Christopher G Wood

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (271)1446.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate how many patients could have undergone PN instead of RN before and after neoadjuvant axitinib therapy, as assessed by 5 independent urologic oncologists, and to study the variability of inter-observer agreement.Patients and Methods Pre- and post systemic treatment CT scans from 22 patients with ccRCC in a phase II neoadjuvant axitinib trial were reviewed by 5 independent urologic oncologists. RENAL score and Kappa statistics were calculated.ResultsMedian RENAL score changed from 11 pre-treatment to 10 post-treatment, p=0.0017. Five tumors with moderate-complexity pre-treatment remained moderate-complexity post-treatment. Of 17 tumors with high-complexity pre-treatment, 3 became moderate-complexity post-treatment. Overall kappa statistic was 0.611. Moderate-complexity kappa was 0.611 vs. high-complexity kappa of 0.428. Pre-treatment kappa was 0.550 vs. post-treatment of 0.609. After treatment with axitinib, all 5 reviewers agreed that only 5 patients required RN (instead of 8 pre-treatment) and that 10 patients could now undergo PN (instead of 3 pre-treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib.Conclusions There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant therapy, it remains difficult to identify these patients a priori.This article is protected by copyright. All rights reserved.
    BJU International 06/2015; DOI:10.1111/bju.13188 · 3.13 Impact Factor
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    ABSTRACT: PurposeMetastases to the kidney are a rare entity, historically described in autopsy studies. The primary aim of this study was to describe the presentation, treatment, and outcomes of patients with metastatic tumors to the kidney treated at a tertiary referral center.Patients and Methods We retrospectively identified 151 patients diagnosed with a primary non-renal malignancy with renal metastasis. Clinical, radiographic and pathologic characteristics were assessed. Overall survival (OS) was calculated using Kaplan-Meier methods.ResultsMedian patient age was 56.7 years. The most common presenting symptoms were flank pain (30%), hematuria (16%) and weight loss (12%). Most primary cancers were carcinomas (80.8%). The most common primary tumor sites were lung (43.7%), colorectal (10.6%), ENT (6%), breast (5.3%), soft tissue (5.3%), and thyroid (5.3%). Renal metastases were typically solitary (77.5%). Concordance between radiologist and clinician imaging assessment was 54.0%. Three ablations and 48 nephrectomies were performed. For non-surgical patients, renal metastasis diagnosis was made with FNA or biopsy. Median OS from primary tumor diagnosis was 3.08 years and median OS from time of metastatic diagnosis was 1.13 years. For patients treated with surgery, median OS from primary tumor diagnosis was 4.81 years, and OS from metastatic diagnosis was 2.24 years.Conclusions Metastases to the kidney are a rare entity. Survival appears to be longer in patients who are candidates for, and are treated with surgery. Surgical intervention in carefully selected patients with oligometastatic disease and good performance status should be considered. A multi-disciplinary approach with input from urologists, oncologists, radiologists, and pathologists is needed to achieve the most optimal outcomes for this specific patient population.This article is protected by copyright. All rights reserved.
