Faculty Bibliography

PURPOSE: We analyze the relationship among various patient, operative and tumor characteristics to determine which factors correlate with renal parenchymal volume loss after nephron sparing surgery using a novel 3-dimensional volume assessment. MATERIALS AND METHODS: We conducted a retrospective review of an institutional database of patients who underwent nephron sparing surgery from 1992 to 2014 for a localized renal mass. Tumors were classified according to the R.E.N.A.L. nephrometry system. Using 3-dimensional reconstruction imaging software, preoperative and postoperative renal parenchymal volume was calculated for the ipsilateral and contralateral kidney. RESULTS: A total of 158 patients were analyzed. Mean patient age was 58.7 years and mean followup was 40.1 months. Mean preoperative tumor volume was 34.0 cc and mean tumor dimension was 3.4 cm. Mean R.E.N.A.L. nephrometry score was 6.2, with 60.1%, 34.2% and 5.7% of tumors classified as low, medium and high complexity, respectively. Mean change in renal parenchymal volume after nephron sparing surgery was -15.3% for the ipsilateral kidney and -6.8% for total kidney volume. On univariate analysis ischemia time, tumor size, R.E.N.A.L. nephrometry score, complexity grouping and the individual nephrometry components of tumor size, percent exophytic, anterior/posterior, depth and tumor proximity to the renal artery or vein were associated with greater renal parenchymal volume loss. On multivariate analysis only ischemia time, tumor size, posterior location and percent exophytic were independently associated with more renal parenchymal volume loss. CONCLUSIONS: Using precise 3-dimensional volumetric analysis we found that ischemia time, tumor size and endophytic/exophytic properties of a localized renal mass are the most important determinants of renal parenchymal volume loss.

BACKGROUND:Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria. QUESTIONS/PURPOSES/OBJECTIVE:We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate. METHODS:In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation. RESULTS:IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation. In vitro immunomodulatory activity of IDR-1018 included inducing production of MCP-1 in the absence of other inflammatory stimuli and to potently blunt excess production of proinflammatory cytokines and MCP-1 induced by lipopolysaccharide. Higher concentrations of IDR-1018 were required to blunt production of proinflammatory cytokines and MCP-1 in the presence S aureus. The largest in vivo immunomodulatory effect of IDR-1018 was to reduce tumor necrosis factor-α levels induced by S aureus by 60% (p = 0.006). Most importantly, IDR-1018 reduced S aureus-induced failures of osseointegration by threefold (p = 0.022) and increased osseointegration as measured by ultimate force (5.4-fold, p = 0.033) and average stiffness (4.3-fold, p = 0.049). CONCLUSIONS:IDR-1018 is potentially useful to reduce orthopaedic infections by directly killing bacteria and by recruiting macrophages to the infection site. CLINICAL RELEVANCE/CONCLUSIONS:These findings make IDR-1018 an attractive candidate to explore in larger animal models to ascertain whether its effects in our in vitro and mouse experiments can be replicated in more clinically relevant settings.

OBJECTIVE: To compare the utilization, perioperative complications and predictors of LCA versus RPN in the treatment of localized renal tumors. METHODS: From the Nationwide Inpatient Sample we identified patients undergoing RPN or LCA for the treatment of localized renal tumors from October 2008 through 2010. Patient and hospital-specific factors which predict postoperative complications and use of LCA were investigated. RESULTS: 14,275 patients with localized renal tumors were identified: 70.3% had RPN and 29.7% had LCA. LCA was more common in older patient and at hospitals without robotic consoles. No difference was identified in perioperative complications (0.2% vs. 0.2%), transfusion (5.1% vs. 6.2%), length of stay (2.9 vs. 3.0 days) or median cost ($41,753 vs. $44,618) between the groups, LCA vs. RPN. On multivariate analysis sicker patients were more likely to have LCA (OR 1.34, p=0.048) and sicker patients had greater postoperative complications (OR 3.30, p<0.001); LCA did not predict more complications (OR 1.63, p=0.138) and LCA was performed at hospitals without RCs (OR 0.02, p<0.001). Limitations include observational study design, inability to assess disease severity, operative time, or body mass index, which may affect patient selection and outcomes. CONCLUSIONS: More patients had RPN vs. LCA; surgical technique was not predictive of postoperative complications. As technology develops to treat localized renal tumors, it will be important to continue to track outcomes and costs for procedures including RPN and LCA.

