Christopher G Wood

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

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Publications (229)1130.36 Total impact

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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; · 3.05 Impact Factor
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    ABSTRACT: Ewing sarcoma family of tumors (ESFT) of the kidney are exceedingly rare. Given the rarity of this neoplasm and the complexity associated with its management, information regarding treatment and outcome is warranted.
    American journal of clinical oncology. 09/2014;
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    ABSTRACT: Dietary factors may affect risk of renal cell carcinoma (RCC). In an ongoing case-control study of RCC initiated in Houston, Texas, in 2002, we identified 3 empirically derived dietary patterns: "fruits and vegetables," "American/Western," and "Tex-Mex." Among 659 RCC cases and 699 controls, we evaluated associations of these dietary patterns with RCC risk and whether the associations varied by obesity status, smoking status, physical activity level, history of hypertension, and genetic variants previously identified via genome-wide association studies. Among persons in the highest categories of adherence versus the lowest, the "fruits and vegetables" dietary pattern was associated with an approximately 50% lower RCC risk (Ptrend < 0.001), while "American/Western" dietary pattern scores were positively associated with a 2-fold higher risk (Ptrend < 0.001). We observed synergistic interaction between the American/Western pattern and hypertension status: The odds ratio (highest tertile vs. lowest) among persons with hypertension was 2.23 (95% confidence interval: 1.43, 3.45), as compared with 1.76 (95% confidence interval: 1.16, 2.70) among persons without hypertension (additive Pinteraction = 0.01). A variant (rs718314) in the inositol 1,4,5-trisphosphate receptor, type 2 gene (ITPR2) was found to interact with the American/Western dietary pattern in relation to RCC risk (additive Pinteraction = 0.03). ITPR2 has been shown to affect nutrient metabolism and central obesity. Dietary patterns, genetic variants, and host characteristics may individually and jointly influence susceptibility to RCC.
    American journal of epidemiology. 07/2014;
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    ABSTRACT: Purpose: MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of kidney cancer. Its incidence and the genome-wide characterization of its genetic origin have not been fully elucidated. Experimental design: We performed RNA and exome sequencing on an exploratory set of TRCC (n=7), and validated our findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n=460). Results: Using the TCGA dataset, we identified 7 TRCC (1.5%) cases and determined their genomic profile. We discovered three novel partners of MITF/TFE (LUC7L3, KHSRP and KHDRBS2), which are involved in RNA splicing. TRCC displayed a unique gene expression signature as compared to other RCC types, and showed activation of MITF, the transforming growth factor β1 and the PI3K complex targets. Genes differentially spliced between TRCC and other RCC types were enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct mutational spectrum as compared to ccRCC, with frequent mutations in chromatin remodeling genes (six of eight cases, three of which from the TCGA). In two cases, we identified mutations in INO80D, an ATP-dependent chromatin remodeling gene, previously shown to control the amplitude of the S phase. Knockdown of INO80D decreased cell proliferation in a novel cell line bearing LUC7L3-TFE3 translocation. Conclusions: This genome-wide study defines the incidence of TRCC within a ccRCC-directed project and expands the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin remodeling genes.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2014;
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    Riaz J. Karmali, Hiroo Suami, Christopher G. Wood, Jose A. Karam
    BJU International 05/2014; · 3.05 Impact Factor
  • Dae Y Kim, Jose A Karam, Christopher G Wood
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    ABSTRACT: Numerous biological pathways are affected in renal cell carcinoma and the introduction of targeted agents has improved the survival of patients with advanced and metastatic disease. Durable and long-lasting cure is rarely achieved, and in select cases, the excision of metastatic deposits has shown to increase survival. Clinical trials of targeted agents are being explored as neoadjuvant and adjuvant therapies with the role of metastasectomy evolving in the treatment paradigm. This review examines published reports of metastasectomy and its developing role in the era of targeted therapy. A Medline search was conducted using keywords "metastasectomy," "renal cell carcinoma," and "targeted therapy," and selected articles are discussed by examining prognostic stratification and metastasectomy in major anatomic regions. Most published reports span earlier periods of immunotherapy and chemotherapy, and henceforth, discussions are in historical context in this review. Although there is lack of Level 1 evidence, reports have suggested the prognostic value and survival benefit for metastasectomy in lesions that are amenable to complete resection after longer disease-free intervals in carefully selected patients with adequate performance status. Therefore, the role of metastasectomy must be further elucidated in the era of targeted therapy.
