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.

Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy.

Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non-tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee-approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material-enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 µm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. (©) RSNA, 2016 Online supplemental material is available for this article.

Impact of a common clinical pathway on length of hospital stay in patients undergoing open and minimally invasive kidney surgery.

PURPOSE: Clinical pathways are designed to reduce variability in patient care practices and improve clinical outcomes. We evaluated the effect of implementing a clinical care pathway on length of stay in patients undergoing kidney surgery. MATERIALS AND METHODS: After receiving institutional review board approval we evaluated prospective data on consecutive cases of partial and radical nephrectomy performed at our institution from 2000 to 2011. We identified 1,775 partial nephrectomies (1,449 open and 326 minimally invasive) and 1,025 radical nephrectomies (857 open and 168 minimally invasive). We used multivariate linear regression to test for an interaction between procedure type and surgery before vs after the clinical pathway was begun. RESULTS: Median length of stay decreased 40% (from 5 to 3 days) for open surgery and 33% (from 3 to 2 days) for minimally invasive surgery after clinical pathway implementation. Length of stay in patients treated with minimally invasive or open partial nephrectomy and open radical nephrectomy decreased while it remained stable in those who underwent minimally invasive radical nephrectomy. The difference in length of stay between open and minimally invasive partial nephrectomy before and after implementing the clinical pathway decreased by 1.5 days (95% CI 0.56-2.5, p = 0.002). At 30 days postoperatively major complication rates remained similar. CONCLUSIONS: The clinical pathway resulted in a significantly shorter length of stay in patients treated with partial and radical nephrectomy without a discernible impact on safety or quality of care. Clinical pathways for kidney surgery should be used and continually optimized to enhance efficiency, patient safety and outcomes.

Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model.

OBJECTIVES: To test a novel porcine two-kidney model for evaluating the effect of controlled acute kidney injury (AKI) related to induced unilateral ischaemia on both renal units (RUs) To use neutrophil gelatinase-associated lipocalin (NGAL) and physiological serum and urinary markers to assess AKI and renal function. METHODS: Twelve female Yorkshire pigs had bilateral cutaneous ureterostomies placed laparoscopically with identical duration of pneumoperitoneum for all cases. An experimental group (n = 9) underwent induced unilateral renal ischaemia with left hilar clamping of timed duration (15, 30, 60 min) and a control group (n = 3) had no induced renal ischaemia. Urine was collected and analysed from each RU to assess creatinine and NGAL concentration preoperatively and at multiple postoperative time points. Serum was collected and analysed daily for creatinine and NGAL levels. Statistical comparisons were made using the rank-sum and sign-rank tests. RESULTS: Three pigs were excluded because of intra-operative and postoperative complications. In the RUs that experienced renal ischaemia (n = 7),the median urine volume was lower (P = 0.04) at 6, 12, 24 and 48 h and the median NGAL concentration was higher (P = 0.04) at 12 and 48 h compared with the RUs of control pigs that experienced no renal ischaemia (n = 2). When comparing the ischaemic (left) RU of the pigs in the experimental group with their contralateral non-ischaemic (right) RU, ischaemic RUs had a lower median cumulative urine volume at 6, 12, 24 and 48 h (P = 0.05) and a higher median NGAL concentration at 12, 24 and 48 h (P < 0.05). At 48 h, no significant increase was found in serum NGAL in pigs in the experimental group compared with controls (P = 0.2). Creatinine clearance (CC) was lower in ischaemic RUs compared with non-ischaemic RUs 1 day after surgery (P = 0.04) with decreasing CC as the duration of ischaemia increased. CONCLUSIONS: We have developed a promising novel small-scale pilot surgical model that allowed the evaluation of bilateral RU function separately during and after unilateral renal ischaemia. The induction of unilateral renal ischaemia corresponds with physiological changes in both the ischaemic and contralateral RU. AKI as measured by increases in NGAL and decreased renal function as measured by decreases in CC, are specific to the RU exposed to ischaemia.

