Anthony T. Corcoran

Assessing the burden of complications after surgery for clinically localized kidney cancer by age and comorbidity status.

OBJECTIVEnTo examine the association between high-risk patient status (age >75 years or Charlson comorbidity index count >2) and postoperative complications in patients undergoing surgical management for clinically localized renal tumors.nnnMATERIALS AND METHODSnPatients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) (2005-2012) for localized renal cell carcinoma were analyzed. Multivariate logistic regressions were used to test the association between high-risk status and postoperative complications adjusting for patient, tumor, and operative characteristics.nnnRESULTSnOf 1092 patients undergoing PN (71.9%) or RN (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as high risk, and 175 patients (16%) developed at least 1 complication (mean 1.6 ± 1.0). Of note, 22.4% and 14.1% of high- and low-risk patients developed a complication, respectively (P = .002). Comparing high- and low-risk patients, significant differences in Clavien I-II (20.4% vs 11.1%; P <.001) and medical (16.1% vs 8.1%, P <.001) complications were observed, whereas no differences were seen in Clavien III-V or surgical complications. No differences in complications were observed comparing patients treated with RN and PN, albeit high-risk patients were more likely to undergo RN (35.3% vs 25.9%, P = .04). After adjustment, the odds of incurring any complication were 1.9 times higher in high- compared with low-risk patients (odds ratio 1.9 [confidence interval 1.3-2.8]).nnnCONCLUSIONnRegardless of surgical type, patients deemed high risk by age and comorbidity criteria were more likely to incur a postoperative complication after renal mass resection. Improved understanding of surgical risks in the elderly and infirmed will help better inform patients deciding between active surveillance and resection of renal tumors.

Piperlongumine promotes autophagy via inhibition of Akt/mTOR signalling and mediates cancer cell death

Background:The Akt/mammalian target of rapamycin (mTOR) signalling pathway serves as a critical regulator of cellular growth, proliferation and survival. Akt aberrant activation has been implicated in carcinogenesis and anticancer therapy resistance. Piperlongumine (PL), a natural alkaloid present in the fruit of the Long pepper, is known to exhibit notable anticancer effects. Here we investigate the impact of PL on Akt/mTOR signalling.Methods:We examined Akt/mTOR signalling in cancer cells of various origins including prostate, kidney and breast after PL treatment. Furthermore, cell viability after concomitant treatment with PL and the autophagy inhibitor, Chloroquine (CQ) was assessed. We then examined the efficacy of in vivo combination treatment using a mouse xenograft tumour model.Results:We demonstrate for the first time that PL effectively inhibits phosphorylation of Akt target proteins in all tested cells. Furthermore, the downregulation of Akt downstream signalling resulted in decrease of mTORC1 activity and autophagy stimulation. Using the autophagy inhibitor, CQ, the level of PL-induced cellular death was significantly increased. Moreover, concomitant treatment with PL and CQ demonstrated notable antitumour effect in a xenograft mouse model.Conclusions:Our data provide novel therapeutic opportunities to mediate cancer cellular death using PL. As such, PL may afford a novel paradigm for both prevention and treatment of malignancy.

A Review of Contemporary Data on Surgically Resected Renal Masses—Benign or Malignant?

OBJECTIVEnTo clearly define the proportions of benign vs malignant histologic findings in resected renal masses through an in-depth review of the contemporary medical data to assist in preoperative risk assessment.nnnMATERIALS AND METHODSnPubMed and select oncology congresses were searched for publications that identify the histologic classification of resected renal masses in a representative sample from the contemporary data: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit 2003-2011.nnnRESULTSnWe identified 26 representative studies meeting the inclusion criteria and incorporating 27,272 patients. The frequency of benign tumors ranged from 7% to 33%, with most studies within a few percentage points of the mean (14.5% ± 5.2%, median 13.9%). Clear cell renal cell carcinoma occurred in 46% to 83% of patients, with a mean of 68.3% (median 61.3; SDxa0= 11.9%). An inverse relationship between tumor size and benign pathologic features was identified in 14 of 19 (74%) studies that examined an association between tumor size and pathologic characteristics. A statistically significant correlation between clear cell renal cell carcinoma and tumor size was identified in 13 of 19 studies (63%). The accuracy of preoperative cross-sectional imaging was low in the 2 studies examining computed tomography (17%).nnnCONCLUSIONnBenign renal tumors represent ∼15% of detected surgically resected renal masses and are more prevalent among small clinical T1a lesions. Noninvasive preoperative differentiation between more and less aggressive renal masses would be an important clinical advance that could allow clinicians greater diagnostic confidence and guide patient management through improved risk stratification.

