Successful Percutaneous Ultrasonic Lithotripsy of Gallstones.

Background: Acute calculous cholecystitis is the obstruction of the cystic duct by a gallstone that leads to inflammation of the gallbladder necessitating cholecystectomy. Case Series: We present the cases of 2 patients with acute calculous cholecystitis who were deemed ineligible candidates for cholecystectomy because of their complicating medical histories. Both patients initially underwent cholecystostomy and drain placement with interventional radiology for management of acute calculous cholecystitis. Their large gallstones remained refractory to attempts at removal by electrohydraulic lithotripsy via the cholecystostomy access. The patients' gallstones were successfully removed via percutaneous ultrasonic lithotripsy during a collaborative procedure with interventional radiology and urology. Conclusion: An interdisciplinary approach using percutaneous cholecystolithotomy with rigid ultrasonic lithotripsy is an effective method for removing challenging gallstones in patients for whom traditional approaches fail.

Diagnostic Accuracy of 99mTc-Sestamibi SPECT/CT for Characterization of Solid Renal Masses.

Our objective was to assess the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for characterizing solid renal masses. Methods: Imaging and clinical records of patients who underwent 99mTc-sestamibi SPECT/CT for clinical work-up of their solid renal masses from September 2018 to October 2021 were retrospectively reviewed. Histopathology formed the reference standard, and the diagnoses were categorized as malignant/concerning (renal cell carcinomas [RCCs] other than chromophobe histology) and benign/nonconcerning (oncocytic tumors including chromophobe RCC, other benign diagnoses) to calculate the sensitivity and specificity of 99mTc-sestamibi SPECT/CT and contrast-enhanced CT (ceCT). The clinical reads of the SPECT/CT images were used for visual classification of the lesions. Additionally, the SPECT images were manually segmented to obtain the maximum and mean counts of the lesion and adjacent renal cortex and maximum and mean lesion Hounsfield units. Results: 99mTc-sestamibi SPECT/CT was performed on 42 patients with 62 renal masses. A histopathologic diagnosis was available for 27 patients (18 male, 9 female) with 36 solid renal masses. ceCT findings were available for 20 of these patients. The most commonly identified single histologic type was clear cell RCC (13/36; 36.1%). Oncocytic tumors were the most common group of nonconcerning lesions (15/36), with oncocytoma as the predominant histologic type (n = 6). The sensitivity and specificity of SPECT/CT for diagnosing a nonconcerning lesion were 66.7% and 89.5%, respectively, compared with 10% and 75%, respectively, for ceCT. The lesion-to-kidney ratios for maximum and mean counts and maximum lesion Hounsfield units showed significant differences between the 2 groups (P < 0.05). The lesion-to-kidney mean count ratio at a cutoff of 0.46 showed a sensitivity and specificity of 87.5% and 86.67%, respectively, for detecting nonconcerning lesions, which was significantly higher than that of ceCT. Conclusion: The current literature on the utility of 99mTc-sestamibi SPECT/CT for characterization of solid renal masses is limited. We offer additional evidence of the incremental value of 99mTc-sestamibi SPECT/CT over ceCT for differentiating malignant or aggressive renal tumors from benign or indolent ones, thereby potentially avoiding overtreatment and its associated complications. Quantitative assessment can further increase the diagnostic accuracy of SPECT/CT and may be used in conjunction with visual interpretation.

Factors Associated with Ureteral Stent Failure in Patients with Malignant Ureteral Obstruction.

