Paul Russo

Publications (157)755.99 Total impact

• Article: Adverse Outcomes in Clear Cell Renal Cell Carcinoma with Mutations of 3p21 Epigenetic Regulators BAP1 and SETD2: a Report by MSKCC and the KIRC TCGA Research Network.

  A Ari Hakimi, Irina Ostrovnaya, Boris A Reva, Nikolaus Schultz, Ying-Bei Chen, Mithat Gonen, Han Liu, Shugaku Takeda, Martin H Voss, Satish K Tickoo, Victor E Reuter, Paul Russo, Emily H Cheng, Chris Sander, Robert J Motzer, James J-D Hsieh
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  ABSTRACT: Purpose To investigate the impact of newly identified chromosome 3p21 epigenetic tumor suppressors PBRM1, SETD2, and BAP1 on cancer specific survival (CSS) of 609 clear cell renal cell carcinoma (ccRCC) patients from two distinct cohorts. Patients and Methods Select sequencing on 3p tumor suppressors of 188 patients who underwent resection of primary ccRCC at the Memorial Sloan-Kettering Cancer Center (MSKCC) was performed to interrogate the genotype-phenotype associations. These findings were compared to analyses of the genomic and clinical dataset from our non-overlapping The Cancer Genome Atlas (TCGA) cohort of 421 primary ccRCC patients. Results 3p21 tumor suppressors are frequently mutated in both the MSKCC (PBRM1, 30.3%; SETD2, 7.4%; BAP1, 6.4%) and the TCGA (PBRM1, 33.5%; SETD2, 11.6%; BAP1, 9.7%) cohorts. BAP1 mutations are associated with worse CSS in both cohorts (MSKCC, p=0.002, HR 7.71 (2.08-28.6); TCGA, p=0.002, HR 2.21 (1.35-3.63)). SETD2 are associated with worse CSS in the TCGA cohort (p=0.036, HR 1.68 (1.04-2.73)). On the contrary, PBRM1 mutations, the second most common gene mutations of ccRCC, have no impact on CSS. Conclusion The chromosome 3p21 locus harbors three frequently mutated ccRCC tumor suppressor genes. BAP1 and SETD2 mutations (6-12%) are associated with worse CSS, suggesting their roles in disease progression. PBRM1 mutations (30-34%) do not impact CSS, implicating its principal role in the tumor initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic and molecular interrogation of this novel class of tumor suppressors.
  Clinical Cancer Research 04/2013; · 7.74 Impact Factor
• Article: Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors.

  Wenlei He, John C Cheville, Peter M Sadow, Anuradha Gopalan, Samson W Fine, Hikmat A Al-Ahmadie, Ying-Bei Chen, Esther Oliva, Paul Russo, Victor E Reuter, Satish K Tickoo
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  ABSTRACT: The 2004 World Health Organization classification of tumors defines epithelioid angiomyolipoma of kidney as a potentially malignant mesenchymal neoplasm with reported metastasis in approximately one-third of the cases. However, this conclusion was based primarily on individual case reports and small retrospective series. More recently reported larger series have shown varying results. We reviewed 437 consecutive renal angiomyolipomas with primary resection at three tertiary-care institutions with high nephrectomy volumes. Only tumors showing >80% epithelioid histology were included in this study. Tumors resected elsewhere and reviewed in consultation were not included. Twenty of these 437 (4.6%) were classified as epithelioid angiomyolipoma. The female to male ratio was 11:9, mean age 49.7 (range, 30-80) years, and mean tumor size 8.7 (range, 1-25) cm. Microscopic tumor necrosis was present in 10 (50%) tumors and mitotic activity (range, <1-5/10 high power fields) in 8 (40%); atypical mitoses were seen in only 1 (5%) tumor. Pleomorphic ganglion-like or multinucleated giant cells were seen in 18 (90%) tumors. With a mean follow-up of 82.5 (range, 1-356) months, seventeen patients were alive with no-evidence-of-disease at the time of last follow-up; two patients died of unrelated causes with no-evidence-of-disease, and one patient (5%) developed distant metastases. Our data, based on consecutively resected angiomyolipomas with long clinical follow-up, suggests that epithelioid angiomyolipomas constitute a small proportion of all angiomyolipomas, and the rate of aggressive behavior among epithelioid angiomyolipomas, even when showing morphologic features previously reported to portend aggressive clinical behavior, is very low.Modern Pathology advance online publication, 19 April 2013; doi:10.1038/modpathol.2013.72.
  Modern Pathology 04/2013; · 4.79 Impact Factor
• Article: Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model.