Coexisting Hybrid Malignancy in a Solitary Sporadic Solid Benign Renal Mass: Implications for Treating Patients Following Renal Biopsy

PURPOSEnConcern regarding coexisting malignant pathology in benign renal tumors deters renal biopsy and questions its validity. We examined the rates of coexisting malignant and high grade pathology in resected benign solid solitary renal tumors.nnnMATERIALS AND METHODSnUsing our prospectively maintained database we identified 1,829 patients with a solitary solid renal tumor who underwent surgical resection between 1994 and 2012. Lesions containing elements of renal oncocytoma, angiomyolipoma or another benign pathology formed the basis for this analysis. Patients with an oncocytic malignancy without classic oncocytoma and those with known hereditary syndromes were excluded from study.nnnRESULTSnWe identified 147 patients with pathologically proven elements of renal oncocytoma (96), angiomyolipoma (44) or another solid benign pathology (7). Median tumor size was 3.0 cm (IQR 2.2-4.5). As quantified by the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score, tumor anatomical complexity was low in 28% of cases, moderate in 56% and high in 16%. Only 4 patients (2.7%) were documented as having hybrid malignant pathology, all involving chromophobe renal cell carcinoma in the setting of renal oncocytoma. At a median followup of 44 months (IQR 33-55) no patient with a hybrid tumor experienced regional or metastatic progression.nnnCONCLUSIONSnIn our cohort of patients with a solitary, sporadic, solid benign renal mass fewer than 3% of tumors showed coexisting hybrid malignancy. Importantly, no patient harbored coexisting high grade pathology. These data suggest that uncertainty regarding hybrid malignant pathology coexisting with benign pathological components should not deter renal biopsy, especially in the elderly and comorbid populations.

Familiarity and self-reported compliance with American Urological Association best practice recommendations for use of thromboembolic prophylaxis among American Urological Association members.

PURPOSEnThromboprophylaxis with subcutaneous heparin or low molecular weight heparin is now an integral part of national surgical quality and safety assessment efforts, and has been incorporated into the current AUA Best Practice Statement. We evaluated familiarity and compliance with the AUA Best Practice Statement, assessed practice patterns in terms of perioperative thromboprophylaxis and specifically examined self-reported compliance in high risk patients undergoing radical cystectomy.nnnMATERIALS AND METHODSnAn electronic survey was sent to AUA members with valid e-mail addresses (10,966). Associations between AUA Best Practice Statement adherence and factors such as urological specialty, graduation year and guideline familiarity were assessed using chi-square analyses and generalized estimating equations.nnnRESULTSnWith 1,210 survey responses the largest group of respondents was urological oncologists and/or laparoscopic/robotic specialists (26.0%). This group was more likely to use thromboprophylaxis than nonurological oncologists and/or laparoscopic/robotic specialists in high risk patients (OR 1.3, CI 1.1-1.5). Respondents aware of the AUA Best Practice Statement guidelines (50.7%) were more likely to use thromboprophylaxis (OR 1.4, CI 1.2-1.6). Although 18.1% of urological oncologists and/or laparoscopic/robotic specialists and 34.2% of nonurological oncologists and/or laparoscopic/robotic specialists avoided routine thromboprophylaxis in patients undergoing radical cystectomy, the former were more likely to use thromboprophylaxis (p <0.0001) than other respondents. Urologists graduating after the year 2000 used thromboprophylaxis in high risk patients undergoing radical cystectomy more often than did earlier graduates (79.2% vs 63.4%, p <0.0001).nnnCONCLUSIONSnAlthough younger age and self-reported urological oncologist and/or laparoscopic/robotic specialist status correlated strongly with thromboprophylaxis use, self-reported adherence to AUA Best Practice Statement was low, even in high risk cases with clear AUA Best Practice Statement recommendations such as radical cystectomy. These data identify opportunities for quality improvement in patients undergoing major urological surgery.

Residual Parenchymal Volume, Not Warm Ischemia Time, Predicts Ultimate Renal Functional Outcomes in Patients Undergoing Partial Nephrectomy