    World Journal of Urology 04/2014; · 2.89 Impact Factor
  • Stephen H Culp, Jose A Karam, Christopher G Wood
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    ABSTRACT: Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort. Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death. A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T3), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001). Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.
    Urologic Oncology 04/2014; · 3.65 Impact Factor
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    ABSTRACT: Supra-hepatic IVC tumor thrombus in RCC has historically portended a poor prognosis. With advances in perioperative management of patients with high level thrombi, contemporary outcomes are hypothesized to be improved. We evaluated long-term oncologic outcomes of contemporary surgical management of RCC patients with level III-IV IVC thrombi treated at high volume centers. Clinical and pathologic data of RCC patients with level III-IV thrombus who had surgery from January 2000-June 2013 at 4 tertiary referral centers was examined. Survival outcomes and associated prognostic variables were assessed with Kaplan-Meier and multivariable Cox-regression analyses. 166 patients were identified (69 with level III, and 97 with level IV thrombus). Median post-operative follow-up was 27.8 months. Patients with no evidence of nodal or distant metastases (pN0/X,M0) had 5-yr CSS and OS of 49.0% and 42.2% respectively. There were no differences in survival based on the level of tumor thrombus or pathologic tumor stage. Variables associated with increased risk of death from kidney cancer on multivariable analysis were: regional nodal metastases (HR 3.94,p<0.0001), systemic metastases (HR 2.39,p=0.01), tumor grade 4 (HR 2.25,p=0.02), histologic tissue necrosis (HR 3.11,p=0.004), and elevated pre-operative serum alkaline phosphatase level (HR 2.30, p=0.006). Contemporary surgical management achieves nearly 50% 5-year survival in non-metastatic patients with RCC tumor thrombus above the hepatic veins. Factors associated with increased mortality included nodal/distant metastases, advanced grade, histologic necrosis and elevated pre-operative serum alkaline phosphatase. These findings support an aggressive surgical approach to the management of RCC patients with advanced tumor thrombi.
    The Journal of urology 04/2014; · 3.75 Impact Factor
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    ABSTRACT: Background Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective and heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery. Objective To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). Design, setting, and participants This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. Intervention Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patient underwent partial or radical nephrectomy after axitinib therapy. Outcome measurements and statistical analysis The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST). Results and limitations A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers. Conclusions Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC. Patient summary In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use. Trial registration This clinical trial was registered with clinicaltrials.gov (NCT01263769).
    European Urology 04/2014; · 10.48 Impact Factor
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    ABSTRACT: Objectives● To evaluate the feasibility, safety, pathologic, radiologic and functional outcomes of salvage surgery after prior renal mass ablation therapy.Patients and Methods● After IRB approval, we reviewed our renal tumor database, and described characteristics and outcomes of patients who experienced a local recurrence after energy ablation for renal masses, and underwent salvage surgical therapy.Results● Fourteen patients fit the inclusion criteria. Median age was 65 years (IQR 59-77), with median Charlson Comorbidity Index of 2 (IQR 0.75-3.00). Three patients had solitary kidney. Seven patients received their ablation therapies at an outside institution. Ten patients previously underwent percutaneous RFA, 3 percutaneous cryoablation, and 1 laparoscopic cryoablation. Median nephrometry score at time of surgery was 7 (IQR 5-9). Time from ablation to surgery was 26.5 months (IQR 16.3-39.3). ● Eleven patients underwent partial nephrectomy, and 3 underwent planned radical nephrectomy. Median surgery time was 203 minutes (IQR 177-265). Median length of stay was 5.5 days. There was 1 microscopic positive surgical margin. Median tumor size at final pathology was 3.1 cm. Thirteen patients had RCC and 1 had no tumor present. Nine were pT1a, 1 pT1b, 2 pT3a, and 1 pT3b. ● There were 4 Clavien grade 3 complications in 4 patients. ● Median preoperative eGFR and eGFR at last follow-up were 66 and 66 mL/min/1.73 m2. ● There were no deaths at median follow-up of 26.5 months (IQR 10.5-49.5).Conclusions● Patients with prior renal ablation therapy can be salvaged with partial or radical nephrectomy with good intermediate-term outcomes. ● These procedures may be associated with a high rate of adverse events. ● Longer follow-up is necessary.