Introduction: Management of malignant ureteral obstruction (MUO) with ureteral stents remains a clinical challenge, often involving frequent stent exchanges attributable to stent failure or other urological complications. We report our institutional experience with ureteral stents for management of MUO, including analysis of clinical factors associated with stent failure. Methods: We performed a retrospective review of patients treated with indwelling ureteral stents for MUO in nonurothelial malignancies at our tertiary-care institution between 2008 and 2019. Univariate Cox proportional hazards analysis was performed to identify clinical variables associated with stent failure and stent-related complications. Stent failure was defined as need for unplanned stent exchange, placement of percutaneous nephrostomy (PCN), or tandem stents. Results: In our cohort of 78 patients, the median (range) number of stent exchanges was 2 (0-17) during a total stent dwell time of 4.3 (0.1-40.3) months. Thirty-four patients (43.6%) developed a culture-proven urinary tract infection (UTI) during stent dwell time. Thirty-five patients (44.8%) had stent failure. Twenty-two patients (28.2%) underwent unplanned stent exchanges, 23 (29.5%) required PCN after initial stent placement, and 6 (7.7%) required tandem stents. Ten (28.6%) patients with stent failure were treated with upsized stents, which led to resolution in seven patients. Stent failure occurred with 20/44 (45.4%) Percuflex™, 15/27 (55.6%) polyurethane, and 2/3 (66.7%) metal stents. In patients with ≥2 exchanges (N = 45), median time between exchanges was 4.1 (2.0-14.8) months. Bilateral stenting and history of radiation predicted UTI development. Median overall patient survival after initial stent placement was 19.9 months (95% CI 16.5-37.9 months). Conclusions: Ureteral stent failure poses a significant medical burden to patients with MUO. Better methods to minimize stent-related issues and improve patient quality of life are needed. Using a shared decision-making approach, clinicians and patients should consider PCN or tandem stents early in the management of MUO.

Contemporary Pure Laparoscopic vs Robot-Assisted Laparoscopic Radical Nephrectomy: Is the Transition Worth It?

Introduction: The proportion of robotic procedures continues to rise. The literature reinforces that robotic procedures take longer and are often more costly. We compared cost and perioperative outcomes of laparoscopic radical nephrectomy (LRN) and robot-assisted radical nephrectomy (RARN) at our high-volume center. Materials and Methods: We retrospectively reviewed our 2012-2015 data repository for patients undergoing RARN and LRN for a renal mass. Perioperative and oncologic outcomes were compared. We performed a multivariate analysis of operative time, estimated blood loss, length of stay (LOS), and overall and major 90-day complication rates while controlling for demographic data, Charlson comorbidity index (CCI), tumor size, and surgeon factors. We compared fixed, variable, and distinct procedural costs. Results: We identified 99 LRN and 95 RARN cases. There was no difference in demographic data, tumor size, preoperative renal function, and malignant histology. LRN patients had more comorbidities (49.5% vs 27.3% CCI 2+, p = 0.018). The mean preoperative glomerular filtration rate was higher in the robotic cohort (84.8 vs 75.1, p = 0.48). Mean operative time was 32.7 minutes longer (p = 0.002) and estimated blood loss 145 mL higher (p = 0.007) for the RARN cohort. There was no difference in mean LOS. Major and all 90-day complication rates were no different. The mean procedural cost for RARN was higher by $464 when controlling for operative time (p < 0.001). Fixed costs were not statistically different. Variable costs for RARN were estimated to be $2,310 higher (p = 0.045). Conclusions: Even with cost-conscious, experienced renal surgeons, RARN is associated with a longer procedure, higher supply costs, and higher hospitalization costs. There was no difference in positive surgical margin and complications. There were fewer 30-day readmissions for the RARN cohort, which may represent under-recognized cost savings. With fewer LRN cases in the United States each year, discussion to address cost is warranted. Without better outcomes for robotic surgery, a change in reimbursement to cover costs is unlikely to happen.

Does the sequence of high-dose rate brachytherapy boost and IMRT for prostate cancer impact early toxicity outcomes? Results from a single institution analysis.