    BJU International 06/2015; DOI:10.1111/bju.13194 · 3.13 Impact Factor
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    ABSTRACT: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is associated with higher stage of presentation and worse survival. The objective of this study was to examine the clinicopathologic characteristics associated with overall survival (OS), specifically examining the percentage of sarcomatoid component (PSC). We reviewed clinicopathologic data for all nephrectomized patients with confirmed sRCC. Histologic slides were rereviewed by dedicated genitourinary pathologists to ascertain PSC. Patient characteristics were tabulated overall and by disease stage. Cutpoints in the PSC providing a meaningful difference in OS were identified by recursive partitioning analysis (RPA). Factors selected included age group, gender, race, clinical stage, tumor histology, presurgical systemic therapy, lymphovascular invasion, and tumor size. The Kaplan-Meier method and log-rank test were used to assess differences in OS. Among 186 patients with sRCC, 64 (34%) had localized, and 122 (66%) had metastatic disease at presentation. Patients had primarily clear cell histology (73%). Median follow-up was 12.1 months (range: 0.1-242.2mo). Median OS was 12.6 months (95% CI: 10.7-14.9mo). Univariate RPA identified a PSC cutpoint of 10% as prognostically significant. Patients with PSC>10% were at higher risk of death when compared with patients with PSC≤10% (45% vs. 61% 1-y OS; P = 0.04). Multivariate RPA revealed that tumor size, presence of metastatic disease, and PSC were significantly associated with OS. Among 4 identified groups, patients with localized disease and tumor size≤10cm were most likely to be alive at 1 year (89%), and patients with metastatic disease and PSC>40% were least likely to be alive at 1 year (28%; P<0.001). PSC appears to be a prognostic factor in patients with sRCC, with larger percentage of involvement portending a worse survival, especially in patients with metastatic disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 05/2015; DOI:10.1016/j.urolonc.2015.04.011 · 3.36 Impact Factor
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    ABSTRACT: Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown. We prospectively defined the incidence of cardiotoxicity amongst resected, high-risk RCC patients treated with these agents. Sunitinib, sorafenib, or placebo was administered for up to 12 months in patients with high-risk, resected RCC. LVEF was measured by multi-gated acquisition (MUGA) scans at standard intervals. Additional CV adverse events were reported according to NCI Common Terminology Criteria for Adverse Events (CTCAE). Among 1,943 patients randomized, 1,599 had at least 1 post-baseline MUGA. Within 6 months, 21 patients (1.3%) experienced a cardiac event, defined as an LVEF decline from baseline that was >15% and below the institutional lower limit of normal. Nine of 513 (1.8%) patients were on sunitinib; 7 of 508 (1.4%) on sorafenib; and 5 of 578 (0.9%) on placebo (p=0.28 and 0.56 comparing sunitinib and sorafenib to placebo, respectively). With dose interruption or adjustment, 16 of the 21 recovered their LVEF to >50%. The incidence of symptomatic heart failure, arrhythmia, or myocardial ischemia did not differ among groups. In the adjuvant setting, we prospectively define low incidence of cardiotoxicity with sunitinib and sorafenib. These findings may be related to close CV monitoring, or potentially to fewer CV comorbidities in our non-metastatic population. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 05/2015; DOI:10.1158/1078-0432.CCR-15-0215 · 8.19 Impact Factor
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    ABSTRACT: Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma (ccRCC). Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid ccRCC and compare them to non-sarcomatoid ccRCC. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid ccRCC (n=43) and non-sarcomatoid ccRCC (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid ccRCC (n=10) and advanced non-sarcomatoid ccRCC (n=155). The epithelioid and sarcomatoid components of sarcomatoid ccRCC had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid ccRCC. Prognostic ccRCC gene expression profiles were shared by the biphasic components of sarcomatoid ccRCC and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid ccRCCs using RNA-seq. Sarcomatoid ccRCC is molecularly distinct from non-sarcomatoid ccRCC, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the need to modify the pathological grading system; and introduce the potential for candidate biomarkers to detect sarcomatoid change preoperatively without specifically sampling the S component. This article is protected by copyright. All rights reserved.