    BJU International 03/2014; · 3.05 Impact Factor
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    ABSTRACT: Surgical resection of renal cell carcinoma (RCC) is the benchmark for long-term cure of the disease. Although open or laparoscopic radical nephrectomy is considered the gold standard for stage T1b-T4 tumors, nephron-sparing surgery is the preferred operative modality for small renal masses demonstrating equivalent oncologic efficacy and improved renal function outcomes compared with complete nephrectomy. With the advance of minimally invasive surgery, nephron-sparing procedures can safely be conducted laparoscopically with or without robotic assistance. RCC with intravenous tumor thrombus presents a surgical challenge, but multidisciplinary surgical approaches can provide long-term benefit in these patients. The role of cytoreductive nephrectomy and metastasectomy in patients with metastatic RCC (mRCC) is controversial, but seems to be beneficial for patients in the era of targeted therapy.
    Seminars in Interventional Radiology 03/2014; 31(1):27-32.
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    ABSTRACT: BACKGROUND High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with uniformly poor survival. Neoadjuvant chemotherapy may offer a way to improve clinical outcomes. The authors compared the survival rates of patients with UTUC who received neoadjuvant chemotherapy before surgery with the rates among patients who did not.METHODSA retrospective review was conducted of patients with high-risk UTUC who received neoadjuvant chemotherapy followed by surgery from 2004 to 2008 (study group) compared with a matched cohort who underwent initial surgery from 1993 to 2003 (control group). Fisher exact tests, Wilcoxon rank-sum tests, and Kaplan-Meier methods were used. The log-rank test and Cox proportional-hazards models were used to evaluate the association of the 2 outcomes with patient, treatment, and tumor characteristics in univariate and multivariate models.RESULTSOf 112 patients, there were 31 in the study group and 81 in the control group. Patients who received neoadjuvant chemotherapy had improved overall survival (OS) and disease-specific survival (DSS) with a 5-year DSS rate of 90.1% and a 5-year OS rate of 80.2% versus DSS and OS rates of 57.6% for those who underwent initial surgery (P = .0204 and P = .0015, respectively). In multivariate analyses, the neoadjuvant group had a lower risk of mortality (OS: hazard ratio, 0.42 [P = .035]; DSS: hazard ratio, 0.19 [P = .006]).CONCLUSIONS Neoadjuvant chemotherapy improved the survival of patients with UTUC compared with a matched historic cohort of patients who underwent initial surgery. Patients with high-risk UTUC should be considered for neoadjuvant chemotherapy in view of the limited opportunity to administer effective cisplatin-based chemotherapy after nephroureterectomy. Cancer 2014. © 2014 American Cancer Society.
    Cancer 03/2014; · 5.20 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 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Purpose: Cytoreductive nephrectomy (CN) remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma (mRCC). Although the role of partial nephrectomy (PN) is well accepted in patients with localized disease, limited data are available regarding PN in the metastatic setting. We sought to identify the indications and outcomes for PN in the setting of mRCC with particular attention to different PN subgroups. Materials and Methods: We analyzed data from a consecutive cohort of 33 patients with mRCC who underwent PN at a single institution between 1996 and 2011. Non-parametric statistics were used to compare PN subgroups. Overall survival (OS) was estimated using Kaplan-Meier method, and survival functions were compared using the log-rank test. Results: Eight patients presented with bilateral synchronous renal masses; 20 with a metachronous contralateral renal mass; and 5 with a unilateral renal mass. Overall, 22 patients (67%) died of disease at a median of 27 months after PN. Patients who underwent PN for a metachronous contralateral renal mass and for a renal mass ≤4cm had the best OS (61 months and 42 months, respectively). Median OS for patients with and without metastatic disease at original diagnosis was 27 and 63 months, respectively (p=0.003). Conclusions: Our findings suggest that the presence of metastasis at original diagnosis and the timing of presentation of the PN index lesion play an important role in survival. These factors should be taken into consideration when determining which patients would benefit from partial nephrectomy in the setting of mRCC.
