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European urology 04/2013; 63(4):769. · 7.67 Impact Factor
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Radiological imaging is heavily relied on for follow up after renal ablative therapy. We show that while this is largely reliable, there are quantifiable false negative and false positive findings. A non-involuting zone of ablation should be considered for multisite-directed core biopsies even in the absence of detectable enhancement. OBJECTIVE: To evaluate our experience with radiofrequency ablation (RFA) for renal masses and to report on clinical, radiological and post-RFA biopsy results. PATIENTS AND METHODS: The study collected clinical, radiological and pathological data from 150 consecutive patients who were treated with RFA of a renal mass between 2002 and 2008 at a tertiary referral centre. Post-ablation biopsies were performed in patients with non-involuting lesions or suspicion of recurrence on imaging. Comparisons were performed using the Mann-Whitney U-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Renal malignancy was found in 72.1% of patients based on the initial diagnostic biopsy. Median tumour size was 2.6 cm, 22.7% of patients had a solitary kidney, and most were central tumours. The mean follow-up period was 40.1 month. There was no recurrence in 96.7% of the entire cohort. Cancer-specific survival for 106 patients with sporadic, localized, biopsy proven renal malignancy was 100% at 38.5 months. Biopsies were obtained in 43 patients for a median of 21 months after RFA. Among 38 patients who had biopsy for non-involuting, non-enhancing zones of ablation, three (7.9%) were positive. CONCLUSIONS: Short-term cancer-specific survival after RFA remains excellent and most cases are successful based on a combination of imaging and post-ablation biopsies performed almost 2 years after treatment. There were four out of 150 (2.7%) patients who had recurrences with tissue confirmation; one of these patients was detected on imaging and three (2%) were radiologically occult. The absence of enhancement in the setting of non-involuting lesions is not always a guarantee of a successful ablation.
BJU International 03/2013; · 2.84 Impact Factor
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ABSTRACT: BACKGROUND: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. OBJECTIVE: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. DESIGN, SETTING, AND PARTICIPANTS: In 2006-2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician-patient interaction. Participants had suspected clinical stage T1-T2 disease, were aged ≥18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System-Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. RESULTS AND LIMITATIONS: Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p=0.008); worse cancer-related QOL in physical (p=0.001), psychosocial (p<0.001), and medical (p=0.034) domains; and higher distress (p<0.001). CONCLUSIONS: This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW.
European urology 02/2013; · 7.67 Impact Factor
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ABSTRACT: CONTEXT: There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer. OBJECTIVE: This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer. EVIDENCE ACQUISITION: A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL. EVIDENCE SYNTHESIS: Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes. CONCLUSIONS: Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers.
European urology 09/2012; · 7.67 Impact Factor
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BJU International 05/2012; · 2.84 Impact Factor
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European urology 03/2012; 62(1):136-8; discussion 138-9. · 7.67 Impact Factor
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BJU International 02/2012; 110(6 Pt B):E191. · 2.84 Impact Factor
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European urology 02/2012; 61(5):905-6; discussion 906-7. · 7.67 Impact Factor
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The Journal of urology 12/2011; 187(2):492. · 4.02 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) is considered a relatively rare malignancy worldwide. Around a third of patients with RCC present with metastatic disease, and among those patients treated with nephrectomy with curative intent, more than one-third develop metastases during postoperative follow-up. Due to the absence of curative medical treatments for metastatic RCC, surgery remains the mainstay of therapy. Surgery plays a key role in two aspects: cytoreductive nephrectomy to remove the primary renal tumor in the presence of known metastatic disease, and metastasectomy to remove distant metastatic foci in patients with metastatic RCC.
Hematology/oncology clinics of North America 08/2011; 25(4):753-64. · 2.05 Impact Factor
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ABSTRACT: While laparoscopic adrenalectomy (LA) is considered the standard of care for removal of small adrenal masses, there are minimal data describing the feasibility and outcomes of LA after previous ipsilateral nephrectomy (PIN). The purpose of the study was to describe the perioperative outcomes in a series of patients who were undergoing LA after PIN.
Using an institutional database, we identified patients who underwent LA since 2002 by a single surgeon. Clinical and pathologic data were collected and analyzed. To evaluate outcomes, patients undergoing LA after PIN were compared with patients undergoing LA without PIN.