  Jonathan L Silberstein, Preston C Sprenkle, Daniel Su, Nicholas E Power, Tatum V Tarin, Paula Ezell, Daniel D Sjoberg, Andrew Feifer, Martin Fleisher, Paul Russo, Karim A Touijer
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  ABSTRACT: OBJECTIVES: To test a novel porcine two-kidney model for evaluating the effect of controlled acute kidney injury (AKI) related to induced unilateral ischaemia on both renal units (RUs) To use neutrophil gelatinase-associated lipocalin (NGAL) and physiological serum and urinary markers to assess AKI and renal function. METHODS: Twelve female Yorkshire pigs had bilateral cutaneous ureterostomies placed laparoscopically with identical duration of pneumoperitoneum for all cases. An experimental group (n = 9) underwent induced unilateral renal ischaemia with left hilar clamping of timed duration (15, 30, 60 min) and a control group (n = 3) had no induced renal ischaemia. Urine was collected and analysed from each RU to assess creatinine and NGAL concentration preoperatively and at multiple postoperative time points. Serum was collected and analysed daily for creatinine and NGAL levels. Statistical comparisons were made using the rank-sum and sign-rank tests. RESULTS: Three pigs were excluded because of intra-operative and postoperative complications. In the RUs that experienced renal ischaemia (n = 7),the median urine volume was lower (P = 0.04) at 6, 12, 24 and 48 h and the median NGAL concentration was higher (P = 0.04) at 12 and 48 h compared with the RUs of control pigs that experienced no renal ischaemia (n = 2). When comparing the ischaemic (left) RU of the pigs in the experimental group with their contralateral non-ischaemic (right) RU, ischaemic RUs had a lower median cumulative urine volume at 6, 12, 24 and 48 h (P = 0.05) and a higher median NGAL concentration at 12, 24 and 48 h (P < 0.05). At 48 h, no significant increase was found in serum NGAL in pigs in the experimental group compared with controls (P = 0.2). Creatinine clearance (CC) was lower in ischaemic RUs compared with non-ischaemic RUs 1 day after surgery (P = 0.04) with decreasing CC as the duration of ischaemia increased. CONCLUSIONS: We have developed a promising novel small-scale pilot surgical model that allowed the evaluation of bilateral RU function separately during and after unilateral renal ischaemia. The induction of unilateral renal ischaemia corresponds with physiological changes in both the ischaemic and contralateral RU. AKI as measured by increases in NGAL and decreased renal function as measured by decreases in CC, are specific to the RU exposed to ischaemia.
  BJU International 03/2013; · 2.84 Impact Factor
• Article: Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years.

  Anders Christensson, Caroline Savage, Daniel D Sjoberg, Angel M Cronin, M Frank O'Brien, William Lowrance, Peter M Nilsson, Andrew J Vickers, Paul Russo, Hans Lilja
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  ABSTRACT: Patients with chronic renal failure show a greater incidence of malignancies. We evaluated whether moderately impaired renal function at baseline influenced risk of all cancers during long-term follow in young persons. Our cohort included 33,346 subjects, aged 26-61 years at baseline, in a representative, population-based study enrolling subjects from 1974 to 1992. Median follow-up time was 28 years. Plasma creatinine was analysed as a single measure at baseline. Incident cases of cancer were identified from the Swedish Cancer Registry. We studied 24,552 subjects from the cohort. To account for the unique sampling design, participants were divided by sex and age at baseline into 1,132 older men (age 60), 14,254 younger men (age 40-52), 7,498 older women (age 47-57) and 1,688 younger women (age 35-43). Glomerular filtration rate (GFR) was estimated using the CKD-EPI formula. Patients were classified as having either normal to mildly impaired kidney function (eGFR≥60 mL/min/1.73m2 ), or moderate kidney dysfunction (eGFR<60 mL/min/1.73m2 ). We calculated the risk of all cancers using competing risks regression. Overall, 6,595 participants were diagnosed with cancer, and 854 subjects (3.5%) had moderately impaired renal dysfunction at baseline. There was a significant association between moderately decreased GFR and subsequent risk of kidney cancer in younger men (hazard ratio, 3.38; 95% CI, 1.48 to 7.71; P=0.004). However, we found no association with overall long-term cancer risk. Our confirmation of an association between moderately impaired renal function and risk of kidney cancer in younger men requires further exploration of high-risk groups and biological mechanisms. © 2013 Wiley Periodicals, Inc.
  International Journal of Cancer 03/2013; · 5.44 Impact Factor
• Article: Trends in Partial and Radical Nephrectomy: An Analysis of Case Logs from Certifying Urologists.