    05/2015; DOI:10.1002/cjp2.23
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    ABSTRACT: A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). A literature review was conducted. Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 04/2015; DOI:10.1016/j.eururo.2015.04.010 · 12.48 Impact Factor
  • The Journal of Urology 04/2015; 193(4):e761. DOI:10.1016/j.juro.2015.02.2228 · 3.75 Impact Factor
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    ABSTRACT: Surgical resection for renal cell carcinoma (RCC) with suprahepatic inferior vena cava tumor thrombus is associated with significant morbidity, yet there are currently no tools for preoperative prognostic evaluation. Our goal was to develop a preoperative multivariable model for prediction of survival and risk of major complications in patients with suprahepatic thrombi. We identified patients who underwent surgery for RCC with suprahepatic tumor thrombus extension from 2000 to 2013 at 4 tertiary centers. A Cox proportional hazard model was used for analysis of overall survival (OS) and logistic regression was used for major complications within 90 days of surgery (Clavien≥3A). Nomograms were internally calibrated by bootstrap resampling method. A total of 49 patients with level III thrombus and 83 patients with level IV thrombus were identified. During median follow-up of 24.5 months, 80 patients (60.6%) died and 46 patients (34.8%) experienced major complication. Independent prognostic factors for OS included distant metastases at presentation (hazard ratio = 2.52, P = 0.002) and Eastern Cooperative Oncology Group (ECOG) performance status (hazard ratio = 1.84, P<0.0001). Variables associated with increased risk of major complications on univariate analysis included preoperative systemic symptoms, level IV thrombus, and elevated preoperative alkaline phosphatase and aspartate transaminase levels; however, only systemic symptoms (odds ratio = 8.45, P<0.0001) was an independent prognostic factor. Preoperative nomograms achieved a concordance index of 0.72 for OS and 0.83 for major complications. We have developed and internally validated multivariable preoperative models for the prediction of survival and major complications in patients with RCC who have a suprahepatic inferior vena cava thrombus. If externally validated, these tools may aid in patient selection for surgical intervention. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 04/2015; 193(4):e763-e764. DOI:10.1016/j.juro.2015.02.2234 · 3.36 Impact Factor
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    ABSTRACT: Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We investigated the outcomes of patients with localized RPR treated with surgical resection. This was a retrospective single-institutional study of 102 patients with RPR treated with surgery from 1990-2014. Demographics, clinical and pathological features, location of RPR, perioperative complications were reported using descriptive statistics. Recurrence free survival (RFS) and cancer-specific survival (CSS) were studied using univariate and multivariate analyses. Median age at RPR diagnosis was 55 years (IQR 49-64). Sixty-two (60.8%) patients were pT3-4 and 20 (19.6%) were pN1. No patients had distant metastatic disease at time of RPR surgery. Median time from nephrectomy to RPR diagnosis was 19 months (IQR 5-38.8). The median size of resected RPR was 4.5cm (IQR 2.7-7). Median follow up after RPR surgery was 32 months (IQR 16-57). Metastatic progression was observed in 60 (58.8%) patients after RPR surgery. Neoadjuvant and salvage systemic therapy were administered in 46 (45.1%) and 48 (47.1%) patients, respectively. On multivariate analysis, pathological nodal stage at original nephrectomy and maximum diameter of RPR were identified as independent risk factors for cancer specific death. Clinico-pathological factors at the time of nephrectomy as well as RPR surgery are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR with acceptable complications, and still plays a dominant role in the management of isolated locally recurrent RCC. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of Urology 03/2015; 193(4). DOI:10.1016/j.juro.2015.02.2943 · 3.75 Impact Factor
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    ABSTRACT: We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLA-DQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immune-related pathway and genes in the etiology of RCC.
    Oncotarget 02/2015; 6(6):4097-109. · 6.63 Impact Factor
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    ABSTRACT: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size. Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urologic Oncology 02/2015; 33(4). DOI:10.1016/j.urolonc.2014.11.021 · 3.36 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer, and anti-angiogenic therapy is the current mainstay of treatment. RCC patients develop innate or adaptive resistance to anti-angiogenic therapy. There is a need to identify biomarkers which predict therapeutic resistance and guide combination therapy. We assessed the interaction between anti-angiogenic therapy and tumor immune microenvironment, and determined their impact on clinical outcome. Here we found that anti-angiogenic therapy treated RCC primary tumors demonstrated increased infiltration of CD4+ and CD8+ T lymphocytes, which was inversely related to patient overall survival (OS) and progression free survival (PFS). Furthermore, anti-angiogenic therapy treated specimens showed higher infiltration of CD4+FOXP3+ regulatory T cells (Tregs) and enhanced expression of checkpoint ligand programed death-ligand 1 (PD-L1). Both immunosuppressive features were correlated with T lymphocyte infiltration and were negatively related to patient survival. Treatment of RCC cell lines and RCC xenografts in immunodeficient mice with sunitinib also increased tumor PD-L1 expression. This study indicates that anti-angiogenic treatment may both positively and negatively regulate the tumor immune microenvironment. These findings generate hypotheses on resistance mechanisms to anti-angiogenic therapy, and will guide the development of combination therapy with PD-1/PD-L1 blocking agents. Copyright © 2015, American Association for Cancer Research.