Of 54 consecutive patients undergoing LA, 8 had PIN for renal-cell carcinoma (RCC). Estimated blood loss was not significantly greater in patients with PIN: 50 mL vs 100 mL, P=0.109. Operative time was longer in patients with PIN: 120 minutes vs 156 minutes, P=0.015. There was no difference in length of hospital stay between groups: Median 2 days for both groups, P=0.635. One patient in the PIN group had a conversion to open adrenalectomy and needed blood transfusion. Perioperative complications were seen in 5/46 (10.6%) patients without and in 1/8 (12.5%) patients with PIN. Surgical margins were negative in all patients.
To the authors' knowledge, this study represents the largest experience with adrenalectomy in the reoperative setting. LA after PIN is associated with a longer operative time. While the potential for conversion is possible, it is technically feasible in selected patients and thus far appears to be associated with similar perioperative outcomes compared with patients without PIN.
Journal of endourology / Endourological Society 08/2011; 25(8):1323-7. · 1.75 Impact Factor
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Jose A Karam,
Sandra Huang,
Jinhai Fan,
Jennifer Stanfield,
Roger A Schultz,
Rey-Chen Pong,
Xiankai Sun,
Ralph P Mason,
Xian-Jin Xie,
Gang Niu,
Xiaoyuan Chen,
Eugene P Frenkel,
Arthur I Sagalowsky,
Jer-Tsong Hsieh
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ABSTRACT: Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24-tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) tissues. Chromosomal analysis and DNA microarray were used to characterize these sublines. Real-time quantitative polymerase chain reaction and immunohistochemistry were used for validation. Epigenetic modifiers were used to study gene regulation. The cell viability was quantified with MTT assay. Chromosomal analysis revealed multiple alterations in metastatic cell lines compared to T24-P. DNA microarray analysis showed that taxol resistance-associated gene (TRAG) 3 was the most upregulated gene. From real-time quantitative polymerase chain reaction and immunohistochemistry, TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation but not histone acetylation. Interestingly, T24-B and T24-L cells were more resistant than T24-P to treatment with antimicrotubule agents such as docetaxel, paclitaxel and vinblastine. TRAG3 mRNA expression was higher in 20% of patients with ≤ pT2 (n = 10) and 60% of patients with ≥ pT3 (n = 20) compared to normal adjacent tissue (p = 0.05). In addition, the median TRAG3 expression was 6.7-fold higher in ≥ pT3 tumors compared to ≤ pT2 tumors. Knowing the status of TRAG3 expression could help clinicians tailor treatment to a particular patient population that could benefit from treatment, while allocating patients with resistant tumors to new experimental therapies.
International Journal of Cancer 06/2011; 128(12):2823-32. · 5.44 Impact Factor
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ABSTRACT: While surgical excision remains the gold standard for curative treatment of small renal cell carcinomas, ablative therapy has a place as a minimally invasive, kidney function-preserving therapy in carefully selected patients who are poor candidates for surgery. Although laparoscopic cryoablation and percutaneous radiofrequency ablation (RFA) are commonly performed, percutaneous cryoablation and laparoscopic RFA are reportedly being performed with increasing frequency. The renal function and complication profiles following ablative therapy are favorable, while oncologic outcomes lag behind those of surgery, thus reinforcing the need for careful patient selection.
Surgical Oncology Clinics of North America 04/2011; 20(2):341-53, viii. · 1.12 Impact Factor
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Jose A Karam
BJU International 03/2011; 108(4):537-8. · 2.84 Impact Factor
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ABSTRACT: • To assess the cost-effectiveness of using cytological evaluation, NMP22 BladderChek®, and fluorescence in situ hybridization (FISH) UroVysion® in addition to cystoscopy in patients with a history of bladder cancer undergoing surveillance for recurrence.
• In all, 200 consecutive patients with a history of bladder cancer not invading the muscle were prospectively enrolled at The University of Texas MD Anderson Cancer Center. • Five surveillance strategies were compared: (i) cystoscopy alone; (ii) cystoscopy and NMP22; (iii) cystoscopy and FISH; (iv) cystoscopy and cytology; and (v) cystoscopy and positive NMP22 confirmed by positive FISH. • The cost per cancer detected was calculated. • For patients with an initial positive test and negative cystoscopy, tumour detected at first follow-up was assumed to be too small to be visualized at the initial assessment and the biomarker was credited with early detection.