  Stephen A Poon, Jonathan L Silberstein, Ling Y Chen, Behfar Ehdaie, Philip H Kim, Paul Russo
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  ABSTRACT: PURPOSE: Surgical treatment options for renal masses include radical versus partial nephrectomy and the open versus laparoscopic approach. Using American Board of Urology case log data, we investigated contemporary trends in these treatment options and how surgeon and practice characteristics may influence these trends. MATERIALS AND METHODS: Annualized case log data for nephrectomies were obtained from the American Board of Urology for all urologists certifying or recertifying, from 2002 to 2010. We evaluated the trends in nephrectomy use. Logistic regressions were used to evaluate surgeon and practice characteristics as predictors for partial and laparoscopic procedures. RESULTS: From the 3,852 case logs submitted by non-pediatric urologists, 48,384 nephrectomies were analyzed. From 2002 to 2010, the proportion of annual nephrectomies that were performed as open radical nephrectomies gradually decreased from 54% to 29%. During the same period, there was a moderate gradual increase of laparoscopic radical nephrectomy usage, from 30% to 39%. The proportion of open partial nephrectomy remained stable at 15% while laparoscopic partial nephrectomy increased from 2% to 17%. On multivariable analysis, usage of partial nephrectomy and laparoscopy was predicted by a urologist's annual nephrectomy volume, initial or recertification status, subspecialty, practice area size, and geographic region. CONCLUSIONS: Since 2002, usage of laparoscopic nephrectomy and partial nephrectomy has increased. However, the diffusion of these techniques is not uniform. Initial certification, higher surgical volume, and practicing in areas over 1,000,000 and northeast region were associated with higher usage of laparoscopy and partial nephrectomy. Factors that affect the adoption of these techniques require further research.
  The Journal of urology 02/2013; · 4.02 Impact Factor
• Article: A Review of Contemporary Data on Surgically Resected Renal Masses-Benign or Malignant?

  Anthony T Corcoran, Paul Russo, William T Lowrance, Aviva Asnis-Alibozek, John A Libertino, Daniel A Pryma, Chaitanya R Divgi, Robert G Uzzo
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  ABSTRACT: OBJECTIVE: To 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. MATERIALS AND METHODS: PubMed 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. RESULTS: We 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; SD = 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%). CONCLUSION: Benign 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.
  Urology 02/2013; · 2.43 Impact Factor
• Article: Renal Cell Carcinoma: Role of MR Imaging in the Assessment of Muscular Venous Branch Invasion.

  Christoph A Karlo, Pier Luigi Di Paolo, Olivio F Donati, Paul Russo, Satish Tickoo, Hedvig Hricak, Oguz Akin
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  ABSTRACT: Purpose:To assess diagnostic performance and interreader agreement of tumor-to-sinus distance measurements and visual assessment of renal sinus fat invasion at T2-weighted magnetic resonance (MR) imaging as predictors of muscular venous branch invasion (MVBI) in patients with renal cell carcinoma (RCC).Materials and Methods:The institutional review board approved this retrospective study and waived the informed consent requirement. The study was HIPAA compliant. A total of 186 consecutive patients underwent preoperative 1.5-T MR imaging; 188 RCCs were identified. Blinded to histopathologic information, two readers independently measured the tumor-to-sinus distance and assessed renal sinus fat invasion on transverse and coronal T2-weighted MR images. Interreader agreement (intraclass correlation coefficient, Cohen κ) and performance characteristics of imaging tests were calculated. Histopathologic findings served as the standard of reference.Results:Histopathologic findings indicated MVBI in 35% (66 of 188) of tumors. At imaging, all tumors with MVBI had a tumor-to-sinus distance of 0 mm. All tumors with renal sinus fat invasion at imaging had MVBI. Sensitivity and specificity for the detection of renal sinus fat invasion were 100% (95% confidence interval [CI]: 92%, 100%) and 94% (95% CI: 89%, 98%). In the absence of renal sinus fat invasion at imaging, a tumor-to-sinus distance of 0 mm was associated with MVBI in 21% (18 of 86) of cases. Interreader agreement for quantitative (intraclass correlation coefficient = 0.92; 95% CI: 0.89, 0.94) and qualitative (κ = 0.89; 95% CI: 0.81, 0.96) assessments was excellent.Conclusion:Tumor-to-sinus distance measurements and the assessment of renal sinus fat invasion at T2-weighted MR imaging can be used reliably to rule out MVBI in patients with RCC.© RSNA, 2013.
  Radiology 02/2013; · 5.73 Impact Factor
• Article: Long-term mortality in patients with germ cell tumors: Effect of primary cancer site on cause of death.

