, and assess factors associated with an increased likelihood for perioperative complications following RAPN.

Differential role of opioid receptors in tibial nerve inhibition of nociceptive and nonnociceptive bladder reflexes in cats.

Naloxone (an opioid receptor antagonist) was used to examine the role of opioid mechanisms in bladder reflexes and in somatic afferent inhibition of these reflexes by tibial nerve stimulation (TNS). Experiments were conducted in α-chloralose-anesthetized cats when the bladder was infused with saline or 0.25% acetic acid (AA). The bladder volume was measured at the first large-amplitude (>30 cmH(2)O) contraction during a cystometrogram and termed "estimated bladder capacity" (EBC). AA irritated the bladder, induced bladder overactivity, and significantly (P < 0.0001) reduced EBC to 14.3 ± 1.9% of the saline control. TNS (5 Hz, 0.2 ms) at 4 and 8 times the threshold (T) intensity for inducing an observable toe movement suppressed AA-induced bladder overactivity and significantly increased EBC to 41.5 ± 9.9% (4T, P < 0.05) and 46.1 ± 7.9% (8T, P < 0.01) of the saline control. Naloxone (1 mg/kg iv) completely eliminated TNS inhibition of bladder overactivity. Naloxone (0.001-1 mg/kg iv) did not change EBC during AA irritation. However, during saline infusion naloxone (1 mg/kg iv) significantly (P < 0.01) reduced EBC to 66.5 ± 8.1% of the control EBC. During saline infusion, TNS induced an acute increase in EBC and an increase that persisted following the stimulation. Naloxone (1 mg/kg) did not alter either type of inhibition. However, naloxone administered during the poststimulation inhibition decreased EBC. These results indicate that opioid receptors have different roles in modulation of nociceptive and nonnociceptive bladder reflexes and in somatic afferent inhibition of these reflexes, raising the possibility that opioid receptors may be a target for pharmacological treatment of lower urinary tract disorders.

Post-stimulation inhibitory effect on reflex bladder activity induced by activation of somatic afferent nerves in the foot.

PURPOSE: We determined whether transcutaneous electrical stimulation of somatic afferent nerves in the foot of cats would induce a post-stimulation increase in bladder capacity. MATERIALS AND METHODS: In 12 α-chloralose anesthetized cats electrical stimulation (5 Hz) was applied to the skin of the hind foot for 2, 30-minute periods via dual pad electrodes attached on the plantar and dorsal surfaces (combination 1 and 2) or at 2 sites on the plantar surface (combination 1 and 3). The post-stimulation effect was examined by repeat cystometrogram after 30-minute stimulation. In the control group of 12 cats isovolumetric contractions were allowed to continue during each 30-minute period without stimulation. RESULTS: Stimulation inhibited isovolumetric rhythmic bladder contractions. Bladder capacity was not increased after the first 30-minute foot stimulation via electrodes 1 and 2 but it was significantly increased a mean ± SE of 47.5% ± 2.9% after the second 30-minute stimulation via electrodes 1 and 3. After inducing the post-stimulation effect the foot stimulation applied during cystometrograms via electrodes 1 and 2 or 1 and 3 elicited a further increase in bladder capacity (mean 23.26% ± 17.64% and 20.07% ± 18.59%, respectively). CONCLUSIONS: Results show that the transcutaneous plantar electrical stimulation of somatic afferent nerves in the foot can induce a post-stimulation increase in bladder capacity, suggesting that an intermittent stimulation pattern rather than continuous stimulation might be effective as clinical application to treat overactive bladder symptoms.

Involvement of opioid receptors in inhibition of bladder overactivity induced by foot stimulation in cats.

PURPOSE: We examined the role of opioid receptors in the inhibition of bladder overactivity induced by electrical stimulation of the foot. MATERIALS AND METHODS: Experiments were done in 6 cats under α-chloralose anesthesia when the bladder was infused with saline or 0.25% acetic acid. Naloxone (1 mg/kg intravenously) was administered to block opioid receptors. To modulate reflex bladder activity electrical stimulation (5 Hz, 0.2 millisecond pulse width) was applied to the foot via skin surface electrodes at intensities of multiple times the threshold needed to induce observable toe movement. RESULTS: Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE 25.3% ± 5.9% that of saline control capacity (p = 0.0001). Foot stimulation at 4T suppressed acetic acid induced bladder overactivity and significantly increased bladder capacity to 47.1% ± 5.9% of control (p = 0.0007). Naloxone did not significantly change bladder capacity during acetic acid irritation but it completely eliminated the inhibition of bladder overactivity induced by foot stimulation. CONCLUSIONS: Results indicate that opioid receptors have an important role in foot afferent inhibition of bladder overactivity. This raises the possibility that opioid receptors might be used as a pharmacological target to enhance the efficacy of foot stimulation for inhibiting bladder overactivity.