    The Journal of urology 01/2014; · 3.75 Impact Factor
  • Stephen H. Culp, Jose A. Karam, Christopher G. Wood
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    ABSTRACT: Objectives Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort. Materials and methods Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death. Results A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T3), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7 cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001). Conclusions Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.
    Urologic Oncology: Seminars and Original Investigations. 01/2014;
  • Dae Y Kim, Christopher G Wood, Jose A Karam
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    ABSTRACT: The incidental renal mass represents a heterogeneous group that contains both benign and malignant pathologies. The majority of renal cell carcinomas are discovered incidentally, without the presence of symptoms directly related to the mass, and are closely associated with the term small renal masses because of the discovery before the onset of symptoms. In general, small renal masses are defined as 4 cm or smaller, and may account for greater than half of renal cell carcinoma diagnosis. The use of renal mass biopsy may offer additional pathological information but the clinician must be reminded of the technical and diagnostic limitations of renal mass biopsy. Patient-dependent factors, such as life expectancy and comorbidities, guide the management of small renal masses, which include active surveillance, partial nephrectomy, radical nephrectomy, and ablative techniques (cryoablation and radiofrequency ablation). Partial nephrectomy has demonstrated durable oncologic control for small renal masses while preserving renal function and, if feasible, is the current treatment of choice. In the other extreme of the renal cell carcinomas spectrum and in the presence of metastatic disease, the removal of the renal primary tumor is termed cytoreductive nephrectomy. Two randomized trials (SWOG 8949 and EORTC 30947) have demonstrated a survival benefit with cytoreductive nephrectomy before the initiation of immunotherapy. These two studies have also been the motivation to perform cytoreductive nephrectomy in the targeted therapy era. Currently, there are two ongoing randomized prospective trials accruing to investigate the timing and relevance of cytoreductive nephrectomy in the contemporary setting of targeted therapy.
    American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting. 01/2014; 34:e214-21.
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    ABSTRACT: Upper tract urothelial carcinoma (UTUC) is a clinically heterogeneous disease that lacks high-quality trials that provide definitive prognostic markers. Insulin-like growth factor messenger RNA binding protein 3 (IMP3) has been associated with outcomes in urothelial carcinoma of the bladder but was not yet studied in UTUC. To evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU). We investigated the expression of IMP3 and its association with clinical outcomes using tissue microarrays constructed from 622 patients treated with RNU at seven international institutions between 1991 and 2008. All patients were diagnosed with UTUC and underwent RNU. Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality. IMP3 was expressed in 12.2% of patients with UTUC (n=76). The expression was tumor specific and correlated with higher stages/grades. Within a median follow-up of 27 mo (interquartile range [IQR]: 12-53), 191 patients (25.4%) experienced disease recurrence, and 165 (21.9%) died of the disease. Patients with IMP3 demonstrated significantly worse recurrence-free survival (27.4% vs 75.1%; p<0.01), cancer-specific survival (34.5% vs 78.9%; p<0.01), and overall survival (15.6% vs 64.8%; p<0.01) at 5 yr compared with those without IMP3. In multivariable Cox regression analyses, which adjusted for the effects of standard clinicopathologic features, IMP3expression was independently associated with disease recurrence (hazard ratio [HR]: 1.87; p<0.01), cancer-specific mortality (HR: 2.15; p<0.01), and all-cause mortality (HR: 2.07; p<0.01). Major limitations include the retrospective design and relatively short follow-up time. IMP3 expression is independently associated with disease recurrence, cancer-specific mortality, and all-cause mortality in UTUC. IMP3 may help improve risk stratification and prognostication of UTUC patients treated with RNU.