  Shaheen R Alanee, Darren R Feldman, Paul Russo, Badrinath Konety
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  ABSTRACT: OBJECTIVES: To examine the effect of extragonadal tumor site on the risk for cardiovascular, hematopoietic malignancies, and solid cancer-related causes of death. PATIENTS AND METHODS: Male patients diagnosed with germ cell tumors (GCTs) between 1973 and 2008 were identified from the Surveillance, Epidemiology and End Results database, and stratified by the site of primary cancer (mediastinal and nonmediastinal extragonadal vs. gonadal). Using competing risk analysis restricted to events that happened at least 5 years after diagnosis, we examined the possible effect of primary tumor site on the risk for death related to hematopoietic malignancies, cardiovascular disorders, and solid cancers in the study cohort. RESULTS: Of 37,283 patients included in our analysis, 17,715 were diagnosed with nonseminomas and 19,568 with seminomas. Eight hundred and twenty four patients (2%) were diagnosed with primary mediastinal GCTs and 1,469 (4%) with nonmediastinal extragonadal tumors. Patients with mediastinal GCTs had an increased risk for death related to hematopoietic malignancies (hazard ratio [HR] = 8.84; 95% confidence interval [CI]: 3.16-24; P<0.0001) and cardiovascular disorders (HR = 4.45; 95% CI: 2.52-8.0; P<0.0001), but no significant difference in risk of dying of solid cancers (HR = 1.46; 95% CI: 0.36-5.9; P = 0.59) compared to patients with gonadal GCTs. Patients with nonmediastinal extragonadal GCTs had a significantly increased risk for dying of cardiovascular disorders (HR = 2.75; 95% CI: 1.67-4.51; P<0.0001), but not a significantly different risk for dying of hematopoietic malignancies (HR = 0.93; 95% CI: 0.13-6.84; P = 0.94) or solid cancers (HR = 1.45; 95% CI: 0.68-5.0; P = 0.23) compared with patients with gonadal GCTs. CONCLUSIONS: Patients with GCTs and extragonadal primary sites have an increased risk for death from cardiovascular disease and hematopoietic malignancies compared to those with gonadal GCTs, and could benefit from more intense preventive measures to decrease the risk of death related to these disorders.
  Urologic Oncology 02/2013; · 3.22 Impact Factor
• Article: Urine Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a Marker for Acute Kidney Injury in Kidney Surgery Patients.

  Preston C Sprenkle, James Wren, Alexandra C Maschino, Andrew Feifer, Nicholas Power, Tarek Ghoneim, Itay Sternberg, Martin Fleisher, Paul Russo
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  ABSTRACT: PURPOSE: Evaluate uNGAL as a marker for AKI in patients undergoing PN to identify the preoperative clinical features and surgical factors during PN that are associated with renal injury as measured by increased uNGAL levels compared to controls. METHODS: Using RN and thoracic surgery patients as control groups, we prospectively collected and analyzed urine and serum of PN, RN, and thoracic surgery patients between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in uNGAL levels between the 3 surgical groups were analyzed using a GEE model. The PN group was subdivided based on preoperative eGFR <60 or ≥60 ml/min/1.73m2. RESULTS: Of 162 patients included in the final analysis, >65% had CVD, and median eGFR was >60 ml/min/1.73m2 for all groups (RN=61, PN=78, thoracic surgery=84.5 ml/min/1.73m2). Preoperatively, a 10-unit increase in eGFR was associated with a 4- unit decrease in uNGAL in the PN group. Postoperatively, uNGAL levels in the PN group were not higher than thoracic surgery or RN control groups, and did not correlate with duration of ischemia. PN patients with preoperative eGFR <60 developed higher uNGAL levels postoperatively compared to those with a higher preoperative eGFR. CONCLUSION: uNGAL does not appear to be a useful marker for detection of renal injury in healthy PN patients. However, patients with poorer preoperative renal function have higher baseline uNGAL levels and appear more susceptible to AKI as detected by uNGAL levels and AKIN criteria compared to those with normal eGFR.
  The Journal of urology 02/2013; · 4.02 Impact Factor
• Article: Multiphasic contrast-enhanced MRI: Single-slice versus volumetric quantification of tumor enhancement for the assessment of renal clear-cell carcinoma fuhrman grade.