BACKGROUND: We present the first report comparing early toxicity outcomes with high-dose rate brachytherapy (HDR-BT) boost upfront versus intensity modulated RT (IMRT) upfront combined with androgen deprivation therapy (ADT) as definitive management for intermediate risk or higher prostate cancer. METHODS AND MATERIALS: We reviewed all non-metastatic prostate cancer patients who received HDR-BT boost from 2014 to 2019. HDR-BT boost was offered to patients with intermediate-risk disease or higher. ADT use and IMRT target volume was based on NCCN risk group. IMRT dose was typically 45 Gy in 25 fractions to the prostate and seminal vesicles ± pelvic lymph nodes. HDR-BT dose was 15 Gy in 1 fraction, delivered approximately 3 weeks before or after IMRT. The sequence was based on physician preference. Biochemical recurrence was defined per ASTRO definition. Gastrointestinal (GI) and Genitourinary (GU) toxicity was graded per CTCAE v5.0. Pearson Chi-squared test and Wilcoxon tests were used to compare toxicity rates. P-value < 0.05 was significant. RESULTS: Fifty-eight received HDR-BT upfront (majority 2014-2016) and 57 IMRT upfront (majority 2017-2018). Median follow-up was 26.0 months. The two cohorts were well-balanced for baseline patient/disease characteristics and treatment factors. There were differences in treatment sequence based on the year in which patients received treatment. Overall, rates of grade 3 or higher GI or GU toxicity were <1%. There was no significant difference in acute or late GI or GU toxicity between the two groups. CONCLUSION: We found no significant difference in GI/GU toxicity in intermediate-risk or higher prostate cancer patients receiving HDR-BT boost upfront versus IMRT upfront combined with ADT. These findings suggest that either approach may be reasonable. Longer follow-up is needed to evaluate late toxicity and long-term disease control.

Incisional Lumbodorsal Hernias Following Retroperitoneal Robotic Partial Nephrectomies for Small Renal Masses at a High-Volume Tertiary Referral Center.

Introduction: Herein we evaluate the incidence of incisional lumbodorsal hernia (ILDH) after retroperitoneal robotic partial nephrectomy (RRPN) and associated patient-specific and tumor-specific risk factors. Furthermore, we aim to evaluate the role of routine lumbodorsal fascial closure for the prevention of ILDH. Methodology: This is a retrospective review of our robotic partial nephrectomy database of all RRPNs performed at Washington University School of Medicine from 2000 to 2020. Postoperative imaging was reviewed for evidence of ILDH. A clinically significant hernia was defined as the protrusion of visceral organ(s) through the lumbodorsal fascia. Patient and tumor characteristics, and fascial closure techniques were analyzed to determine predictors of ILDH. Results: In total, 150 patients underwent RRPN between 2007 and 2020 with an average follow-up of 4.9 (1-37) months. Twelve (8%) ILDHs were identified. Ten (6.7%) patients had herniated retroperitoneal fat whereas 2 (1.3%) patients had herniated colon. All were asymptomatic and managed conservatively. On matched cohort comparison, patients with ILDH had larger tumors than patients without an incisional hernia (3.9 cm vs 2.8 cm, p = 0.029). In general, patient factors were no different between patients with and without ILDH. However, coronary artery disease (CAD) was more prevalent in patients with ILDH (33.3% vs 10.9%, p = 0.028). Patients with ILDH were more likely to have a port site extended for specimen extraction (66.7% vs 38.2%, p = 0.069). Lumbodorsal fascial closure and type of suture material were not associated with prevention of ILDH (p = 0.545, p = 0.637). Conclusion: The radiographic incidence of lumbar incisional hernias after RRPN without routine fascial closure of the extraction incision was 8%. All were asymptomatic and did not require surgical repair. Larger tumor size and CAD were associated with ILDH.

Initial Experience with Single-Port Robot-Assisted Radical Cystectomy: Comparison of Perioperative Outcomes Between Single-Port and Conventional Multiport Approaches.