Involvement of metabotropic glutamate receptor 5 in pudendal inhibition of nociceptive bladder activity in cats.

This study used MTEP, a metabotropic glutamate receptor 5 (mGluR5) antagonist, to examine the role of mGluR5 in the neural control of the urinary bladder and in the inhibition of the micturition reflex by pudendal nerve stimulation (PNS). Experiments were conducted in 11 female cats under α-chloralose anaesthesia when the bladder was infused with either saline or 0.25% acetic acid (AA). AA irritated the bladder, induced bladder overactivity and significantly (P < 0.001) reduced bladder capacity to 14.9 ± 10.3% of the saline control capacity. MTEP (0.1-50 mg kg(-1), i.v.) significantly (P < 0.05) increased bladder capacity during saline distension but not during AA irritation. However, MTEP induced a transient inhibition of isovolumetric bladder contractions under both conditions. PNS (5 Hz), which was tested at the threshold (T) intensity for inducing a complete inhibition of isovolumetric bladder contractions and at an intensity of 3-4T, suppressed AA-induced bladder overactivity and significantly increased bladder capacity to 68.0 ± 31.3% at 1T (P < 0.05) and 98.5 ± 55.3% at 3-4T (P < 0.01) of the saline control capacity. MTEP dose dependently (0.1-50 mg kg(-1), i.v.) suppressed PNS inhibition of bladder overactivity at low intensity (1T) but not at high intensity (3-4T). During saline infusion PNS significantly (P < 0.05) increased bladder capacity to 167.7 ± 27.1% at 1T and 196.0 ± 37.4% at 3-4T. These inhibitory effects were not observed after MTEP (0.1-50 mg kg(-1), i.v.) which also increased bladder capacity. These results indicate that glutamic acid has a transmitter function in bladder and somato-bladder reflex mechanisms and raise the possibility that mGluR5 may be a target for pharmacological treatment of lower urinary tract disorders.

Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults.

Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log(10)) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4(+) T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4(+) T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.

Robotic-assisted laparoscopic extravesical ureteroneocystostomy for management of adult ureteral duplication with upper pole prostatic urethral insertion.

A 55-year-old male presented with progressive lower urinary tract symptoms and renal colic. The workup revealed a complete left ureteral duplication with a hydronephrotic upper pole moiety inserting into the prostatic urethra. Using a 5-port transperitoneal robotic-assisted laparoscopic technique, an extravesical upper pole ureteroneocystostomy was performed. Clinical follow-up and repeat imaging documented symptomatic and radiographic improvement. Robotic-assisted laparoscopic reconstructive techniques are feasible and efficacious in the management of adult ureteral anomalies.

Is Ureteroscopy Needed Prior to Nephroureterectomy? An Evidence-Based Algorithmic Approach.

OBJECTIVE: To develop an evidence-based approach to the diagnostic workup of suspicious upper urinary tract lesions. METHODS: The PubMed database was searched using the following terms with a filter for English language: "upper tract urothelial carcinoma" and "upper tract transitional cell carcinoma," along with the following corresponding terms: "cost," "epidemiology," "diagnosis," "ureteroscopy," and "workup." A total of 404 articles were returned, and 33 were reviewed in full based on relevance. RESULTS: Computed tomography urogram is both sensitive and specific (96% and 99%). Cytology is utilized for its specificity (89%-100%). Ureteroscopy and biopsy of an upper tract lesion can be helpful in equivocal cases but can pose challenges in terms of yield and eventual pathologic upstaging. Due to the high sensitivity and specificity of other noninvasive tests, ureteroscopy can be obviated in select cases. We assess the available evidence and devise an algorithm for the evaluation of an upper tract urothelial carcinoma lesion. CONCLUSION: Ureteroscopy can be omitted as part of the diagnostic workup in appropriately selected cases of upper tract urothelial carcinoma.

Is extended preoperative antibiotic prophylaxis for high-risk patients necessary before percutaneous nephrolithotomy?