  Hebert Alberto Vargas, Holly G Delaney, Eithne M Delappe, Ya Wang, Junting Zheng, Chaya S Moskowitz, Yongqiang Tan, Binsheng Zhao, Lawrence H Schwartz, Hedvig Hricak, Paul Russo, Oguz Akin
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  ABSTRACT: PURPOSE: To assess the association between clear-cell carcinoma pathology grade at nephrectomy and magnetic resonance imaging (MRI) tumor enhancement. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study and waived the informed consent requirement. In all, 32 patients underwent multiphase contrast-enhanced MRI prior to nephrectomy. MRI tumor enhancement was measured using two approaches: 1) the most enhancing portion of the tumor on a single slice and 2) volumetric analysis of enhancement in the entire tumor. Associations between pathological grade, tumor size, and enhancement were evaluated using the Kruskal-Wallis test and generalized logistic regression models. RESULTS: No significant association between pathology grade and enhancement was found when measurements were made on a single slice. When measured in the entire tumor, significant associations were found between higher pathology grades and lower mean, median, top 10%, top 25%, and top 50% tumor enhancement (P < 0.001-0.002). On multivariate analysis the association between grade and enhancement remained significant (P = 0.041-0.043), but tumor size did not make an additional contribution beyond tumor enhancement alone in differentiating between tumor grades. CONCLUSION: There is significant association between tumor grade and enhancement, but only when measured in the entire tumor and not on the most enhancing portion on a single slice. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
  Journal of Magnetic Resonance Imaging 11/2012; · 2.70 Impact Factor
• Article: Reply from Authors re: James W.F. Catto, Shahrokh F. Shariat. The Changing Face of Renal Cell Carcinoma: The Impact of Systematic Genetic Sequencing on Our Understanding of This Tumor's Biology. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2012.09.049: Genetic Stratification of Clear Cell Renal Carcinomas Presenting as Small Renal Masses.

  A Ari Hakimi, Victor E Reuter, Paul Russo, James J Hsieh
  European urology 10/2012; · 7.67 Impact Factor
• Article: Clinical and Pathologic Impact of Select Chromatin-modulating Tumor Suppressors in Clear Cell Renal Cell Carcinoma.

  A Ari Hakimi, Ying-Bei Chen, James Wren, Mithat Gonen, Omar Abdel-Wahab, Adriana Heguy, Han Liu, Shugaku Takeda, Satish K Tickoo, Victor E Reuter, Martin H Voss, Robert J Motzer, Jonathan A Coleman, Emily H Cheng, Paul Russo, James J Hsieh
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  ABSTRACT: BACKGROUND: Historically, VHL was the only frequently mutated gene in clear cell renal cell carcinoma (ccRCC), with conflicting clinical relevance. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC including PBRM1, SETD2, BAP1, and KDM5C. PBRM1, SETD2, and BAP1 are located in close proximity to VHL within a commonly lost (approximately 90%) 3p locus. To date, the clinical and pathologic significance of mutations in these novel candidate tumor suppressors is unknown. OBJECTIVE: To determine the frequency of and render the first clinical and pathologic outcome associated with mutations of these novel candidate tumor suppressors in ccRCC. DESIGN, SETTING, AND PARTICIPANTS: Targeted sequencing was performed in 185 ccRCCs and matched normal tissues from a single institution. Pathologic features, baseline patient characteristics, and follow-up data were recorded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The linkage between mutations and clinical and pathologic outcomes was interrogated with the Fisher exact test (for stage and Fuhrman nuclear grade) and the permutation log-rank test (for cancer-specific survival [CSS]). RESULTS AND LIMITATIONS: PBRM1, BAP1, SETD2, and KDM5C are mutated at 29%, 6%, 8%, and 8%, respectively. Tumors with mutations in PBRM1 or any of BAP1, SETD2, or KDM5C (19%) are more likely to present with stage III disease or higher (p=0.01 and p=0.001, respectively). Small tumors (<4cm) with PBRM1 mutations are more likely to exhibit stage III pathologic features (odds ratio: 6.4; p=0.001). BAP1 mutations tend to occur in Fuhrman grade III-IV tumors (p=0.052) and are associated with worse CSS (p=0.01). Clinical outcome data are limited by the number of events. CONCLUSIONS: Most mutations of chromatin modulators discovered in ccRCC are loss of function, associated with advanced stage, grade, and possibly worse CSS. Further studies validating the clinical impact of these novel mutations and future development of therapeutics remedying these tumor suppressors are warranted.
  European urology 09/2012; · 7.67 Impact Factor
• Article: Renal cortical tumors: use of multiphasic contrast-enhanced MR imaging to differentiate benign and malignant histologic subtypes.

