Timothy Ito

Anatomic Complexity Quantitated by Nephrometry Score Is Associated With Prolonged Warm Ischemia Time During Robotic Partial Nephrectomy

OBJECTIVEnTo assess the association between nephrometry score (NS) and prolonged warm ischemia time (WIT) in patients undergoing robotic partial nephrectomy (RPN) for clinically localized renal masses.nnnMETHODSnWe queried our prospectively maintained kidney cancer database to identify all patients undergoing RPN for localized tumors from 2007-2012. Patient and tumor characteristics were compared between complexity groups using analysis of variance and chi square tests. Multivariate logistic regression models were used to examine the relationship between NS complexity and warm ischemia >30xa0minutes.nnnRESULTSnThree hundred seventy-five patients (mean age, 59 ± 11xa0years; mean Charlson comorbidity index, 1.0 ± 1.3) undergoing RPN under warm ischemia for clinically localized renal tumors (mean tumor size, 3.1 ± 1.5xa0cm; mean NS, 6.8 ± 1.8) met inclusion criteria and had NS available. Stratified by complexity, groups differed with respect to age at surgery, tumor size, proximity to the hilum, collecting system entry, estimated blood loss, and operative time (all Pxa0valuesxa0≤.05). Significant differences in mean WIT were observed when comparing low (19.4 ± 12.1xa0minutes), intermediate (28.6 ± 12.8xa0minutes), and high (36.1 ± 13.7xa0minutes) NS complexity groups (Pxa0<.0001). Adjusting for confounders, patients with intermediate (odds ratio, 2.1; confidence interval, 1.2-3.9) and high (odds ratio, 3.7; confidence interval, 1.1-11.8) NS complexity were more likely to require prolonged WIT when compared with patients with low complexity tumors.nnnCONCLUSIONnIn our large institutional cohort, quantification of anatomic complexity using the NS is associated with WIT >30xa0minutes in patients undergoing RPN for localized renal tumors. This provides further evidence that standardized reporting of tumor anatomic complexity affords meaningful outcome comparisons.

Is anatomic complexity associated with renal tumor growth kinetics under active surveillance

INTRODUCTIONnLinear growth rate (LGR) is the most commonly employed trigger for definitive intervention in patients with renal masses managed with an initial period of active surveillance (AS). Using our institutional cohort, we explored the association between tumor anatomic complexity at presentation and LGR in patients managed with AS.nnnMETHODS AND MATERIALSnEnhancing renal masses managed expectantly for at least 6 months were included for analysis. The association between Nephrometry Score and LGR was assessed using generalized estimating equations, adjusting for the age, Charlson score, race, sex, and initial tumor size.nnnRESULTSnOverall, 346 patients (401 masses) met the inclusion criteria (18% ≥ cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44% patients showed progression to definitive intervention with a median duration of 27 months (range: 6-130). On comparing patients managed expectantly to those requiring intervention, no difference was seen in median tumor size at presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74 vs. 65 y, P < 0.001), Charlson comorbidity score (3 vs. 2, P<0.001), and average LGR (0.23 vs. 0.49 cm/y, P < 0.001) were observed between groups. Following adjustment, for each 1-point increase in Nephrometry Score sum, the average tumor LGR increased by 0.037 cm/y (P = 0.002). Of the entire cohort, 6 patients (1.7%) showed progression to metastatic disease.nnnCONCLUSIONSnThe demonstrated association between anatomic tumor complexity at presentation and renal masses of LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor individual patient radiographic surveillance schedules and warrants further evaluation.

Surgical Apgar Score Predicts an Increased Risk of Major Complications and Death after Renal Mass Excision

PURPOSEnTailoring perioperative management to minimize the postoperative complication rates depends on reliable prognostication of patients most at risk. The Surgical Apgar Score is an objective measure of the operative course validated to predict major complications and death after general/vascular surgery. We assessed the ability of the Surgical Apgar Score to identify patients most at risk for postoperative morbidity and mortality after renal mass excision.nnnMATERIALS AND METHODSnData for 886 patients undergoing renal mass excision via radical or partial nephrectomy from 2010 to 2013 were extracted from a prospectively collected database. The Surgical Apgar Score was calculated using electronic anesthesia records. Major postoperative complications, readmission and reoperation within 30 days of surgery as well as 90-day mortality were examined.nnnRESULTSnOverall 13.2% of patients experienced major postoperative complications at 30 days. Clavien grade I, II, III, IV and V complications were experienced by 1.7%, 2.9%, 5.8%, 1.9% and 0.9%, respectively. The 90-day all cause mortality rate was 1.4%. The Surgical Apgar Score was significantly lower in patients experiencing major complications (mean 7.3 vs 7.8, p=0.004) and death (6.3 vs 7.7, p=0.03). Patients with a Surgical Apgar Score of 4 or less were 3.7 times more likely to experience a major complication (p=0.01) and 24 times more likely to die within 90 days of surgery (p=0.0007) compared to patients with a Surgical Apgar Score greater than 8.nnnCONCLUSIONSnThe Surgical Apgar Score is an easily collected metric that can identify patients at higher risk for major complications and death after renal mass excision. A prospective trial to help further delineate the optimal use of this tool in an adjusted perioperative management approach with patients undergoing renal mass excision is warranted.