OBJECTIVEnTo examine relative contributions of functional parenchymal preservation and renal ischemia following nephron-sparing surgery (NSS). While residual functional parenchymal volume (FPV) is proposed as the key factor in predicting functional outcomes following NSS, efforts to curtail ischemia time continue to add technical complexity to partial nephrectomy.nnnMETHODSnOur kidney cancer database was queried for patients who underwent NSS with warm ischemia time (WIT). Patients with cross-sectional imaging for FPV calculation were included. Cylindrical volume approximation methodology was used to calculate FPV, accounting for the volume of tumors endophytic component. Percent estimated glomerular filtration rate (eGFR) preservation, perioperatively and at 6xa0months, was the outcome metric. Spearman correlation and linear regression analyses were used to evaluate associations of WIT and %FPV preservation with renal function preservation.nnnRESULTSnOf the 179 patients included, median preoperative eGFR was 88.4 (9.5% chronic kidney disease III or IV), tumor size was 2.7xa0cm (interquartile range [IQR] 2.0-3.6xa0cm), and R.E.N.A.L. nephrometry was low in 34%, intermediate in 57%, and high in 9%. Median WIT was 30xa0minutes (IQR 24-36), resulting in 97.4% FPV preservation. Median postoperative eGFR at 6.4xa0months was 80.5 (19.1% chronic kidney disease III or IV), a median of 93.1% eGFR preservation (IQR 85.1-101.7). At discharge, WIT (Pxa0<.001), not %FPV (Pxa0= .112), was associated with %eGFR preservation. However, 6xa0months following surgery, on multivariable analysis, both preoperative eGFR (linear regression coefficientxa0=xa0-0.208, Pxa0= .006) and %FPV preservation (linear regression coefficientxa0= 0.491, Pxa0= .001), but not WIT (Pxa0= .946), demonstrated statistically significant association with %eGFR preservation.nnnCONCLUSIONnResidual FPV, and not WIT, appears to be the main predictor of ultimate renal function following NSS.

Care Transitions between Hospitals are Associated with Treatment Delay for Patients with Muscle Invasive Bladder Cancer

PURPOSEnHypothesizing that changing hospitals between diagnosis and definitive therapy (care transition) may delay timely treatment, we identified the association between care transitions and a treatment delay of 3 months or greater in patients with muscle invasive bladder cancer.nnnMATERIALS AND METHODSnUsing the National Cancer Database we identified all patients with stage II or greater urothelial carcinoma treated from 2003 to 2010. Care transition was defined as a change in hospital from diagnosis to definitive treatment course, that is diagnosis to radical cystectomy or the start of neoadjuvant chemotherapy. Logistic regression models were used to test the association between care transition and treatment delay.nnnRESULTSnOf 22,251 patients 14.2% experienced a treatment delay of 3 months or greater and this proportion increased with time (13.5% in 2003 to 2006 vs 14.8% in 2007 to 2010, p = 0.01). Of patients who underwent a care transition 19.4% experienced a delay to definitive treatment compared to 10.7% diagnosed and treated at the same hospital (p <0.001). The proportion of patients with a care transition increased during the study period (37.4% in 2003 to 2006 vs 42.3% in 2007 to 2010, p <0.001). After adjustment patients were more likely to experience a treatment delay when undergoing a care transition (OR 2.0, 95% CI 1.8-2.2).nnnCONCLUSIONSnPatients with muscle invasive bladder cancer who underwent a care transition were more likely to experience a treatment delay of 3 months or greater. Strategies to expedite care transitions at the time of hospital referral may improve quality of care.

Lymphopenia is an independent predictor of inferior outcome in papillary renal cell carcinoma

PURPOSEnLymphopenia as a likely index of poor systemic immunity is an independent predictor of inferior outcome in patients with clear cell renal cell carcinoma (RCC). We sought to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in a cohort of patients with papillary RCC (PRCC).nnnMATERIALS AND METHODSnA prospectively maintained, renal cancer database was analyzed. Patients with preoperative ALC, within 3 months before surgery, were eligible for the study. Those with multifocal or bilateral renal tumors were excluded. Correlations between ALC and age, gender, smoking, Charlson comorbidity index, pathologic T category, PRCC subtype, and TNM stage were evaluated. Differences in overall survival (OS) and cancer-specific survival by ALC status were assessed using the log-rank test and cumulative incident estimators, respectively. Cox proportional hazards model was used for multivariable analyses.nnnRESULTSnA total of 192 patients met the inclusion criteria. As a continuous variable, preoperative ALC was associated with higher TNM stage (P = 0.001) and older age (P = 0.01). As a dichotomous variable, lymphopenia (<1,300 cells/µl) was associated with higher TNM stage (P = 0.003). On multivariable analyses, controlling for covariates, after a median follow-up of 37.3 months, lymphopenia was associated with inferior OS (hazard ratio = 2.3 [95% CI: 1.2-4.3], P = 0.011) and trended to significance for cancer-specific survival (P = 0.071). Among patients with nonmetastatic disease and lymphopenia, OS at 37.5 months was shorter compared with those with normal ALC (83% vs. 93%, P = 0.0006).nnnCONCLUSIONSnIn patients with PRCC, lymphopenia is associated with lower survival independent of TNM stage, age, and histology. ALC may provide an additional preoperative prognostic factor.

Variation in performance of candidate surgical quality measures for muscle-invasive bladder cancer by hospital type

To test the association between hospital type and performance of candidate quality measures for treatment of muscle‐invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion.

Comparison of prostate cancer diagnosis in patients receiving unrelated urological and non-urological cancer care.

To evaluate prostate cancer diagnosis rates and survival outcomes in patients receiving unrelated (non‐prostate) urological care with those in patients receiving non‐urological care.