    2015 Genitourinary Cancers Symposium of the American Society of Clinical Oncology, J Clin Oncol 33, 2015 (suppl 7; abstr 419); 02/2015
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    ABSTRACT: Variation of mitochondrial DNA copy number (mtDNAcn) in peripheral blood leukocytes (PBLs) has been associated with the risk of various cancers, including renal cell carcinoma (RCC). We assessed the association between mtDNAcn and clear cell RCC (ccRCC) risk in 608 cases and 629 controls frequency-matched on age and gender. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, BMI, smoking status, history of hypertension, total energy intake and physical activity. Our results suggest an association between low mtDNAcn and ccRCC risk (OR = 1.28, 95% CI: 0.97-1.68, P=0.09). Lower mtDNAcn was associated with increased ccRCC risk in younger individuals (Age<60, OR=1.68, 95% CI: 1.13-2.49, P=0.01), women (OR=1.66, 95% CI: 1.03-2.73, P=0.04), individuals without history of hypertension (OR=1.62, 95% CI: 1.09-2.41, P=0.02) and individuals with low physical activity levels (OR=1.55 95% CI: 1.02-2.37, P=0.05). We observed significant and marginally significant interactions between both age and history of hypertension and mtDNAcn in elevating ccRCC risk (P for interaction=0.04 and 0.07, respectively). Additionally, low mtDNAcn was associated with ccRCC risk in younger individuals with low levels of physical activity [ORs and 95% CI for medium and low physical activity levels respectively, 2.31 (1.18-4.52) and 2.09 (1.17-3.75), p-interaction 0.04]. To our knowledge, this is the first report to investigate the role of mtDNAcn in the clear cell renal cell carcinoma subtype and the first to suggest that this association may be modified by risk factors including age, gender, history of hypertension and physical activity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 12/2014; 36(2). DOI:10.1093/carcin/bgu248 · 5.27 Impact Factor
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    ABSTRACT: Background Renal neuroendocrine tumors (NET), comprising carcinoid tumors and small cell carcinomas, are a rare group of neoplasms. The rarity of these tumors poses a diagnostic and therapeutic challenge. Our purpose was to characterize the cases treated at a tertiary cancer center and to evaluate patients’ outcomes with the available treatment modalities. Methods This is a retrospective study of patients with renal NET seen at The University of Texas MD Anderson Cancer Center between January 1, 2001, and January 1, 2011. Patient and tumor data were analyzed by descriptive statistical methods. Results Three cases of carcinoid tumors and six cases of small cell carcinoma were identified. The median age at diagnosis was 53 years for patients with carcinoid and 65 years for patients with small cell carcinoma. The most common presenting symptoms were back pain, flank pain, and hematuria. The morphological appearance of the tumor cells and their immunohistochemical reactivity for neuroendocrine markers and cytokeratin helped establish the diagnosis. Nephrectomy was the mainstay of treatment for carcinoid tumors, yielding good long-term results, even in the presence of metastases. Surgery and chemotherapy were utilized for small cell carcinoma of the kidney. The median overall survival for patients with small cell carcinoma of the kidney was 17.3 months. Conclusion Renal carcinoid tumors are indolent and are associated with prolonged survival, while small cell carcinomas of the kidney are aggressive tumors with relatively short overall survival. Although palliative in nature, cytotoxic chemotherapy is the mainstay of therapy and is best given before surgery.