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.

Patients with anatomically “simple” renal masses are more likely to be placed on active surveillance than those with anatomically “complex” lesions

OBJECTIVEnTo determine if radiographically less complex renal lesions are deemed clinically less worrisome and therefore are more likely to be considered for active surveillance (AS).nnnMETHODSnWe examined our prospective institutional database to identify and compare patients with localized renal cell carcinoma undergoing an initial period of AS or immediate surgery. Multivariate logistic regression was used to examine covariates associated with receipt of AS.nnnRESULTSnOf 1,059 patients with available anatomic complexity data, 195 underwent an initial period of AS (median duration of AS 25.6 mo [interquartile range: 11.8-52.8 mo]). Compared with patients undergoing immediate surgical treatment, patients selected for AS had lower overall nephrometry scores (NS) with tumors that were smaller, further from the sinus or urothelium, more often polar, and less often hilar (P<0.0015 all comparisons). After adjustment for age, largest tumor size, individual components of NS, total NS, and Charlson comorbidity index, total NS (odds ratio [OR] = 1.9 [CI: 1.4-2.5]), R score of 1 (OR = 5.2 [CI: 1.8-15.2]), N score of 1 (OR = 2.3 [CI: 1.5-3.6]), L score of 1 (OR = 1.4 [CI: 0.84-2.2]), and nonhilar tumor location (OR = 2.7 [CI: 1.2-5.8]) increased the probability of being selected for AS compared with immediate surgery. Findings remained significant in a subanalysis of T1a renal masses.nnnCONCLUSIONSnLower tumor anatomic complexity was strongly associated with the decision to proceed with AS in patients with stage I renal mass. Not only may these data afford new insights into renal mass treatment trends, but the findings may also prove useful in the development of objective protocols to most appropriately select patients for AS.

Genomic Copy Number Alterations in Renal Cell Carcinoma with Sarcomatoid Features

PURPOSEnSarcomatoid changes in renal cell carcinoma are associated with a poorxa0prognosis. The identification of genetic alterations that drive this aggressivexa0phenotype could aid in the development of more effective targeted therapies.xa0In this study we aimed to pinpoint unique copy number alterations in sarcomatoid renal cell carcinoma compared to classical renal cell carcinoma subtypes.nnnMATERIALS AND METHODSnGenomic copy number analysis was performed using single nucleotide polymorphism based microarrays on tissue extracted from the tumors of 81 patients who underwent renal mass excision, including 17 with sarcomatoid renal cell carcinoma.nnnRESULTSnSarcomatoid renal cell carcinoma showed a significantly higher number of copy number alterations than clear cell, papillary and chromophobe renal cell carcinoma (mean 18.0 vs 5.8, 6.5 and 7.2, respectively, p <0.0001). Copy number losses of chromosome arms 9q, 15q, 18p/q and 22q, and gains of 1q and 8q occurred in a significantly higher proportion of sarcomatoid renal cell carcinomas than in the other 3 histologies. Patients with sarcomatoid renal cell carcinoma demonstrated significantly worse overall survival compared to those without that condition on Kaplan-Meier analysis (p = 0.0001). Patients with 9 or more copy number alterations also demonstrated significantly worse overall survival than those with fewer than 9 copy number alterations (p = 0.004).nnnCONCLUSIONSnSarcomatoid changes in renal cell carcinoma are associated with axa0high rate of chromosomal imbalances with losses of 9q, 15q, 18p/q and 22q, andxa0gains of 1q and 8q occurring at significantly higher frequencies in comparison to nonsarcomatoid renal cell carcinoma. Identifying candidate driver genes or tumor suppressor loci in these chromosomal regions may help identify targets for future therapies.