Background: The surgical techniques and devices used to perform radical cystectomy have evolved significantly with the advent of laparoscopic and robotic methods. The da Vinci® Single-Port (SP) platform (Intuitive Surgical, Inc., Sunnyvale, CA) is an innovation that allows a surgeon to perform robot-assisted radical cystectomy (RARC) through a single incision. To determine if this new tool is comparable to its multiport (MP) predecessors, we reviewed a single-surgeon experience of SP RARC. Materials and Methods: We identified patients at our institution who underwent RARC between August 2017 and June 2020 by one surgeon at our institution (n = 64). Using propensity scoring analysis, patients whose procedure were performed with the SP platform (n = 12) were matched 1:2 to patients whose procedure was performed with the MP platform (n = 24). Univariable analysis was performed to identify differences in any perioperative outcome, including operative time, estimated blood loss (EBL), lymph node yield, 90-day complication/readmission rates, and positive surgical margin (PSM) rates. Results: Patients who had an SP RARC on average had a lower lymph node yield than those who had an MP RARC (11.9 vs 17.1, p = 0.0347). All other perioperative outcomes, including operative time, EBL, 90-day complication rates, 90-day readmission rates, and PSM rates, were not significantly different between the SP and MP RARC groups. Conclusions: Based on their perioperative outcomes, the SP platform is a feasible alternative to the MP platform when performing RARC. The SP's perioperative outcomes should continue to be evaluated as more SP RARCs are performed.

Racial Comparison of Patients Undergoing Minimally Invasive Partial Nephrectomy for Renal Masses at a Large Volume Tertiary Center.

Introduction and Objective: African American (AA) race has been identified to have a higher incidence of chronic kidney disease (CKD) and worse renal cancer survival compared with Caucasian Americans (CA), irrespective of tumor size, pathologic type, and surgical procedure. We aimed to compare the outcomes between CA and AA patients undergoing minimally invasive partial nephrectomy (PN) at our high-volume center. Materials and Methods: We queried our PN data repository from 2007 to 2017. We identified 981 cases of PN (robotic n = 943 and laparoscopic n = 38), of which there were 852 CA and 129 AA patients. We compared age, sex, body mass index (BMI), operative time, estimated blood loss (EBL), nephrometry score, tumor size, pre- and postoperative estimated glomerular filtration rate (eGFR), length of stay, Charlson Comorbidity Index (CCI), tumor characteristics, and 30-day complication rate. We then estimated the overall survival and disease-specific survival. Results: Age, BMI, operative time, EBL, nephrometry score, tumor size, CCI, length of stay, and sex were not statistically different. The mean preoperative eGFR was higher in the AA cohort (91.4 mL/min/1.73 m2 vs 86.1 mL/min/1.73 m2, p = 0.007); however, at 1 year, there was no mean difference (76.8 mL/min/1.73 m2 vs 74.5 mL/min/1.73 m2, p = 0.428). There was a higher percentage of Fuhrman Grade 3/4 in the AA cohort (33.3% vs 22.5%, p = 0.044). The AA cohort had a 2.66 × higher incidence of papillary renal cell carcinoma (RCC) (34.9% vs 13.1%, p < 0.001) and unclassified RCC (3.9% vs 0.4%, p = 0.001). There was no difference in tumor stage (p = 0.260) or incidence of benign histology (15.3% vs 11.6%, p = 0.278). There were no differences in 30-day complications (p = 0.330). The median follow-up was 43.2 months. By using Kaplan-Meier curves, there was no observed difference in overall survival (p = 0.752) or disease-free survival (p = 0.403). Conclusions: Our cohort of AA and CA patients with intermediate follow-up showed no worse outcomes for CKD or survival when undergoing laparoscopic or robotic PN. For low-stage renal cancer, there was no difference in overall survival and disease-free survival at a median follow-up of 43.2 months among AA patients, despite having higher grade tumors and a higher percentage of unclassified RCC. Our cohort of AA patients did have a higher incidence of papillary RCC. The equivalent overall survival and disease-free survival could be due to the earlier discovery of lower stage renal masses incidentally identified on imaging studies performed equally for other reasons in both AA and CA patients.

Comparison of the Safety and Efficacy of Valveless and Standard Insufflation During Robotic Partial Nephrectomy: A Prospective, Randomized, Multi-institutional Trial.