    European Urology 12/2013; · 10.48 Impact Factor
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    ABSTRACT: We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
    Cancer Cell. 12/2013; 26(3):319-330.
  • Tin C Ngo, Christopher G Wood, Jose A Karam
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    ABSTRACT: The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease.
    Urologic Oncology 11/2013; · 3.65 Impact Factor
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    ABSTRACT: Surgery for renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus above the hepatic veins is technically complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with poor outcomes. To determine the preoperative predictors of major complications and 90-d mortality after surgery in RCC patients who have IVC thrombus above the hepatic veins. We reviewed medical records of all RCC patients who had IVC tumor thrombus above hepatic veins and had had surgery between January 2000 and December 2012 at the Mayo Clinic, M.D. Anderson Cancer Center, University of Texas Southwestern Medical Center, and the University of Wisconsin Hospital. Major complications recorded were defined as ≥3A according to the Clavien-Dindo system within 90 d of surgery. Univariate and multivariate analyses were used to evaluate associations of preoperative variables with risk of major complications or 90-d mortality. A total of 162 patients were identified for study (level 3, 4 in 69, 93 patients, respectively, according to the Neves classification). Cardiopulmonary bypass was used in 60 of 162 patients (37.5%), and 40 patients (24.7%) had preoperative angioembolization. Major complications were reported in 55 patients (34.0%), with the most common being respiratory, cardiac, and hematologic issues. After multivariate analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with increased risk of major complications. Mortality was reported in 17 patients (10.5%) within 90 d after surgery. After multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and low serum albumin were preoperative factors independently associated with increased risk of 90-d mortality. Contemporary perioperative mortality and major complication rates for RCC patients who have upper-level thrombus are 10% and 34%, respectively. Patients who have ECOG PS >1 or low serum albumin have increased risk for perioperative mortality.
    European Urology 11/2013; · 10.48 Impact Factor

Publication Stats

4k Citations
1,130.36 Total Impact Points

Institutions

  • 2002–2014
    • University of Texas MD Anderson Cancer Center
      • • Department of Urology
      • • Genitourinary Medical Oncology
      • • Department of Epidemiology
      Houston, Texas, United States
  • 2013
    • National Institutes of Health
      • Branch of Urologic Oncology
      Bethesda, MD, United States
    • Texas A&M University System Health Science Center
      • Molecular and Cellular Medicine
      Bryan, Texas, United States
    • Columbia University
      • Department of Urology
      New York City, NY, United States
  • 2010–2013
    • University of Wisconsin, Madison
      • Department of Urology
      Madison, MS, United States
    • Netherlands Cancer Institute
      • Department of Urology
      Amsterdamo, North Holland, Netherlands
  • 2009–2013
    • University of Texas Southwestern Medical Center
      • Department of Urology
      Dallas, TX, United States
    • National University of Singapore
      • Department of Surgery
      Singapore, Singapore
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
    • General University Hospital of Larissa
      Lárissa, Thessaly, Greece
  • 2012
    • Weill Cornell Medical College
      • Department of Urology
      New York City, New York, United States
  • 2011
    • Kitasato University
      • Department of Urology
      Edo, Tōkyō, Japan
  • 2009–2011
    • New York Presbyterian Hospital
      New York City, New York, United States
  • 2006–2009
    • University of Texas Health Science Center at Houston
      • Division of Urology
      Houston, TX, United States
  • 2008
    • Medical University of Vienna
      • Department of Urology
      Wien, Vienna, Austria
    • Keio University
      Edo, Tōkyō, Japan
  • 2007
    • McGill University
      • Division of Urology
      Montréal, Quebec, Canada
  • 2003
    • University of Texas Medical Branch at Galveston
      • Department of Internal Medicine
      Galveston, TX, United States
    • University of California, Davis
      • Department of Urology
      Davis, CA, United States