Does large volume of distribution of lidocaine masks its systemic uptake from bladder?

PURPOSE: To assess whether therapeutic and toxic effects of intravesical lidocaine are determined by coincident serum levels. MATERIAL AND METHODS: Published clinical trials and case studies on instilled lidocaine 1-2% that reported serum lidocaine levels were analyzed using model independent pharmacokinetic equations to compute the absorbed dose fraction (F) for linear regression with the respective dwell times. RESULTS: Rapid absorption of intravesical lidocaine is evinced by the serum levels of 0.16±0.3 mg/L at 5 min in bladder cancer patients coinciding with the rapid onset of pain relief (<5 min) and blood pressure drop (≥10 mm Hg) in spinal cord injured patients. Serum levels at 5 min are raised five-fold by alkalinization for a tertiary amine with pKa of 7.8 and a linear rise in F with longer dwell time (r2 = 0.80; P<0.005) conforms to passive, paracellular diffusion of amphiphilic lidocaine (log P of 1.68) around umbrella cell borders with absorption rate at least five times faster than the terminal elimination rate, and therefore the delay in blood sampling after instillation is unwarranted. A rapid resolution of therapeutic and toxic effects is predicated on the extensive dilution of absorbed lidocaine with a rapid distribution half-life of 3.6 min in body weight dependent Vd - 15 times larger than blood volume, 0.13-4.5 L/kg which necessitates dose adjustment in children. CONCLUSION: Whether rapid absorption of instilled lidocaine is complicated by an equally rapid and extensive dilution in body weight dependent Vd can be resolved by early blood sampling (<30 min) for: evidence-based medicine, avoidance of lidocaine toxicity in children and to educate the evolution of lidocaine solution to gel and devices.

Intravesical Contrast-Enhanced MRI: A Potential Tool for Bladder Cancer Surveillance and Staging.

This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption. Instead of injection for DCE-MRI, intravesical contrast-enhanced MRI (ICE-MRI) instills Gadolinium chelate (Gadobutrol) together with trace amounts of superparamagnetic agents for measurement of tumor volume, depth, and aggressiveness. ICE-MRI leverages leaky tight junctions to accelerate passive paracellular diffusion of Gadobutrol (604.71 Daltons) by treading the paracellular ingress pathway of fluorescein sodium and of mitomycin (<400 Daltons) into bladder tumor. The soaring cost of diagnosis and care of bladder cancer could be mitigated by reducing the use of expensive operating room resources with a potential non-surgical imaging option for cancer surveillance, thereby reducing over-diagnosis and over-treatment and increasing organ preservation.

Renal function and oncologic outcomes of parenchymal sparing ureteral resection versus radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. MATERIALS AND METHODS: Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. RESULTS: Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. CONCLUSIONS: Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Methods for registration of magnetic resonance images of ex vivo prostate specimens with histology.

PURPOSE: To evaluate two methods of scanning and tissue processing to achieve accurate magnetic resonance (MR)-histologic correlation in human prostate specimens. MATERIALS AND METHODS: Two prostates had acrylic paint markers injected to define the plane of imaging and serve as internal fiducials. Each was placed on a polycarbonate plane-finder device (PFD), which was adjusted to align the imaging and cutting planes. Three prostates were aligned by use of a plane finder key (PFK), a polycarbonate plate that locks the specimen in a cylindrical carrier. Markers were injected for registration analysis. Prostates were imaged, then sectioned. Imaging software was used to create registration maps of the MR and histology images. Measurements between control points were made and compared. RESULTS: Accurate correlation was achieved between MR and histologic images. The mean displacement (MD) between the corresponding registration points using the PFD technique ranged from 1.11-1.38 mm for each section. The MD for all sections was 1.24 mm. The MD using the PFK technique ranged from 0.79-1.01 mm for each section, and the MD across all sections for the PFK was 0.92 mm. CONCLUSION: We describe two methods that can achieve accurate, reproducible correlation between MR imaging and histologic sections in human prostatectomy specimens.