    Clinical Genitourinary Cancer 12/2014; DOI:10.1016/j.clgc.2014.06.008 · 1.69 Impact Factor
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    ABSTRACT: To validate the independent predictive value of Ki-67 in patients with high-grade upper tract urothelial carcinoma (UTUC). 475 patients from the international UTUC collaboration who underwent extirpative surgery for high-grade UTUC were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray (TMA) formed from this patient cohort. Ki-67 expression was assessed in a semi-quantitative fashion and considered overexpressed at a cut-off of 20%. Multivariate analyses (MVA) were performed to assess independent predictors of oncological outcomes and Harrell's C indices (HCI) were calculated for predictive models. Median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was overexpressed in 25.9% of patients. Ki-67 overexpression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ (CIS), and regional lymph node metastases. In Kaplan-Meier analyses, overexpressed Ki-67 was associated with worse recurrence-free (RFS) (HR 12.6, p<0.001) and cancer-specific survival (CSS) (HR 15.8, p<0.001). In MVA, Ki-67 was an independent predictor of RFS (HR 1.6, 95% CI 1.07-2.30, p=0.021) and CSS (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved HCI from 0.66 to 0.70 (p<0.0001) for both RFS and CSS in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for RFS and 0.81 to 0.83 (p=0.005) for CSS in our post-operative model. Ki-67 was validated as an independent prognostic predictor of RFS and CSS in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of Urology 11/2014; 193(5). DOI:10.1016/j.juro.2014.11.007 · 3.75 Impact Factor
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    ABSTRACT: To evaluate the prognostic value of altered mammalian target of rapamycin (mTOR) pathway biomarkers in upper tract urothelial carcinoma (UTUC). We performed a multi-institutional review of clinical and pathologic information on patients receiving extirpative surgery for UTUC from 1990 to 2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, phosphorylated-4EBP1, phosphorylated-AKT, PTEN, HIF-1a, raptor, and cyclin D was performed on tissue microarrays from radical nephroureterectomy (RNU) specimens. Prognostic markers were identified and the significance of altered markers was assessed with the Kaplan-Meier analysis and the Cox regression analysis. Six hundred twenty patients were included. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariate analysis, PI3K (odds ratio, 1.28; P = .001) and cyclin D (odds ratio, 3.45; P = .05) were significant predictors of clinical outcomes. Cumulative marker score was defined as low risk (no altered markers or 1 altered marker) or high risk (cyclin D and PI3K altered). Patients with high-risk marker score had a significantly higher proportion of high-grade disease (91% vs 71%; P <.001), non-organ-confined disease (61% vs 33%; P <.001), and lymphovascular invasion (35% vs 20%; P = .001). The Kaplan-Meier analysis demonstrated a significant difference in cancer-specific mortality (CSM) based on the risk groups. On Cox regression multivariate analysis for CSM incorporating non-organ-confined disease, grade, lymphovascular invasion, tumor architecture, and marker score, high-risk biomarker score was an independent predictor of CSM (hazard ratio, 1.5; 95% confidence interval, 1.04-2.3; P = .03). Alterations in mTOR pathway correlate with established adverse pathologic features and independently predict inferior oncologic outcomes. Incorporation of mTOR-based marker profiles may allow for enhanced patient counseling, risk stratification, and individualized treatment regimens. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urology 11/2014; 84(5):1134-40. DOI:10.1016/j.urology.2014.07.050 · 2.13 Impact Factor
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    ABSTRACT: Objective To characterize the clinical, radiologic and histologic features of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC), as well as oncologic outcomes.Patients and methodsThis is a single institution retrospective analysis of all MTSCC patients from 2002-2011.Patients were excluded if MTSCC could not be confirmed on pathology re-review (n=4).Clinical characteristics, pathology, imaging, and outcomes were reviewed for the 19 included patients.ResultsMedian age at diagnosis was 59 years (range 17-71) with a female predominance (78.9%).On contrast enhanced CT scan, MTSCC enhanced less than the cortex during the corticomedullary phase. Mean tumor attenuation was 36 HU (range 24-48), 67 HU (range 41-133), 89 HU (range 49-152), and 76 HU (range 52-106) in the precontrast, corticomedullary, nephrographic and excretory phases, respectively.Sixteen patients were treated with partial (N=5) or radical nephrectomy (N=11) for pT1(62.5%), pT2(31.3%), and pT3a disease(6.3%). One patient had active surveillance. Of 3 patients(13.0%) managed with energy ablation, there was one recurrence that was treated with salvage surgery.One patient(5.3%) had metastatic disease at diagnosis and died of disease 64.7 months later. A patient with a pT2bN0M0 MTSCC with sarcomatoid dedifferentiation developed bone metastases 9.5 months after diagnosis and was alive at 19.0 months. The remainder were free of recurrence or progression.ConclusionMTSCC is a rare RCC variant. In this largest series to date, MTSCC presented at a broad range of ages and displayed a female predilection.Imaging and pathologic features of MTSCC display some overlap with papillary RCC.MTSCC is associated with excellent outcomes overall, but is not universally indolent.