PURPOSE: The goal of this study was to compare the rate of systemic inflammatory response syndrome (SIRS) in high-risk patients undergoing percutaneous nephrolithotomy (PCNL) between patients who received 7, 2, or 0 days of preoperative antibiotics. MATERIALS AND METHODS: We retrospectively reviewed a series of consecutive PCNLs performed at our institution. Patients with infected preoperative urine cultures were excluded. High-risk patients were defined as those with a history of previous urinary tract infection (UTI), hydronephrosis, or stone size ≥2 cm. Patients were treated with 7, 2, or 0 days of preoperative antibiotic prophylaxis prior to PCNL. All patients received a single preoperative dose of antibiotics within 60 minutes of the start of surgery. Fisher exact test was used to compare the rate of SIRS by preoperative antibiotic length. RESULTS: Of the 292 patients identified, 138 (47.3%) had sterile urine and met high-risk criteria, of which 27 (19.6%), 39 (28.3%), and 72 (52.2%) received 7, 2, and 0 days of preoperative antibiotics, respectively. The 3 groups were similar in age, sex, and duration of surgery (p>0.05). There was no difference in the rate of SIRS between the groups, with 1 of 27 (3.7%), 2 of 39 (5.1%) and 3 of 72 patients (4.2%) meeting criteria in the 7, 2, and 0 days antibiotic groups (p=~1). CONCLUSIONS: Extended preoperative antibiotic prophylaxis was not found to reduce the risk of SIRS after PCNL in our institutional experience of high-risk patients. For these patients, a single preoperative dose of antibiotics is sufficient.

Comparing Expert Reported Outcomes to National Surgical Quality Improvement Program Risk Calculator-Predicted Outcomes: Do Reporting Standards Differ?

INTRODUCTION: Expert-reported outcomes and complications may not reflect the standardized coding that can be provided by independent, third-party evaluations. The goal of this article is to compare expert-reported complications with standardized coding by the National Surgical Quality Improvement Program (NSQIP). The procedures evaluated were laparoscopic radical nephrectomy (LRN), robot-assisted radical prostatectomy (RARP), and radical cystectomy (RC). METHODS: The 10 largest LRN, RARP, and RC series were reviewed for reported complications. An index patient was derived from each series using patient demographic data. Index patients were entered into the NSQIP surgical risk calculator (SRC), which provides 11 predicted outcomes based on inputted data. SRC-predicted outcomes were compared with available complication rates in each series. RESULTS: Across the 30 studies, 172 out of 330 (52%) of NSQIP-provided outcome types were presented within expert manuscripts. Death and venous thromboembolism (VTE) were the most commonly reported (27 and 23 studies, respectively), whereas urinary tract infection (UTI) (9) and pneumonia (10) were the least commonly presented. Comorbidities and follow-up duration were reported in 8 out of 30 and 17 out of 30 studies, respectively. For LRN, the median number of reported outcomes was 3 (range 1-5). LRN experts demonstrated a shorter mean length of stay (LOS) (2.5 days, SD=1.7) (p<0.001). In RARP studies, a median of 7.5 (3-11) outcomes was reported. Experts outperformed NSQIP RARP predictions in serious complications (p<0.001), any complication (p<0.001), surgical site infection (p=0.025), UTI (p<0.001), and VTE (p=0.002). RC manuscripts reported a median of 7 (2-11) outcomes. RC experts had higher rates of serious complications (p<0.001), reoperation (p<0.001), and death (p<0.001) than predicted by SRC. CONCLUSION: The level of standardization in reporting of outcomes differs between expert series and NSQIP, thus making comparisons difficult.

Nonmodifiable factors and complications contribute to length of stay in robot-assisted partial nephrectomy.

INTRODUCTION/OBJECTIVE: Robotic-assisted partial nephrectomy (RPN) offers a mean length of stay (LOS) of 2 to 3 days. The purpose of this study is to determine the impact of modifiable and nonmodifiable risk factors on hospital LOS after RPN. PATIENTS AND METHODS: We retrospectively reviewed our prospectively maintained database to identify all patients undergoing RPN for localized tumors at five US centers from 2007 to 2013. Patient and tumor characteristics were compared among hospital LOS groups. Associated factors were modeled using univariate and multivariate cumulative logistic regression to determine factors predictive of hospital LOS. RESULTS: One thousand five hundred thirty-two patients were grouped into LOS 1 to 3 days (1298, 84.1%), LOS=4 days (133, 8.6%), and LOS >4 days (110, 7.2%). Patient demographics were similar between groups. Patients in the LOS=4 and LOS >4 day groups were more likely to have a higher Charlson comorbidity index score (mean 2.2, 3.1 and 3.8; p<0.001), higher nephrometry score (mean 7.1, 7.6, 7.8; p=0.0002), and larger tumors (mean 2.9, 3.6 and 3.5 cm; p<0.0001) than those in the LOS 1 to 3 day group. Significant differences in complication rates were observed when comparing LOS 1-3 (116, 8.9%), LOS=4 (40, 30%), and LOS >4 (59, 54%). According to the Clavien-Dindo classification of surgical complications, 11 grade 3 and 11 grade 4 complications occurred in patients with an LOS of 4 or more days (p<0.0001). Postoperative transfusion, deep vein thrombosis, pulmonary embolism, atrial fibrillation, dyspnea/atelectasis, ileus, and acute renal failure each significantly predicted a hospital LOS >4 days (p<0.001). CONCLUSION: 15.8% of patients undergoing RPN have an LOS of 4 days or more. Longer LOS was independently associated with higher Charlson index, nephrometry score (nonmodifiable factors), and perioperative complications (potentially modifiable). These data may be useful in perioperative counseling and payer precertification.