Optimizing surgical outcomes in bladder cancer patients undergoing radical cystectomy.

Purpose: To evaluate predictors of high-quality surgery and their effect on surgical outcomes in patients with bladder cancer undergoing radical cystectomy. Evidence acquisition: A systematic and thorough review was performed to identify the most recent literature on current optimal management and predictors of high-quality surgery for patients undergoing radical cystectomy. Conclusions: Muscle-invasive bladder cancer is an aggressive cancer requiring efficient and high-quality surgery in order to achieve the best oncological outcomes. Negative surgical margins, number of lymph nodes resected, lymph node dissection template, and surgical volume have been associated with improved oncologic outcomes. Robotic radical cystectomy continues to evolve and recent randomized controlled trials have shown that oncological outcomes are non-inferior when compared to the open technique. Regardless of approach, surgical technique should continually be evaluated and refined to optimize outcomes in patients undergoing radical cystectomy.

Evidence-based comparison of robotic and open radical prostatectomy.

The rapid adoption of robotic-assisted laparoscopic radical prostatectomy (RALP) has occurred despite a lack of high-quality evidence demonstrating its oncologic advantages, safety, or cost effectiveness compared with open radical retropubic prostatectomy (ORP). This review examines the current literature comparing ORP and RALP, focusing on perioperative, oncologic, functional, and economic outcomes.

Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography.

PURPOSE: Computerized tomography has a critical role in the surveillance of stage I nonseminomatous germ cell tumors of the testis. Some protocols call for up to 16 computerized tomography scans over 5 years, thereby exposing young patients to a significant amount of radiation. We estimated the lifetime risk of cancer incidence and cancer death from imaging related radiation received during surveillance of stage I nonseminomatous germ cell tumor. MATERIALS AND METHODS: Using a model with a 64-slice computerized tomography scanner obtaining images of the abdomen and pelvis with or without chest in a standardized, phantom male patient, organ specific radiation doses were estimated using Monte Carlo simulation techniques. Lifetime attributable risks of cancer were estimated using the approach outlined in the Biological Effects of Ionizing Radiation VII Phase 2 report. RESULTS: With a 5-year surveillance protocol as suggested by the National Comprehensive Cancer Network, lifetime cancer risk ranged from 1 in 52 (1.9%) for an 18-year-old to 1 in 63 for a 40-year-old patient (1.2%). If chest computerized tomography is also performed the risk increases to 1 in 39 (2.6%) and 1 in 85 (1.6%), respectively. Lung and colon cancer accounted for most of the risk. The relative risk of a secondary malignancy with surveillance compared to a single scan after retroperitoneal lymph node dissection is approximately 15.2. CONCLUSIONS: Computerized tomography used in testicular cancer surveillance protocols imparts large radiation doses and is associated with a significant risk of cancer. This risk should be factored into counseling patients with stage I nonseminomatous germ cell tumor.

Optical biopsy of human bladder neoplasia with in vivo confocal laser endomicroscopy.

PURPOSE: Confocal laser endomicroscopy is a new endoscopic imaging technology that could complement white light cystoscopy by providing in vivo bladder histopathology. We evaluated confocal laser endomicroscopy by imaging normal, malignant appearing and indeterminate bladder mucosa in a pilot study. MATERIALS AND METHODS: Patients scheduled to undergo transurethral resection of bladder tumors were recruited during a 3-month period. After standard cystoscopy fluorescein was administered intravesically and/or intravenously as a contrast dye. A 2.6 mm probe based confocal laser endomicroscope was passed through a 26 Fr resectoscope to image normal and abnormal appearing areas. The images were collected with 488 nm excitation at 8 to 12 frames per second. The endomicroscopic images were compared with standard hematoxylin and eosin analysis of transurethral resection of bladder tumor specimens. RESULTS: Of the 27 recruited patients 8 had no cancer, 9 had low grade tumors, 9 had high grade tumors and 1 had a low grade tumor with a high grade focus. Endomicroscopic images demonstrated clear differences between normal mucosa, and low and high grade tumors. In normal urothelium larger umbrella cells are seen most superficially followed by smaller intermediate cells and the less cellular lamina propria. In contrast, low grade papillary tumors demonstrate densely arranged but normal-shaped small cells extending outward from fibrovascular cores. High grade tumors show markedly irregular architecture and cellular pleomorphism. CONCLUSIONS: We report the first study to our knowledge of in vivo confocal laser endomicroscopy in the urinary tract. Marked differences among normal urothelium, low grade tumors and high grade tumors were visualized. Pending further clinical investigation and technological improvement, confocal laser endomicroscopy may become a useful adjunct to conventional cystoscopy.