Is extended pharmacologic venous thromboembolism prophylaxis uniformly safe after radical cystectomy

OBJECTIVEnTo quantitate the risk of clinically significant renal function deterioration after radical cystectomy (RC), which could result in supratherapeutic levels of low-molecular-weight heparin (LMWH) and increased risk of bleeding events with the use of extended pharmacologic venous thromboembolism prophylaxis (EPVTEP) after hospital discharge.nnnMETHODSnPatients undergoing RC between 2006 and 2011 were identified from the institutional registry. Estimated glomerular filtration rate (eGFR) was calculated and categorized as preoperative, discharge, and nadir. Perioperative eGFR trends in patients who would have been candidates for EPVTEP were evaluated.nnnRESULTSnThree hundred four patients with eGFR >30 mL/min/1.73 m(2) at the time of hospital discharge were included in the analysis as potentially eligible for EPVTEP. Large portion of patients (43%) exhibited decline in eGFR after discharge. Importantly, 13.0% of patients (n = 40), who would have qualified for EPVTEP at discharge, experienced nadir GFR below the 30-mL/min/1.73 m(2) threshold value at which LMWH would have become supratherapeutic. The odds ratio for developing a GFR <30 mL/min/1.73 m(2) was 9.1 (95% confidence interval, 4.3-19.3; P <.001), comparing those with a discharge GFR ≥60 mL/min/1.73 m(2) with those with a discharge GFR <60 mL/min/1.73 m(2).nnnCONCLUSIONnMore than 10% experienced an eGFR, which would have rendered LMWH supratherapeutic and potentially would have placed the patient at risk for clinically significant bleeding. Although postoperative venous thromboembolic event after RC is a recognized concern, a better understanding of the risks of EPVTEP is needed before this strategy is universally adopted in patients undergoing RC.

Perioperative Outcomes Following Partial Nephrectomy Performed on Patients Remaining on Antiplatelet Therapy

Purpose: We evaluated the risk of bleeding complications in patients undergoing partial nephrectomy in whom perioperative antiplatelet therapy was continued, as antiplatelet therapy is increasingly used and hemorrhage is a significant concern in partial nephrectomy. Materials and Methods: In this 2‐center retrospective analysis 1,097 patients underwent partial nephrectomy between 2000 and 2014. The cohort was split into 3 groups of perioperative continuation of antiplatelet therapy (group 1—67), antiplatelet therapy stopped preoperatively (group 2—254) and no chronic antiplatelet therapy (group 3—776). Bleeding complications were defined as any transfusion, or any hospital readmission or secondary procedure performed for hemorrhage. Multivariable analysis was performed to elucidate independent risk factors for bleeding complications. Results: Patients in group 1 were older (median age 66 years vs 64 and 57 years in groups 2/3, p <0.0001), and had greater comorbidity (median ASA classification score 3 vs 2 and 2, p <0.0001). Group 1 had a higher rate of bleeding complications (20.9% vs 7.1% and 6.4%, p <0.0001) and transfusions (16.4% vs 5.9% and 5.4%, p=0.002). Multivariable analysis revealed continued antiplatelet therapy was an independent predictor of bleeding complications (OR 2.19, 95% CI 1.06–4.51, p=0.03). These findings appear attributable to intraoperative clopidogrel use. On multivariable analysis the use of aspirin alone was not associated with bleeding complications (OR 1.64, 95% CI 0.72–3.75, p=0.24). Conclusions: The risk of bleeding complications due to antiplatelet therapy use at partial nephrectomy may be due to clopidogrel. The need to continue perioperative aspirin alone does not appear to be a contraindication to the safe performance of partial nephrectomy.

Chapter 6 – High Grade Prostatic Intraepithelial Neoplasia and Atypical Glands

Abstract Historically, high-grade prostatic intraepithelial neoplasia (HGPIN) has been considered a premalignant lesion characterized by atypical proliferation and nuclear features in the setting of benign appearing acini and ducts. Rates of concurrent cancer after initial sextant biopsy diagnosis of HGPIN in the past were much higher due to undersampling, resulting in increased rates of cancer detection with immediate repeat biopsy. Currently, improved identification of smaller foci of cancer with initial extended core prostate biopsy has obviated the need for repeat biopsy in most patients diagnosed with HGPIN, given a similar cancer detection rate to those with a completely benign baseline biopsy. The exception is the subset of patients found to have multifocal HGPIN who continue to be at increased risk for subsequent cancer detection. In contrast, atypical small acinar proliferation (ASAP) is a diagnostic category signaling the presence of pathologic features suspicious but not definitive for malignancy. The most common cause for this diagnostic ambiguity is small size of the foci of atypical glands. Frequently, this diagnosis represents undersampling of concurrent adenocarcinoma, thus the rate of subsequent cancer diagnosis is high, ranging from 27% to 71%. As a result, expert consensus suggests that patients with this finding on initial biopsy should be followed closely and undergo at least one short interval repeat biopsy for risk restratification.

Kidney cancer in 2014

Kidney cancer research in 2014 was characterized by a diverse array of studies. Advances were made in both the localized and the metastatic renal cell carcinoma (RCC) arenas. Importantly, significant progress was also made in our understanding of the underpinnings of RCC tumorigenesis and progression.