OBJECTIVE: To use a randomized, prospective, multi-institutional study to compare the safety and efficacy of conventional insufflation (CIS) and valveless insufflation (AirSeal Insufflation - AIS) at the conventional pressure of 15 mm Hg in robot-assisted partial nephrectomy - a surgery where AIS has gained popularity for maintaining visualization despite suction. This study was also powered to evaluate the effect of decreasing pneumoperitoneum by 20% in the valveless system. MATERIALS AND METHODS: Three high-volume institutions randomized subjects into CIS 15, AIS 15, and AIS 12 mm Hg cohorts. Endpoints included rates of subcutaneous emphysema (SCE), pneumothorax (PTX), pneumomediastinum (PMS), intraoperative end-tidal carbon dioxide (ET CO2), and peak airway pressure (PAP), as well as hospital stay, post-operative pain, and complications. Given the substantial proportion of retroperitoneal surgery, a secondary analysis evaluated the effect of surgical approach. RESULTS: Two hundred and two patients were accrued. SCE was decreased in the AIS 12 mm Hg group (p=0.003). PTX and PMS rates were not statistically significantly different across the 3 insufflation groups. Higher rates of SCE and PMS, although not PTX, were noted in all retroperitoneal surgery groups - with lower SCE rates for AIS 12 mm Hg regardless of surgical approach. CONCLUSION: AIS is often preferred for complex procedures including retroperitoneal and transperitoneal robotic-assisted partial nephrectomy, for its maintenance of pneumoperitoneum despite continuous suction necessary for visualization. This study shows that AIS is safe when compared to CIS at 15 mm Hg, and shows improvement in outcomes when pneumoperitoneum pressure is reduced by 20% to 12 mmHg.

Predicting Adherent Perinephric Fat Using Preoperative Clinical and Radiological Factors in Patients Undergoing Partial Nephrectomy.

BACKGROUND: The decision to perform a partial nephrectomy (PN) relies largely upon the complexity of the renal mass and its surrounding anatomy. The presence of adherent perinephric fat (APF) can increase surgical complexity and extend operative times. The accurate prediction of APF may improve surgical planning and aid in decision making for the surgical approach. OBJECTIVE: We sought to develop and externally validate a score that predicts APF based on preoperative clinical and radiological prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed 495 consecutive patients who underwent open or minimally invasive PN. APF was defined as the presence of "dense," "adherent," or "sticky" perinephric fat at the time of dissection by the surgeon, and this did not require subcapsular dissection. Additionally, we analyzed an independent cohort of 285 patients for external validation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A score model was developed using multivariate logistic regression analysis. Calibration of the fitted model was assessed graphically with a plot of the predicted versus the actual probability of APF, and discrimination was assessed by calculating the area under the receiver operating characteristic curve. RESULTS AND LIMITATIONS: Of the 495 patients, 95 (19%) had APF. Patients with APF had longer operative (p=0.02) and arterial clamp (p=0.01) times than non-APF patients. On multivariate analyses, diabetes mellitus (p=0.009), posterior perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) were predictors of encountering APF in PN. A risk score ranging from 0 to 4 was developed based on these three variables to predict APF. The scoring system demonstrated good discrimination of 0.82 and 0.84 for the development and external validation cohorts, respectively. CONCLUSIONS: The APF score can accurately predict the presence of APF in patients with a small renal mass who are planning to undergo PN. This score could aid in pre- and intraoperative planning and impact the surgical approach. PATIENT SUMMARY: The presence of "sticky" fat surrounding the kidney in patients undergoing partial nephrectomy has previously been linked to longer operative times, intraoperative complications, and surgical conversion. In our study, we found that this feature is more often presented in patients with diabetes mellitus, and thicker and more inflammatory fat on renal imaging. Based on these findings, we developed a risk score that can accurately predict this feature before surgery, in order to improve surgical planning and better counsel the patients.