  Hebert Alberto Vargas, Joshua Chaim, Robert A Lefkowitz, Yulia Lakhman, Junting Zheng, Chaya S Moskowitz, Michael J Sohn, Lawrence H Schwartz, Paul Russo, Oguz Akin
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  ABSTRACT: To investigate the use of quantitative multiphasic contrast material-enhanced magnetic resonance (MR) imaging in differentiating between common benign and malignant histologic subtypes of renal cortical tumors. The institutional review board waived informed consent and approved this retrospective HIPAA-compliant study of 138 patients who underwent preoperative contrast-enhanced MR imaging during the period of January 2004-December 2008. At surgery, 152 renal tumors were identified (77 clear cell, 22 papillary, 18 chromophobe, and 10 unclassified carcinomas; 16 oncocytomas; nine angiomyolipomas). Three readers independently identified and measured the most-enhanced area in each tumor and placed corresponding regions of interest in similar positions on images from the precontrast, corticomedullary, nephrographic, and excretory phases. The percentage change in signal intensity (%SI change) between precontrast imaging and each postcontrast phase was calculated. Interreader agreement was evaluated by using the overall concordance correlation coefficient (OCC). A linear mixed-effects model was used to estimate and compare the trajectories of the means of log %SI change across all phases between the six histologic subtypes. Interreader agreement was substantial to almost perfect (OCC, 0.77-0.88). The %SI change differed significantly between clear cell carcinomas and papillary and chromophobe carcinomas in all phases of enhancement (P < .0001-.0120). In addition, %SI change was significantly higher in angiomyolipomas than in clear cell carcinomas, but only in the corticomedullary phase (P = .0231). Enhancement did not differ significantly between clear cell carcinoma and oncocytoma in any phase (P = .2081-.6000). Quantitative multiphase contrast-enhanced MR imaging offers a widely available, reproducible method to characterize several histologic subtypes of renal cortical tumors, although it does not aid differentiation between clear cell carcinomas and oncocytomas.
  Radiology 07/2012; 264(3):779-88. · 5.73 Impact Factor
• Article: Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC).

  Jonathan L Silberstein, Ari Adamy, Alexandra C Maschino, Behfar Ehdaie, Tullika Garg, Ricardo L Favaretto, Tarek P Ghoneim, Robert J Motzer, Paul Russo
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  ABSTRACT: Study Type - Harm (case series) Level of Evidence  4 What's known on the subject? and What does the study add? Radical nephrectomy for patients with metastatic renal cell carcinoma results in greater rates of morbidity than for those with less advanced disease. This study systematically characterizes complications associated with nephrectomy for metastatic RCC and identifies patient and disease characteristics that are associated with a greater risk of developing complications. Overall complications were relatively frequent, but major complications (grade 3 or greater) were rare. Increasing age and worsening performance status were associated with increased probability of complications. When complications were sustained, patients were less likely to receive systemic therapy in a timely fashion. These observations may influence the timing or patient selection for surgery or systemic therapy. •  To evaluate and identify factors predictive for morbidity after radical nephrectomy in patients with metastatic renal cell carcinoma (mRCC). •  We identified patients with mRCC who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1989 and 2009. •  Postoperative complications were characterised using a modified version of the Clavien-Dindo classification system. •  Patient and disease characteristics, including a previously validated MSKCC risk-stratification system using calcium, haemoglobin (Hb), lactate dehydrogenase, and Karnofsky Performance Status (KPS), were evaluated as predictors of postoperative complications using univariate and multivariable logistic regression models. •  The area under the receiver operating characteristic curve (AUC) was calculated for each model to assess predictive accuracy and corrected for overfit using 10-fold cross validation. •  Over the study period, 195 patients with mRCC underwent nephrectomy; 53 (27%) developed grade ≥2 complications within 8 weeks of surgery. •  Pulmonary, thromboembolic events and anaemia requiring transfusion were the most common types of complications after nephrectomy in the metastatic setting. •  In univariate analysis, age, low albumin, low KPS, high corrected serum calcium, low serum Hb, and unfavourable MSKCC risk score were predictive of complications. •  Patients who sustained postoperative complications were less likely to receive systemic therapy within 56 days (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.12-0.86; P= 0.024). •  A multivariable model containing KPS (OR 14.5; 95%CI 4.34-48.6; P < 0.001) and age (OR 1.04; 95%CI 1.01-1.08; P= 0.014) showed the greatest predictive accuracy (corrected AUC 0.72; 95%CI 0.63-0.80) for postoperative complications. •  Postoperative complications after radical nephrectomy in the setting of mRCC are common and occur frequently in older patients and those with worse KPS. •  These complications are important because they may delay or deny receipt of subsequent systemic therapy.
  BJU International 05/2012; 110(9):1276-82. · 2.84 Impact Factor
• Article: Reply.

