Subcentimeter pulmonary nodules are not associated with disease progression in patients with renal cell carcinoma.

PURPOSE: Renal cell carcinoma most commonly metastasizes to the lung. Indeterminate pulmonary nodules develop preoperatively in half of the patients with localized renal cell carcinoma but clinical significance remains poorly defined. We determined whether the presence of indeterminate pulmonary nodules, or nodule size or number is associated with renal cell carcinoma outcomes. MATERIALS AND METHODS: We reviewed data on 1,102 patients with renal cell carcinoma in whom chest computerized tomography was done within 6 months before nephrectomy from 2002 to 2012. Patients with metastatic disease at presentation, benign tumors, pulmonary nodules greater than 2 cm or concurrent pulmonary disease were excluded, leaving 748 available for analysis. Study outcomes included lung metastasis, any distant metastasis or death from renal cell carcinoma. Cox proportional hazards models were used to assess whether the presence of indeterminate pulmonary nodules, or nodule size or number was associated with outcomes. Models were evaluated by comparing discrimination using the Harrell c-index. RESULTS: Indeterminate pulmonary nodules were present in 382 of 748 patients (51%). Median followup was 4.1 years (IQR 2.2-6.1). The presence of indeterminate pulmonary nodules was not associated with distant metastasis or death from kidney cancer. However, compared to subcm indeterminate pulmonary nodules the nodules greater than 1 cm were associated with metastatic disease after adjusting for tumor histology, stage and size (HR 2.48, 95% CI 1.08-5.68, p = 0.031). The outcome c-index increased slightly after adding nodule size to a predictive model adjusted for tumor characteristics. CONCLUSIONS: No evidence in the current study suggested that indeterminate pulmonary nodules less than 1 cm are associated with renal cell carcinoma progression, although large nodules significantly predicted metastatic disease. Patients with subcm indeterminate pulmonary nodules would be unlikely to benefit from extensive postoperative chest imaging surveillance, which should be reserved for patients with nodules greater than 1 cm.

The Risks of Stone Diagnosis and Stone Removal Procedure After Different Bariatric Surgeries.

Introduction: Nephrolithiasis is common after malabsorptive bariatric surgery; however, the comparative risk of stone formation after different bariatric surgeries remains unclear. We seek to compare the risk of stone diagnosis and stone procedure after gastric banding (GB), sleeve gastrectomy (SG), short-limb Roux-en-Y (SLRY), long-limb Roux-en-Y (LLRY), and biliopancreatic diversion with duodenal switch (BPDDS). Patients and Methods: Using an administrative database, we retrospectively identified 116,304 patients in the United States, who received bariatric surgery between 2007 and 2014, did not have a known kidney stone diagnosis before surgery, and were enrolled in the database for at least 1 year before and after their bariatric surgery. We used diagnosis and procedural codes to identify comorbidities and events of interest. Our primary analysis was performed with extended Cox proportional hazards models using time to stone diagnosis and time to stone procedure as outcomes. Results: The adjusted hazard ratio of new stone diagnosis from 1 to 36 months, compared to GB, was 4.54 for BPDDS (95% confidence interval [CI] 3.66-5.62), 2.12 for LLRY (95% CI 1.74-2.58), 2.15 for SLRY (95% CI 2.02-2.29), and 1.35 for SG (95% CI 1.25-1.46). Similar results were observed for risk of stone diagnosis from 36 to 60 months, and for risk of stone removal procedure. Male sex was associated with an overall 1.63-fold increased risk of new stone diagnosis (95% CI 1.55-1.72). Conclusions: BPDDS was associated with a greater risk of stone diagnosis and stone procedures than SLRY and LLRY, which were associated with a greater risk than restrictive procedures. Nephrolithiasis is more common after more malabsorptive bariatric surgeries, with a much greater risk observed after BPDDS and for male patients.

Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients. DESIGN, SETTING, AND PARTICIPANTS: Targeted sequencing of 341 cancer genes at ∼540× coverage was performed on available tumor samples from 258 patients; 220 with clear cell histology (ccRCC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between somatic mutations and median first-line progression free survival (PFS1L) and overall survival were determined in metastatic ccRCC using Cox proportional hazards models and log-rank tests. RESULTS AND LIMITATIONS: Prevalent mutations (≥ 10%) were VHL (75%), PBRM1 (46%), SETD2 (30%), BAP1 (19%), KDM5C (15%), and PTEN (12%). With first-line everolimus, PBRM1 and BAP1 mutations were associated with longer (median [95% confidence interval {CI}] 12.8 [8.1, 18.4] vs 5.5 [3.1, 8.4] mo) and shorter (median [95% CI] 4.9 [2.9, 8.1] vs 10.5 [7.3, 12.9] mo) PFS1L, respectively. With first-line sunitinib, KDM5C mutations were associated with longer PFS1L (median [95% CI] of 20.6 [12.4, 27.3] vs 8.3 [7.8, 11.0] mo). Molecular subgroups of metastatic ccRCC based on PBRM1, BAP1, and KDM5C mutations could have predictive values for patients treated with VEGF or mTOR inhibitors. Most tumor DNA was obtained from primary nephrectomy samples (94%), which could impact correlation statistics. CONCLUSIONS: PBRM1, BAP1, and KDM5C mutations impact outcomes of targeted therapies in metastatic ccRCC patients. PATIENT SUMMARY: Large-scale genomic kidney cancer studies reported novel mutations and heterogeneous features among individual tumors, which could contribute to varied clinical outcomes. We demonstrated correlations between somatic mutations and treatment outcomes in clear cell renal cell carcinoma, supporting the value of genomic classification in prospective studies.

Surgical Treatment of Tumors Involving Kidneys With Fusion Anomalies: A Contemporary Series.

OBJECTIVE: To report a contemporary series of surgically treated patients with tumors involving kidneys with fusion anomalies. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all 10 patients treated at a single tertiary care institution for tumors involving kidneys with fusion anomalies between the years 2000 and 2015. One patient, diagnosed with lymphoma, did not undergo surgical treatment and was therefore excluded. Data regarding patient, tumor, and treatment characteristics were collected and described. RESULTS: The study cohort included 7 male and 2 female patients, at a median age of 52 years. Seven patients underwent open partial nephrectomy. Nephroureterectomy was performed on 2 patients; 1 open and 1 laparoscopic. All patients had localized disease at diagnosis. Tumor histologies were renal cell carcinoma in 5 patients, renal oncocytoma in 1 patient, urothelial carcinoma in 2 patients, and a well-differentiated liposarcoma involving the kidney in 1 patient. Accessory blood vessels were identified in 8 of 9 patients. Median estimated blood loss was 300 mL (interquartile range: 150-1000). Four patients had postoperative complications, including 3 major (Clavien grade ≥ 3) and 3 minor (Clavien grade ≤ 2) complications. During a median follow-up of 19.2 months (interquartile range: 3-34.8), 1 patient with urothelial carcinoma developed a bladder recurrence. None of the patients developed new-onset chronic kidney disease during the early postoperative period. CONCLUSION: Localized renal cortical tumors in kidneys with fusion anomalies may be treated with partial nephrectomy; however, complication rates are relatively high. Preoperative imaging of the blood vessels is necessary, as most patients have an accessory blood supply.

Partial and Radical Nephrectomy for Unilateral Synchronous Multifocal Renal Cortical Tumors.

OBJECTIVE: To evaluate clinicopathologic characteristics and treatment outcomes of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for unilateral synchronous multifocal renal tumors. METHODS: We retrospectively reviewed medical records for 128 patients with nonmetastatic, unilateral, synchronous, multifocal renal tumors who underwent surgical resection at our institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma were excluded. Differences between patient and tumor characteristics from the 2 nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival, overall survival, and chronic kidney disease upstaging were estimated using Kaplan-Meier methods. The log-rank test was used for group comparisons. RESULTS: The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17 of 95 planned PN (18%) were converted to RN. Tumor diameter and RENAL nephrometry scores were greater in RN patients (P <.0001 and P = .0002, respectively). Pathologic stage T3 was seen in 40% of RN patients and 10% of PN patients (P = .0002). Histologic concordance was apparent in 60 of 123 patients (49%). Median follow-up for patients alive without a recurrence was 4 years. Five-year recurrence-free survival was 98% for PN and 85% for RN. Five-year overall survival was 96% for PN and 86% for RN (P = .5). Five-year freedom from chronic kidney disease upstaging was 74% for PN and 55% for RN (P = .11). CONCLUSION: Partial nephrectomy for the treatment of unilateral, synchronous, multifocal, renal tumors with favorable characteristics was associated with a low recurrence rate. These findings suggest PN is an appropriate management strategy for this group of carefully selected patients.