Ex Vivo Porcine Model for Robot-Assisted Partial Nephrectomy Simulation at a High-Volume Tertiary Center: Resident Perception and Validation Assessment Using the Global Evaluative Assessment of Robotic Skills Tool.

Introduction: With increased demands on surgeon productivity and outcomes, residency robotics training increasingly relies on simulations. The objective of this study is to assess the validity and effectiveness of an ex vivo porcine training model as a useful tool to improve surgical skill and confidence with robot-assisted partial nephrectomy (RAPN) among urology residents. Methods: A 2.5 cm circular area of ex vivo porcine kidneys was marked as the area of the tumor. Tumor excision and renorrhaphy was performed by trainees using a da Vinci Si robot. All residents ranging from postgraduate year (PGY) 2 to 5 participated in four training sessions during the 2017 to 2018 academic year. Each session was videorecorded and scored using the global evaluative assessment of robotic skills (GEARS) by faculty members. Results: Twelve residents completed the program. Initial mean GEARS score was 16.7 and improved by +1.4 with each subsequent session (p = 0.008). Initial mean excision, renorrhaphy, and total times were 8.2, 13.9, and 22.1 minutes, which improved by 1.6, 2.0, and 3.6 minutes, respectively (all p < 0.001). Residents' confidence at performing RAPN and robotic surgery increased after completing the courses (p = 0.012 and p < 0.001, respectively). Overall, residents rated that this program has greatly contributed to their skill (4/5) and confidence (4.1/5) in robotic surgery. Conclusions: An ex vivo porcine simulation model for RAPN and robotic surgery provides measurable improvement in GEARS score and reduction in procedural time, although significant differences for all PGY levels need to be confirmed with larger study participation. Adoption of this simulation in a urology residency curriculum may improve residents' skill and confidence in robotic surgery.

Ten-Year Experience with Percutaneous Cryoablation of Renal Tumors: Tumor Size Predicts Disease Progression.

Introduction: Percutaneous cryoablation (PCA) has emerged as an alternative to extirpative management of small renal masses (SRMs) in select patients, with a reduced risk of perioperative complications. Although disease recurrence is thought to occur in the early postoperative period, limited data on long-term oncologic outcomes have been published. We reviewed our 10-year experience with PCA for SRMs and assessed predictors of disease progression. Materials and Methods: We reviewed our prospectively maintained database of patients who underwent renal PCA from March 2005 to December 2015 (n = 308). Baseline patient and tumor variables were recorded, and postoperative cross-sectional imaging was examined for evidence of disease recurrence. Disease progression was defined as the presence of local recurrence or new lymphadenopathy/metastasis. Results: Mean patient age was 67.2 ± 11 years, mean tumor size was 2.7 ± 1.3 cm, and mean nephrometry score was 6.8 ± 1.7. At mean follow-up of 38 months, local recurrence and new lymphadenopathy/metastasis occurred in 10.1% (31/308) and 6.2% (19/308) of patients, respectively. Excluding patients with a solitary kidney and/or von Hippel-Lindau, local recurrence and new lymphadenopathy/metastasis occurred in 8.6% (23/268) and 1.9% (5/268) of cases, respectively. Kaplan-Meier estimated disease-free survival was 92.5% at 1 year, 89.3% at 2 years, and 86.7% at 3 years post-PCA. Increasing tumor size was a significant predictor of disease progression (hazard ratio 1.32 per 1-cm increase in size, p = 0.001). Conclusions: PCA is a viable treatment option for patients with SRMs. Increasing tumor size is a significant predictor of disease progression following PCA.

A Case Series of Delayed Proximal Ureteral Strictures After Nephron-Sparing Treatment of Renal Masses.