Preoperative predictors of malignancy and unfavorable pathology for clinical T1a tumors treated with partial nephrectomy: a multi-institutional analysis.

PURPOSE: To determine preoperative predictors associated with renal cell carcinoma (RCC) and unfavorable pathology in small renal masses treated with partial nephrectomy (PN). MATERIALS AND METHODS: PN records from 5 centers were retrospectively queried for patients with a clinically localized single tumor <4 cm on imaging (clinical T1a). Between 2007 and 2013, 1,009 patients met the inclusion criteria. Unfavorable pathology was defined as any grade III or IV RCC or tumors upstaged to pathologic T3a disease. Logistic regression models were used to determine preoperative characteristics associated with RCC and with unfavorable pathology. RESULTS: A total of 771 (76.4%) patients were found to have RCC and 198 (19.6%) had unfavorable pathology. On multivariate, bootstrap-adjusted logistic regression analysis, factors associated with the presence of malignancy were imaging tumor size ≥ 3 cm (odds ratio [OR] = 1.46; P = 0.040), male sex (OR = 1.88; P<0.0001), and nephrometry score ≥ 8 (OR = 1.64; P = 0.005). These same factors were independently associated with risk of unfavorable pathology: size ≥ 3 cm (OR = 1.46; P = 0.021), male sex (OR = 2.35; P<0.0001), and nephrometry score ≥ 8 (OR = 1.49; P = 0.015). The c statistic was 0.62 for the predicting malignancy and 0.63 for unfavorable pathology. CONCLUSIONS: In this multi-institutional cohort, male sex, imaging tumor size ≥ 3 cm, and nephrometry score ≥ 8 were predictors of RCC and adverse pathology following PN. These factors may assist in risk stratification and selective renal mass biopsy before decision making. Further studies are necessary to validate these findings.

Patients with pathologically proven renal disease have similar declines in renal function following robot-assisted partial nephrectomy.

OBJECTIVE: To determine if patients with pathological, medical renal disease, defined as evidence of pathological abnormalities indicative of renal damage in the non-neoplastic partial nephrectomy specimens, have worsened functional outcomes following robot-assisted partial nephrectomy (RPN). MATERIALS AND METHODS: Sixty patients with and 101 without pathologically proven renal disease on non-neoplastic renal specimens were evaluated for differences in postoperative outcomes following RPN. Multiple linear regression modeling assessed for factors influencing early and late declines in renal function. RESULTS: The two groups were similar in all preoperative parameters. Both patients with and without pathological renal disease had similar lengths of hospitalization, transfusions, and complication rates. The percent change in the glomerular filtration rate was similar for patients with and without pathological renal disease (-8.8% vs -12.2%, p=0.194). Patients with pathological renal disease had less chronic kidney disease (CKD) upstaging than patients without renal disease (18.3% vs 39.6%, p=0.006). Increasing age (p=0.030) and higher preoperative glomerular filtration rates (p=0.044) predicted worse late percentage declines in renal function, while increased warm ischemia time predicted late CKD upstaging (p=0.043). CONCLUSION: The presence of pathological renal disease in non-neoplastic renal tissue did not place patients at risk for worsened postoperative complications or renal function deterioration following RPN.

Management of Bladder Cancer following Solid Organ Transplantation.

Objective. Present our experience managing bladder cancer following liver and renal transplantation. Methods. Single institution retrospective review of patients diagnosed with bladder urothelial carcinoma (BUC) following solid organ transplantation between January 1992 and December 2007. Results. Of the 2,925 renal and 2,761 liver transplant recipients reviewed, we identified eleven patients (0.2%) following transplant diagnosed with BUC. Two patients with low grade T1 TCC were managed by TURBT. Three patients with CIS and one patient with T1 low grade BUC were treated by TURBT and adjuvant BCG. All four are alive and free of recurrence at a mean follow-up of 51 ± 22 months. One patient with T1 high grade BUC underwent radical cystectomy and remains disease free with a follow-up of 98 months. Muscle invasive TCC was diagnosed in four patients at a median of 3.6 years following transplantation. Two patients are recurrence free at 24 and 36 months following radical cystectomy. Urinary diversion and palliative XRT were performed in one patient with un-resectable disease. Conclusions. Bladder cancer is uncommon following renal and liver transplantation, but it can be managed successfully with local and/or extirpative therapy. The use of intravesical BCG is possible in select immunosuppressed patients.