Comparison of Bladder Carcinogens in the Urine of E-cigarette Users Versus Non E-cigarette Using Controls.

Electronic cigarette (EC) use is gaining popularity as a substitute for conventional smoking due to the perception and evidence it represents a safer alternative. In contrast to the common perception amongst users that ECs represent no risk initial studies have revealed a complex composition of e-cigarette liquids. Conventional cigarette smoking is a known risk factor for developing bladder cancer and prior reports raise concern some of those causative compounds may exist in EC liquids or vapor. Urine samples were collected from 13 e-cigarette using subjects and 10 non e-cigarette using controls. Five known bladder carcinogens that are either present in conventional cigarettes, products of combustion, or solvents believed to be used in some e-cigarette formulations were quantified by liquid chromatography - mass spectrometry (LC-MS). Analysis of e-cigarette user urine revealed the presence of two carcinogenic compounds, o-toluidine and 2-naphthylamine, at a mean 2.3 and 1.3 fold higher concentration (p-value of 0.0013 and 0.014 respectively). Many of these subjects (9/13) were long term nonsmokers (>12 months). Further study is needed to clarify the safety profile of e-cigarettes and their contribution to the development of bladder cancer given the greater concentration of carcinogenic aromatic amines in the urine of e-cigarette users.

Aggressive surgical management of adenocarcinoma of the rete testis.

Adenocarcinoma of the rete testis is a rare and aggressive malignancy arising from the epididymal epithelium. We present a case of a 66-year-old male who presented with left testis mass. Histopathological analysis of orchiectomy specimen was consistent with adenocarcinoma of the rete testis. Subsequent retroperitoneal lymph node dissection revealed metastatic disease not detected on preoperative PET-CT. Prior reports have suggested poor response rates to both systemic chemotherapy and radiation therapy. Aggressive surgical management of the retroperitoneum should be considered even in clinically node-negative patients given the paucity of other effective treatment regimens.

An Inexpensive, Point-of-Care Urine Test for Bladder Cancer in Patients Undergoing Hematuria Evaluation.

Although hematuria (blood in urine) is the most common symptom of bladder cancer, 70-98% of hematuria cases are benign. These hematuria patients unnecessarily undergo costly, invasive, and expensive evaluation for bladder cancer. Therefore, there remains a need for noninvasive office-based tests that can rapidly and reliably rule out bladder cancer in patients undergoing hematuria evaluation. Herein, a clinical assay for matrix metalloproteinases ("Ammps") is presented, which generates a visual signal based on the collagenase activity (in urine of patients) on the Ammps substrates. Ammps substrates are generated by crosslinking gelatin with Fe(II) chelated alginate nanoparticles, which precipitate in urine samples. The cleavage of gelatin-conjugated alginate (Fe(II)) nanoparticles by collagenases generates free-floating alginate (Fe(II)) nanoparticles that participate in Fenton's reaction to generate a visual signal. In a pilot study of 88 patients, Ammps had 100% sensitivity, 85% specificity, and a negative predictive value (NPV) of 100% for diagnosing bladder cancer. This high NPV can be useful in ruling out bladder cancer in patients referred for hematuria evaluation.

Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome.

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.

Endoscopic spray cryotherapy for genitourinary malignancies: safety and efficacy in a porcine model.