Background: Delayed proximal ureteral stricture (DPUS) after nephron-sparing treatment (partial nephrectomy [PN] and image-guided percutaneous ablation) of renal masses is a rare complication that occurs because of an unrecognized injury to the proximal ureter and/or its associated vascular supply. We present a multi-institutional series of patients who developed DPUS after nephron-sparing treatment and review relevant tumor characteristics, timing of DPUS presentation, presenting symptoms, and outcome of stricture management. Case Presentation: Between 2000 and 2019, nine patients (five PN and four ablation) were found to have DPUS diagnosed at an average of 9 (6-119) months after PN and 5.5 (1-6) after ablation. Average tumor size was 4.5 (2.9-7.3) cm and 3.6 (3-4.1) cm for those treated with PN and ablation, respectively. Nephrometry score was 8.3 (6-11) and 6.5 (5-8), respectively. For resected tumors, all were located in the lower pole, but uniformity was not found as far as medial vs lateral (3 vs 2), anterior vs posterior (2 vs 2, 1 N/A), and right vs left (3 vs 2). For ablated tumors, all four tumors were right sided, anterior, medial, and lower pole. Initial signs and symptoms include sepsis (2), flank pain (5), and asymptomatic hydronephrosis (2). Concomitant urinoma (2) and retroperitoneal abscess (1) was found on imaging. Initial management included ureteral stenting (5) and percutaneous nephrostomy tube (4). Three underwent nephrectomy. Two had spontaneous resolution of DPUS after a course of ureteral stenting. Conclusion: Potential risk factors associated with DPUS after nephron-sparing treatment, including medial and lower pole tumors, and particularly right-sided anterior masses for ablation and higher complexity nephrometry score for PN. Recognition of delayed symptoms and imaging abnormalities in the surveillance period should cue clinical suspicion to DPUS.

Ureteropelvic junction obstruction caused by metastatic cholangiocarcinoma.

We describe the rare case of a 61-year-old female with right ureteropelvic junction (UPJ) obstruction caused by metastatic cholangiocarcinoma. Her past medical history was notable for cholangiocarcinoma treated with neoadjuvant chemoradiation and two orthotopic liver transplants six years earlier. Urology was consulted when she presented with flank pain and urinary tract infection. Diagnostic workup demonstrated right UPJ obstruction. She was managed acutely with percutaneous nephrostomy. She subsequently underwent robotic pyeloplasty and intrinsic obstruction of the UPJ was discovered. Histological examination revealed adenocarcinoma, consistent with systemic recurrence of the patient's known cholangiocarcinoma.

Ureteropelvic junction obstruction caused by metastatic cholangiocarcinoma

ABSTRACT We describe the rare case of a 61-year-old female with right ureteropelvic junction (UPJ) obstruction caused by metastatic cholangiocarcinoma. Her past medical history was notable for cholangiocarcinoma treated with neoadjuvant chemoradiation and two orthotopic liver transplants six years earlier. Urology was consulted when she presented with flank pain and urinary tract infection. Diagnostic workup demonstrated right UPJ obstruction. She was managed acutely with percutaneous nephrostomy. She subsequently underwent robotic pyeloplasty and intrinsic obstruction of the UPJ was discovered. Histological examination revealed adenocarcinoma, consistent with systemic recurrence of the patient's known cholangiocarcinoma.

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer.

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P < 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted.

A propensity analysis comparing definitive chemo-radiotherapy for muscle-invasive squamous cell carcinoma of the bladder vs. urothelial carcinoma of the bladder using the National Cancer Database.