  Nicholas E Power, Jonathan L Silberstein, Daniel Thorner, Tatum Tarin, Adriana Wong, Karim A Touijer, Paul Russo, Jonathan A Coleman, Alexandra C Maschino, Caroline Savage
  Urology 04/2012; 79(4):826. · 2.43 Impact Factor
• Article: Intraoperative mannitol use does not improve long-term renal function outcomes after minimally invasive partial nephrectomy.

  Nicholas E Power, Alexandra C Maschino, Caroline Savage, Jonathan L Silberstein, Daniel Thorner, Tatum Tarin, Adriana Wong, Karim A Touijer, Paul Russo, Jonathan A Coleman
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  ABSTRACT: To evaluate intravenous mannitol during minimally invasive partial nephrectomy (PN) by comparing the renal function outcomes of the patients who received it versus those who did not. Of 285 consecutive elective minimally invasive PN cases from February 2005 to July 2010, 164 patients (58%) were treated with mannitol. We compared the renal function recovery using a multivariate generalized estimating equation linear model of estimated glomerular filtration rate (eGFR) controlling for nephrometry complexity, preoperative eGFR, American Society of Anesthesiologists score, ischemia time, estimated blood loss, age, and sex. Sensitivity analyses were performed to adjust for cold ischemia and individual surgeon differences corrected for year of surgery. Of the 285 patients who underwent minimally invasive treatment, 164 received mannitol and 121 did not. Those who received mannitol had a better preoperative eGFR (median 72 vs 69 mL/min/m(2), P = .046), less complex nephrometry scores (P = 0.051), and were less likely to have an American Society of Anesthesiologists score of ≥ 3 (42% vs 54%, P = .005). Renal function recovery was similar in both groups (estimated effect of mannitol -0.7 mL/min/m(2), 95% confidence interval -3.6-2.2, P = .6). At no point in the postoperative period did mannitol make a significant difference in the eGFR according to the generalized estimating equation model after adjusting for multiple potential renal function confounders. Mannitol use did not influence renal function recovery within 6 months of minimally invasive PN as measured by the eGFR in our analysis. An appropriately designed prospective study of mannitol is being conducted to validate its use during PN.
  Urology 04/2012; 79(4):821-5. · 2.43 Impact Factor
• Article: Comparison of open and minimally invasive partial nephrectomy for renal tumors 4-7 centimeters.

  Preston C Sprenkle, Nicholas Power, Tarek Ghoneim, Karim A Touijer, Guido Dalbagni, Paul Russo, Jonathan A Coleman
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  ABSTRACT: Indications for partial nephrectomy (PN) in the treatment of renal cell carcinoma are evolving, particularly for larger, more complex tumors. Compare single-institution outcomes for minimally invasive partial nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors>4-7 cm. A total of 2290 patients underwent PN from 2002 to 2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4-7 cm renal cortical tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and 37 laparoscopic procedures). Perioperative management was uniform on the clinical pathway. Perioperative data, clinicopathologic variables, complications within 30 d, and oncologic outcomes were reviewed. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Complications were reported from prospectively collected data based on a modified Clavien system. The Fisher exact and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan-Meier methods were used to estimate survival. Median follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no statistically significant differences in age, gender, preoperative American Society of Anesthesiologists score, laterality, histologic subtype, tumor size, tumor stage, or margin status between procedures. Univariate analysis revealed significantly greater values in the OPN group for preoperative eGFR, renal artery clamp time, estimated blood loss, use of renal hypothermia, and length of stay. Differences in overall survival and recurrence-free survival were not statistically significant; however, short median follow-up times limit comparison. There was no significant difference in the number of complications grade≥3 (p=0.1) or urine leaks requiring intervention (p=0.7). Limitations include the retrospective nature of the study and the possibility of selection bias. OPN and MIPN procedures performed in patients with tumors>4-7 cm offer acceptable and comparable results in terms of operative, functional, and convalescence measures, regardless of approach.
  European urology 12/2011; 61(3):593-9. · 7.67 Impact Factor
• Article: Evaluation of renal masses with contrast-enhanced ultrasound: initial experience.

