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.

Computed Tomography and Magnetic Resonance Findings of Fat-Poor Angiomyolipomas.

INTRODUCTION: Approximately 5% of angiomyolipomas (AMLs) are classified as "fat poor" due to lack of visually detectable fat on imaging, making them difficult to distinguish from renal cell carcinoma. Recent investigations have proposed CT and MR imaging features suggestive of fat-poor AML (fp-AML). Herein, we determined the frequency of these features in a cohort of fp-AMLs by retrospective review of preoperative imaging. METHODS: A pathology database query from January 2005 to August 2013 identified 49 renal specimens of AML with available imaging. A retrospective review of all CT and MR images of these 49 cases was conducted. Cases with visually detectable fat on imaging were excluded. RESULTS: A total of 26 fp-AMLs were identified. Thirteen lesions had available unenhanced CT images, of which eight (62%) were hyperdense compared to the adjacent renal parenchyma, while five (38%) were isodense. Twenty lesions had enhanced CT images: 14 (70%) and 6 (30%) with homogeneous and heterogeneous enhancement, respectively. Of the nine lesions with enhanced MR sequences, five (56%) were homogeneously enhancing, and four (44%) were heterogeneously enhancing. Eight of nine (89%) lesions had hypointense signal intensity (SI) on T2-weighted MR sequences, while one (11%) had hyperintense SI. None of the eight lesions displayed a decrease in signal on fat-suppressed sequences. CONCLUSIONS: In this study, we confirmed common imaging features of fp-AML: high attenuation on unenhanced CT sequences, homogeneous enhancement on CT, and hypointensity on T2-weighted MR. When these features are present, a renal mass biopsy may be prudent.

Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.

OBJECTIVE: To evaluate the sensitivity and specificity of urine aquaporin 1 (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary renal cell carcinoma (RCC) by comparing urine concentrations of these unique biomarkers in patients with RCC, noncancer renal masses, bladder cancer, and prostate cancer. METHODS: From February 1, 2012, through October 31, 2012, preoperative urine samples were obtained from patients with a presumptive diagnosis of RCC based on an imaged renal mass, prostate cancer, or transitional cell bladder cancer. Imaged renal masses were diagnosed postnephrectomy­as malignant or benign­by histology. Urine AQP1 and PLIN2 concentrations were measured by using a sensitive and specific Western blot and normalized to urine creatinine concentration. RESULTS: Median concentrations of urine AQP1 and PLIN2 in patients with clear cell and papillary RCC (n=47) were 29 and 36 relative absorbance units/mg urine creatinine, respectively. In contrast, median concentrations in patients with bladder cancer (n=22) and prostate cancer (n=27), patients with chromophobe tumors (n=7), and patients with benign renal oncocytomas (n=9) and angiomyolipomas (n=7) were all less than 10 relative absorbance units/mg urine creatinine (Kruskal-Wallis test, P<.001 vs RCC for both biomarkers) and comparable with those in healthy controls. The area under the receiver operating characteristic curve ranged from 0.99 to 1.00 for both biomarkers. CONCLUSION: These results support the specificity and sensitivity of urine AQP1 and PLIN2 concentrations for RCC. These novel tumor-specific proteins have high clinical validity and high potential as specific screening biomarkers for clear cell and papillary RCC as well as in the differential diagnosis of imaged renal masses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00851994.

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.

Port site metastasis after surgery for renal cell carcinoma: harbinger of future metastasis.

PURPOSE: Port site metastasis is a rare occurrence after minimally invasive treatment for renal cell carcinoma. However, its prognostic implications are unclear because reports in the literature are heterogeneous in detail and followup. We clarify the significance of port site metastasis in cancer specific survival and broaden our understanding of this phenomenon. MATERIALS AND METHODS: A MEDLINE® search for published studies of renal cell carcinoma port site metastasis was performed. Contributing factors to port site metastasis, stage, Fuhrman grade, pathology, port site metastasis treatment method, followup protocol and long-term outcomes were collected. The corresponding authors of each publication were contacted to fill in details and provide long-term outcomes. We added 1 case from our recent experience. RESULTS: A total of 16 cases from 12 authors (including ourselves) were found. Of the 12 authors 8 were available for correspondence and 9 cases were updated. Eventual outcomes were available for 11 of the 16 cases and survival curves showed poor prognosis with a 31.8% overall 1-year survival rate. Of the 16 cases 12 were radical nephrectomy and 4 were partial nephrectomy, and 13 involved multiple metastases in addition to the port site metastasis. Nine of the cases had no identifiable technical reason for port site metastasis formation such as specimen morcellation, absence of entrapment or tumor rupture. These tumors were uniformly aggressive, Fuhrman grade 3 or higher. CONCLUSIONS: Port site metastasis after minimally invasive surgery for renal cell carcinoma is a rare occurrence with a poor prognosis. In most cases port site metastasis is not an isolated metastasis but instead is a harbinger of progressive disease. While technical factors can have a role in port site metastasis formation, it appears that biological factors like high tumor grade also contribute.

Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.

OBJECTIVE: To evaluate the trends in urine aquaporin-1 (AQP1) and perilipin 2 (PLIN2) concentrations in patients with clear cell and papillary renal cell carcinoma (RCC), we determined the relationship between the urine concentration of these biomarkers and tumor size, grade, and stage. MATERIALS AND METHODS: The biomarker concentrations were determined by sensitive and specific Western blot procedures normalized to the urine creatinine excretion. The analysis included 61 patients undergoing partial or radical nephrectomy for clear cell or papillary RCC and 43 age- and sex-matched control patients. Relationships between urine biomarker concentrations and tumor size, stage, and grade were assessed. RESULTS: Patients with RCC had 35-fold and 9-fold higher median urinary AQP1 and PLIN2 concentrations, respectively, compared with controls. Both tumor markers decreased after tumor resection to concentrations equivalent to those of controls. The sensitivity and specificity were both 100% for AQP1 and 92% and 100%, respectively, for PLIN2. A significant linear correlation was found between the tumor size and the prenephrectomy AQP1 (Spearman coefficient 0.78, P <.001) and PLIN2 (Spearman coefficient 0.69, P <.001) concentrations. A correlation was found for both markers with tumor stage (overall P = .030), when the stage was dependent primarily on the tumor size (stages T1 and T2), but not with stage T3, which reflected extrarenal spread. Neither marker showed a significant correlation with tumor grade. CONCLUSION: AQP1 and PLIN2 were significantly increased in patients with clear cell and papillary RCC compared with controls. The preoperative urinary concentrations of these markers reflected the tumor size and stage.

In vivo evaluation of a reverse thermosensitive polymer for ureteroscopy with laser lithotripsy: porcine model.

PURPOSE: To evaluate the effects of a reverse thermosensitive polymer during ureteroscopy with laser lithotripsy in an in vivo porcine model. MATERIALS AND METHODS: Six pigs underwent general anesthesia followed by bilateral ureteroscopy with laser lithotripsy of stone phantoms while measuring intrapelvic renal pressures through bilateral nephrostomy tubes. The procedures were performed in one ureter with the reverse thermosensitive polymer and in the contralateral, control ureter without the reverse thermosensitive polymer. Stone migration lengths, operative times, laser times, laser energy usage, intrapelvic pressures, and postnecropsy histologic examinations of the ureters were compared between the two groups. RESULTS: Bilateral ureteroscopy with lithotripsy was successfully performed in five of six pigs. In one pig, only the unilateral control was performed, because the ureter was too narrow to complete the contralateral side. The mean laser time was 12.8 minutes shorter with the use of the reverse thermosensitive polymer group than in the controls (P=0.021). The procedure time, laser energy usage, and retropulsion length was shorter in the reverse thermosensitive polymer group, but did not reach significance. Between the two groups, there was no difference in mean renal pelvic pressures, peak renal pelvic pressures, or postprocedure histologic examinations of the ureters. CONCLUSIONS: The use of a reverse thermosensitive polymer during ureteroscopy with lithotripsy may have greater advantages beyond preventing stone retropulsion. Here, the use of a reverse thermosensitive polymer during ureteroscopy with lithotripsy resulted in a significant decrease in laser times. Further clinical investigations could further delineate the advantages of using a reverse thermosensitive polymer during intracorporeal lithotripsy.

The second "time-out": a surgical safety checklist for lengthy robotic surgeries.

Robotic surgeries of long duration are associated with both increased risks to patients as well as distinct challenges for care providers. We propose a surgical checklist, to be completed during a second "time-out", aimed at reducing peri-operative complications and addressing obstacles presented by lengthy robotic surgeries. A review of the literature was performed to identify the most common complications of robotic surgeries with extended operative times. A surgical checklist was developed with the goal of addressing these issues and maximizing patient safety. Extended operative times during robotic surgery increase patient risk for position-related complications and other adverse events. These cases also raise concerns for surgical, anesthesia, and nursing staff which are less common in shorter, non-robotic operations. Key elements of the checklist were designed to coordinate operative staff in verifying patient safety while addressing the unique concerns within each specialty. As robotic surgery is increasingly utilized, operations with long surgical times may become more common due to increased case complexity and surgeons overcoming the learning curve. A standardized surgical checklist, conducted three to four hours after the start of surgery, may enhance perioperative patient safety and quality of care.

Gas-producing renal infection presenting as pneumaturia: a case report.

We present a case of persistent pneumaturia of one-year duration in a fifty-five-year-old male with a history of spinal cord injury. The evaluation demonstrated gas throughout the collecting system attributable to a urinary tract infection with a gas-forming organism, Klebsiella pneumoniae.

Fibroepithelial polyp of the ureter presenting incidentally in a patient with a diverticular abscess.

We report on a patient with a fibroepithelial polyp of the distal ureter in whom the diagnosis was made incidentally while being examined for a diverticular abscess draining into the vagina. This patient's lack of symptoms and a possible relationship with the diverticular abscess is also explored.