    BJU International 11/2014; DOI:10.1111/bju.12992 · 3.13 Impact Factor
  • Mehrad Adibi, Jose A Karam, Christopher G Wood
    European Urology 10/2014; 67(3). DOI:10.1016/j.eururo.2014.10.030 · 12.48 Impact Factor
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    ABSTRACT: Patients with locally advanced renal cell carcinoma (RCC) represent a subset of patients who may benefit from retroperitoneal lymph node dissection (RPLND). We aimed to identify preoperative clinical predictors of positive lymph nodes in patients with RCC without distant metastasis who underwent RPLND.
    The Journal of Urology 10/2014; 193(4). DOI:10.1016/j.juro.2014.10.096 · 3.75 Impact Factor
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    ABSTRACT: OBJECTIVE. The purpose of this study is to evaluate whether intraoperative ultrasound (IOUS) during open partial nephrectomy alters the surgical management for renal cell cancer (RCC). MATERIALS AND METHODS. One hundred ninety-eight consecutive patients undergoing IOUS during open partial nephrectomy for RCC were selected for retrospective review of clinical and imaging data. Patient age and sex, the local extent of the primary lesion, and the presence of additional lesions were recorded. Ultrasound findings were compared with preoperative CT or MRI to determine whether the IOUS findings changed surgical management. Summary statistics were performed to assess what percentage of patients with additional IOUS findings had a change in their surgical management. The Kaplan-Meier method was used to estimate 5-year overall survival (OS) and event-free survival (EFS) rates for all patients. Patients were followed for 9-12 years to assess survival and measure recurrence rates. RESULTS. Twenty-one of 198 patients (10.6%; 95% CI, 6.7-15.8%) had additional findings on IOUS not seen on preoperative imaging. As a result, surgery was modified in 15 of these 21 patients (71.4%; 95% CI, 47.8-88.7%). The 5-year OS rate was 81%, and the EFS rate was 76% for the whole group; most deaths were due to unrelated causes. There was no statistically significant difference in OS (p = 0.867) and EFS (p = 0.069) rates among patients who had a change of management because of additional lesions seen by IOUS. CONCLUSION. IOUS performed during open partial nephrectomy for resection of RCC shows additional findings compared with preoperative cross-sectional imaging that may alter surgical management.
    American Journal of Roentgenology 10/2014; 203(4):822-827. DOI:10.2214/AJR.13.12254 · 2.74 Impact Factor

Publication Stats

5k Citations
1,446.17 Total Impact Points

Institutions

  • 2002–2015
    • University of Texas MD Anderson Cancer Center
      • • Department of Urology
      • • Genitourinary Medical Oncology
      • • Department of Epidemiology
      Houston, Texas, United States
  • 2006–2014
    • University of Houston
      Houston, Texas, United States
  • 2010–2013
    • University of Texas Southwestern Medical Center
      • Department of Urology
      Dallas, Texas, United States
    • Peter MacCallum Cancer Centre
      • Peter MacCallum Cancer Center
      Melbourne, Victoria, Australia
  • 2008–2009
    • Keio University
      Edo, Tōkyō, Japan
  • 2003
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
    • University of California, Davis
      • Department of Urology
      Davis, CA, United States