  Scott Gerst, Lucy E Hann, Duan Li, Mithat Gonen, Satish Tickoo, Michael J Sohn, Paul Russo
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  ABSTRACT: Nearly 25% of solid renal tumors are indolent cancer or benign and can be managed conservatively in selected patients. This prospective study was performed to determine whether preoperative IV microbubble contrast-enhanced ultrasound can be used to differentiate indolent and benign renal tumors from more aggressive clear cell carcinoma. Thirty-four patients with renal tumors underwent preoperative gray-scale, color, power Doppler, and octafluoropropane microbubble IV contrast-enhanced ultrasound. Three blinded radiologists reading in consensus compared rate of contrast wash-in, grade and pattern of enhancement, and contrast washout compared with adjacent parenchyma. Contrast ultrasound findings were compared with surgical histopathologic findings for all patients. The 34 patients had 23 clear cell carcinomas, three type 1 papillary carcinomas, one chromophobe carcinoma, one clear rare multilocular low-grade malignant tumor, two unclassified lesions, three oncocytomas, and one benign angiomyolipoma. The combination of heterogeneous lesion echotexture and delayed lesion washout had 85% positive predictive value, 43% negative predictive value, 48% sensitivity, and 82% specificity for predicting whether a lesion was conventional clear cell carcinoma or another tumor. Diminished lesion enhancement grade had 75% positive predictive value, 81% negative predictive value, 55% sensitivity, and 91% specificity for non-clear cell histologic features, either benign or low-grade malignant. Combining delayed washout with quantitative lesion peak intensity of at least 20% of kidney peak intensity had 91% positive predictive value, 40% negative predictive value, 63% sensitivity, and 80% specificity in the prediction of clear cell histologic features. Ultrasound features of gray-scale heterogeneity, lesion washout, grade of contrast enhancement, and quantitative measure of peak intensity may be useful for differentiating clear cell carcinoma and non-clear cell renal tumors.
  American Journal of Roentgenology 10/2011; 197(4):897-906. · 2.78 Impact Factor
• Article: Oncological outcomes of partial nephrectomy for renal carcinoma greater than 4 cm.

  Paul Russo
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  ABSTRACT: To provide the clinical evidence and benefits of performing partial nephrectomy for renal tumors greater than 4 cm. Partial nephrectomy was historically performed only for the essential indications of a tumor in a functional or anatomical solitary kidney or in the face of bilateral renal tumors. Partial nephrectomy has now emerged as an oncologically equivalent operation to radical nephrectomy for T1a tumors (<4 cm) with the added benefit of renal functional preservation which can prevent or delay the onset of chronic kidney disease (CKD). CKD is an independent risk factor for hospitalization events, cardiovascular disease, and worse overall survival. Recent evidence has demonstrated that partial nephrectomy also provides equivalent oncological results for larger renal tumors including those of 4-7 cm and even for greater than 7 cm, whenever technically feasible with the continued added benefit of renal functional preservation. Partial nephrectomy is effectively performed using both open surgical techniques and increasingly by minimally invasive approaches although the latter is technically challenging. Despite the mounting clinical evidence that partial nephrectomy is an effective and preferable approach to the T1 renal mass, it remains markedly underutilized in the USA and abroad. The overzealous use of radical nephrectomy for the T1 renal mass, by whatever surgical approach, must now be considered detrimental to the long-term health of the kidney tumor patient.
  Current opinion in urology 09/2011; 21(5):362-7. · 2.50 Impact Factor
• Article: Editorial comment.

  Paul Russo
  Urology 09/2011; 78(3):559-60; author reply 560. · 2.43 Impact Factor