INTRODUCTION AND OBJECTIVES: Radical prostatectomy (RP) is associated with a high risk of intraoperative blood loss and subsequent blood transfusions. The shift in surgical technique from open radical prostatectomy (ORP) to robot-assisted radical prostatectomy (RARP) has resulted in lower operative blood loss, and reduced the need for transfusions. We analyzed the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database to compare real-world, contemporary trends in utilization and timing of blood transfusion following ORP and RARP. METHODS: We identified men undergoing both RARP and ORP and then queried for patients who received a blood transfusion in the perioperative period. The outcomes of interest were need and timing of perioperative blood transfusion (PBT), which was categorized into early (postoperative day [POD] /=2). Logistic regression analysis was used to identify variables associated with the need and timing for PBT. RESULTS: A total of 16,144 men who underwent RP were identified from 2007 to 2012. The overall PBT rate was 3.1%. Highest rate of transfusions occurred on day of surgery for patients undergoing ORP, and first POD for patients undergoing RARP. On multivariate analysis significant predictors of blood transfusion included history of bleeding disorder (OR: 2.8, p=0.002), preoperative dyspnea (odds ratio [OR]: 1.7, p=0.03), starting hematocrit <42% (OR: 1.9, p<0.001), open approach (OR: 0.09, p<0.001), year of surgery (OR: 0.5, p<0.001), resident involvement (OR: 1.6, p=0.003), and operative time (OR: 4.4, p<0.001). The only predictor of receiving a blood transfusion on POD 2 or later was having the procedure performed through a robot-assisted approach (OR: 3.7, p<0.001). CONCLUSIONS: In this study we found that the rate of perioperative transfusions is lower than previously published. A clear separation in timing of transfusion exists based on the utilized surgical approach. It is prudent that surgeons performing RARP be aware of the low, but present risk of a delayed blood transfusion.

PURPOSE: End-stage renal disease (ESRD) and acquired renal cystic disease associated with dialysis are known risk factors of papillary renal cell carcinoma (pRCC); however, it is not known whether renal insufficiency alone is a risk factor for pRCC. Our aim was to test whether renal insufficiency is associated with an increased preponderance of pRCC. METHODS: Retrospective review of institutional database to identify all patients who underwent extirpative renal surgery for renal cell carcinoma (RCC) with complete records from 1992 to 2012. We excluded those patients with preoperative ESRD as defined by GFR < 15 mL/min/1.73 m(2). The dependent variable was histologic RCC subtype. Independent variables included demographic data, comorbidities, and renal functional data. Multivariate analysis by binary logistic regression was used to determine factors that independently were associated with pRCC development. RESULTS: A total of 1,226 patients met inclusion criteria, of which 15 % were pRCC. There was a positive association between likelihood of pRCC histology of RCC and increasing preoperative chronic kidney disease (CKD) stage (p = 0.021). Multivariate regression analysis indicated that male gender, race, and declining renal function categorized both by GFR and CKD stage were independently associated with a higher likelihood of pRCC histology as compared to other RCC histology. CONCLUSIONS: Within a large cohort of patients with a diagnosis of RCC, declining renal function was independently associated with an increased likelihood of pRCC histology. This finding and the available molecular evidence indicating protein expression similarity between pRCC and resident stem cells, which appear to be upregulated with kidney damage, suggest a possible causal relationship between renal injury and pRCC.