OBJECTIVE: To examine the effects and safety of using endoscopic spray cryotherapy (ESC) on bladder, ureteral, and renal pelvis urothelium in a live porcine model. SUBJECTS AND METHODS: ESC treatments were systematically applied to urothelial sites in the bladder, ureter, and renal pelvis of eight female Yorkshire swine in a prospective trial. Freeze-thaw cycles ranged from 5 to 60 s/cycle for one to six cycles using a 7 French cryotherapy catheter. Tissue was evaluated histologically for treatment-related effects. Acute physiologic effects were evaluated with pulse oximetry, Doppler sonography, and postmortem findings. RESULTS: In bladder, treatment depth was inconsistent regardless of dose, demonstrating urothelial necrosis in one, muscularis propria depth necrosis in two, and full thickness necrosis in all remaining samples. In ureter, full thickness necrosis was seen in all samples, even with the shortest spray duration (5 s/cycle for six cycles or 30 s/cycle for one cycle). Treatment to the renal pelvis was complicated by adiabatic gas expansion of liquid nitrogen to its gaseous state, resulting in high intraluminal pressures requiring venting to avoid organ perforation, even at the lowest treatment settings. At a planned dose of 5 s/cycle for six cycles of the first renal pelvis animal, treatment was interrupted by sudden and unrecoverable cardiopulmonary failure after three cycles. Repeated studies replicated this event. Ultrasound and immediate necropsy confirmed the creation of a large gaseous embolism and reproducible cardiopulmonary effects. CONCLUSION: ESC in a porcine urothelial treatment model results in full-thickness tissue necrosis in bladder, ureter, and renal pelvis at a minimal treatment settings of 5 s/cycle for six cycles. Adiabatic gas expansion may result in fatal pyelovenous gas embolism and collateral organ injury, as seen in both animals receiving treatment to the renal pelvis in this study. These results raise safety concerns for use of ESC as a treatment modality in urothelial tissues with current device settings.

Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity.

BACKGROUND: The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear. OBJECTIVE: Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo. INTERVENTION: RC with mapping PLND. MEASUREMENTS: We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression. RESULTS AND LIMITATIONS: Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04-3.46], p=0.036; versus HR: 4.3 [95% CI, 2.25-8.34], p<0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10-42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22-54] and 35% [95% CI, 11-60], respectively). This study is limited by the lack of prospective randomization and a control group. CONCLUSIONS: The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.

Intraoperative mannitol use does not improve long-term renal function outcomes after minimally invasive partial nephrectomy.

OBJECTIVE: To evaluate intravenous mannitol during minimally invasive partial nephrectomy (PN) by comparing the renal function outcomes of the patients who received it versus those who did not. METHODS: Of 285 consecutive elective minimally invasive PN cases from February 2005 to July 2010, 164 patients (58%) were treated with mannitol. We compared the renal function recovery using a multivariate generalized estimating equation linear model of estimated glomerular filtration rate (eGFR) controlling for nephrometry complexity, preoperative eGFR, American Society of Anesthesiologists score, ischemia time, estimated blood loss, age, and sex. Sensitivity analyses were performed to adjust for cold ischemia and individual surgeon differences corrected for year of surgery. RESULTS: Of the 285 patients who underwent minimally invasive treatment, 164 received mannitol and 121 did not. Those who received mannitol had a better preoperative eGFR (median 72 vs 69 mL/min/m(2), P = .046), less complex nephrometry scores (P = 0.051), and were less likely to have an American Society of Anesthesiologists score of ≥ 3 (42% vs 54%, P = .005). Renal function recovery was similar in both groups (estimated effect of mannitol -0.7 mL/min/m(2), 95% confidence interval -3.6-2.2, P = .6). At no point in the postoperative period did mannitol make a significant difference in the eGFR according to the generalized estimating equation model after adjusting for multiple potential renal function confounders. CONCLUSION: Mannitol use did not influence renal function recovery within 6 months of minimally invasive PN as measured by the eGFR in our analysis. An appropriately designed prospective study of mannitol is being conducted to validate its use during PN.