INTRODUCTION: Squamous cell carcinoma (SqCC) is the second most common histology of primary bladder cancer, but still very limited information is known about its treatment outcomes. Most bladder cancer trials have excluded SqCC, and the current treatment paradigm for localized SqCC is extrapolated from results in urothelial carcinoma (UC). In particular, there is limited data on the efficacy of definitive chemo-radiotherapy (CRT). In this study, we compare overall survival outcomes between SqCC and UC patients treated with definitive CRT. MATERIALS/METHODS: We queried the National Cancer Database (NCDB) for muscle-invasive (cT2-T4 N0 M0) bladder cancer patients diagnosed from 2004 to 2013 who underwent concurrent CRT. Propensity matching was performed to match patients with SqCC to those with UC. OS was analyzed using the Kaplan-Meier survival method, and the log-rank test and Cox regression were used for analyses. RESULTS: 3332 patients met inclusion criteria of which 79 (2.3%) had SqCC. 73.4% of SqCC patients had clinical T2 disease compared to 82.5% of UC patients. Unadjusted median OS for SqCC patients was 15.6 months (95% CI, 11.7-19.6) versus 29.1 months (95% CI, 27.5-30.7) for those with UC (P < 0.0001). On multivariable analysis, factors associated with worse OS included: SqCC histology [HR: 1.53 (95% CI, 1.19-1.97); P = 0.001], increasing age [HR: 1.02 (95% CI, 1.02-1.03); P < 0.0001], increasing clinical T-stage [HR: 1.21 (95% CI, 1.13-1.29); P < 0.0001], and Charlson-Deyo comorbidity index [HR: 1.26 (95% CI, 1.18-1.33); P < 0.0001]. Seventy-seven SqCC patients were included in the propensity-matched analysis (154 total patients) with a median OS for SqCC patients of 15.1 months (95% CI, 11.1-18.9) vs. 30.4 months (95% CI, 19.4-41.4) for patients with UC (P = 0.013). CONCLUSIONS: This is the largest study to-date assessing survival outcomes for SqCC of the bladder treated with CRT. In this study, SqCC had worse overall survival compared to UC patients. Histology had a greater impact on survival than increasing T-stage, suggesting that histology should be an important factor when determining a patient's treatment strategy and that treatment intensification in this subgroup may be warranted.

Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management?

OBJECTIVE: To evaluate the role of urine aquaporin 1 and perilipin 2 as biomarkers adjunct to renal mass biopsy in guiding the management of patients with small renal masses. METHODS: Preoperative aquaporin 1 and perilipin 2 levels in 57 patients with small renal masses undergoing partial nephrectomy were analyzed and compared with postoperative tumor histology. An algorithm was created utilizing aquaporin 1 and perilipin 2 in conjunction with renal mass biopsy. Cut-off values were implemented to maximize biomarker sensitivity and specificity. Renal mass biopsy utilization and intervention were then compared with rates in traditional renal mass biopsy algorithms. RESULTS: All clear cell and papillary renal cell carcinomas were correctly identified and assigned to the treatment path. All benign lesions were correctly sorted to a confirmatory renal mass biopsy path. Two chromophobe masses did not have elevated aquaporin 1 and perilipin 2, and would require renal mass biopsy. Compared with protocols that call for all small renal masses to be biopsied, confirmatory renal mass biopsy could have been safely avoided in 74% of patients with elevated aquaporin 1 and perilipin 2. Compared with protocols that do not utilize renal mass biopsy, surgical intervention would have been avoided in 23% of patients with benign masses. CONCLUSIONS: Aquaporin 1 and perilipin 2 possess high sensitivity and specificity for detecting clear cell and papillary renal cell carcinoma. Use of these markers might compliment renal mass biopsy in the characterization of small renal masses.

Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms.

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase in Apoa5 expression was controlled by the transcription factor CREBH, which coordinately regulated hepatic expression of fatty acid oxidation-related genes, including Fgf21 and Ppara. The CREBH-APOA5 axis activation upon PR was intact in mice lacking the GCN2-dependent amino acid-sensing arm of the integrated stress response. However, constitutive hepatic activation of the amino acid-responsive kinase mTORC1 compromised CREBH activation, leading to blunted APOA5 expression and PR-recalcitrant hypertriglyceridemia. PR also contributed to hypotriglyceridemia by reducing the rate of VLDL-TG secretion, independently of activation of the CREBH-APOA5 axis. Finally, a randomized controlled clinical trial revealed that 4-6 weeks of reduced protein intake (7%-9% of calories) decreased VLDL particle number, increased VLDL-bound APOA5 expression, and lowered plasma TGs, consistent with mechanistic conservation of PR-mediated hypotriglyceridemia in humans with translational potential as a nutraceutical intervention for dyslipidemia.