OBJECTIVE: To investigate the incidence and timing of venous thromboembolism (VTE) and identify risk factors for venous thromboembolism among patients undergoing major surgery for urologic malignancies. VTE events are stratified by occurrence in the inpatient vs outpatient settings. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Statistical Classification of Diseases, Ninth Revision codes to identify patients undergoing major surgery for urologic malignancies between 2005 and 2012. The incidence of overall 30-day VTE, postdischarge VTE, and post-VTE death was calculated for each surgical procedure. Logistic regression analysis was used to identify risk factors for VTE, adjusting for covariates including age, race, gender, smoking status, medical comorbidities, performance of pelvic lymph node dissection, and operative time. RESULTS: The study identified 27,455 patients who underwent an operation for malignancy--radical nephrectomy, partial nephrectomy, nephroureterectomy, radical prostatectomy, or radical cystectomy. The incidence and timing of VTE varied substantially across the procedures of interest. Overall, VTE occurred after radical cystectomy in 113 of 2065 of patients (5.5%), whereas only 19 of 2624 (0.7%) and 12 of 1690, respectively, of patients undergoing minimally invasive radical or partial nephrectomy procedures suffered a VTE event within 30-days of surgery. Among patients suffering a VTE after radical prostatectomy, 147 of 178 of venous thromboembolic events (82.6%) occurred after hospital discharge. CONCLUSION: This study demonstrates the significant burden of VTE beyond the time of hospital discharge. Identification of high-risk patients should prompt consideration of extended-duration VTE prophylaxis in the outpatient setting.

OBJECTIVE: To analyze the influence of preoperative renal function on postoperative renal outcomes after radical nephrectomy (RN) and nephron-sparing surgery (NSS) for malignancy in patients stratified according to preoperative chronic kidney disease (CKD) stage and surgical extent (NSS vs RN). PATIENTS AND METHODS: Retrospective review of patients undergoing renal surgery for localized renal masses stratified by surgical extent and preoperative CKD stage based on glomerular filtration rate (GFR) level: stage I (>90 mL/min/1.73 m(2)), stage II (60-89 mL/min/1.73 m(2)), and stage III (30-59 mL/min/1.73 m(2)). Survival analysis for significant renal impairment was based on freedom from the development of new-onset GFR <30 or <45 mL/min/1.73 m(2). RESULTS: A total of 1306 patients were included in the analysis with preoperative CKD stage I (27.9%), II (52.1%), and III (20.1%); 41.3% and 58.7% underwent NSS and RN, respectively. NSS was associated with a lower annual rate of GFR decline in preoperative CKD stage-I (P = .028) and stage-II patients (P = .018), but not in CKD stage-III patients (P = .753). Overall, 5.0% and 15.0% developed new-onset GFR <30 mL/min/1.73 m(2) and <45 mL/min/1.73 m(2), respectively. There was no difference in the probability of developing significant renal impairment between NSS and RN in CKD stage-I or -III patients, whereas only in CKD stage-II patients was the surgical extent independently associated with development of significant renal impairment (RN: odds ratio, 9.0; P = .042 for GFR <30 mL/min/1.73 m(2) and odds ratio, 2.3; P = .003 for GFR <45 mL/min/1.73 m(2)). CONCLUSION: Compared with RN, NSS is associated with a lower rate of GFR decline for preoperative CKD stage-I and -II patients, but only CKD stage-II patients demonstrated a decreased risk of developing significant renal impairment.

OBJECTIVE: To determine whether socioeconomic status (SES) predicts the size and local extent of tumors at presentation, and if this association leads to differences in survival. MATERIALS AND METHODS: The National Cancer Institute's Survival, Epidemiology, and End Results registry was queried for patients diagnosed with renal cancers between 2004 and 2010. Demographic, tumor, survival, and socioeconomic data were obtained. Cancers with T0 classification, nonrenal cell histology, or missing clinical or pathologic data were excluded. An SES measure was created from available metrics. Outcomes analyzed were tumor size, TNM classifications at diagnosis, tumor grade and histology subtype, and survival duration. RESULTS: A total of 40,212 cases were identified. On regression modeling, lower SES was an independent risk factor for tumor size >/= 4 cm (P = .003) and for T classification >/= T2 (P = .040) at presentation, but did not predict histology subtype, positive lymph nodes, or metastasis. Lower SES predicted high-grade disease on univariate analysis (P = .012) but lost significance in the multivariate model. Lower SES was also independently predictive of shortened cancer-specific survival on multivariate analysis after adjusting for available cofactors (lowest vs highest SES quartile; P = .001). CONCLUSION: This study suggests that low SES is correlated with poorer survival outcomes in renal cancer, and this may be related to a tendency toward larger and more locally advanced tumors at diagnosis. Additional investigation is needed to ascertain whether these effects could be mediated by relatively lower rates of incidental detection via abdominal imaging in disadvantaged populations.