• Cancer was detected in 13 patients at study entry. • Detection rates for the five surveillance strategies were: (i) 52%, (ii) 56%, (iii) 72%, (iv) 60%, and (v) 56%. • The costs per tumour detected (at the time of initial marker analysis) were (i) $7692; (ii) $12,000; (iii) $26,462; (iv) $11,846; and (v) $10,292. • When early detection of biomarkers was factored in, the CPTD became: (i) $7692; (ii) $11,143; (iii) $19,111; (iv) $10,267; and (v) $9557. • There were 12 new cancers detected at first follow-up (median time, 4.1 months). None of the tumours detected by biomarkers but not by cystoscopy were invasive.
• Cystoscopy alone remains the most cost-effective strategy to detect recurrence of bladder cancer not invading the muscle. • The addition of urinary markers adds to cost, without improved detection of invasive disease.
BJU International 03/2011; 108(7):1119-23. · 2.84 Impact Factor
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European urology 02/2011; 59(4):541-2. · 7.67 Impact Factor
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Jose A Karam,
Brian I Rini,
Leticia Varella,
Jorge A Garcia,
Robert Dreicer,
Toni K Choueiri,
Eric Jonasch,
Surena F Matin,
Steven C Campbell,
Christopher G Wood,
Nizar M Tannir
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ABSTRACT: Metastasectomy is often incorporated in overall treatment in patients with metastatic renal cell carcinoma. While this approach was studied in the immunotherapy era, only a few cases have been described in the targeted therapy era. Thus, we evaluated the role of metastasectomy in patients with metastatic renal cell carcinoma who received prior targeted therapy.
We retrospectively evaluated the records of patients who underwent consolidative metastasectomy after targeted therapy at 3 institutions from 2004 to 2009. All patients received at least 1 cycle of targeted therapy before surgical resection of all visible disease.
We identified 22 patients. Metastasectomy sites included the retroperitoneum in 12 patients, lung in 6, adrenal gland in 2, bowel in 2, and mediastinum, bone, brain and inferior venal caval thrombus in 1 each. A total of 6 postoperative complications were observed in 4 patients within 12 weeks after surgery, which resolved with appropriate management. Postoperatively 9 patients received at least 1 targeted therapy. In 11 patients recurrence developed a median of 42 weeks after metastasectomy and another 11 experienced no recurrence at a median of 43 weeks. At a median followup of 109 weeks 21 patients were alive and 1 died of renal cell carcinoma 105 weeks after metastasectomy.
In a cohort of select patients with a limited tumor burden after treatment with targeted agents consolidative metastasectomy is feasible with acceptable morbidity. Significant time off targeted therapy and long-term tumor-free status are possible with this approach.
The Journal of urology 02/2011; 185(2):439-44. · 4.02 Impact Factor
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Nicholas G Cost,
Scott E Delacroix,
Joshua P Sleeper,
Paul J Smith,
Ramy F Youssef,
Brian F Chapin, Jose A Karam,
Stephen Culp,
E Jason Abel,
James Brugarolas,
Ganesh V Raj,
Arthur I Sagalowsky,
Christopher G Wood,
Vitaly Margulis
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ABSTRACT: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases.
To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi.
A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi.
The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT.
Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction.
TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.
European urology 02/2011; 59(6):912-8. · 7.67 Impact Factor
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ABSTRACT: Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.
To establish and characterize a panel of mouse models of renal cell carcinoma (RCC) derived from patients undergoing radical nephrectomy.
In vivo and in vitro animal experiments.
Tumor tissues obtained during surgery were implanted into the subcutaneous space of female BALB/c nude mice and serially passaged into new mice. Tumors were characterized by histology, short tandem repeat (STR) fingerprinting, von Hippel-Lindau (VHL) gene sequencing, and single nucleotide polymorphism (SNP) analysis. Tumor-bearing mice were treated with sunitinib or everolimus. Primary cell cultures were derived from patient tumors and transfected with a lentivirus carrying the luciferase gene. Four subcutaneous xenograft mouse models were developed, representing papillary type 1, papillary type 2, clear cell, and clear cell with sarcomatoid features RCC.
RCC mouse models were established from four patients with distinct histologies of RCC. Tumor growth was dependent on histologic type, the size of the implanted tumor chip, and the passage number. Mouse tumors accurately represented their respective original patient tumors, as STR fingerprints were matching, histology was comparable, and SNP profiles and VHL mutation status were conserved with multiple passages. Bioluminescence imaging results were commensurate with subcutaneous xenograft growth patterns. Mice treated with sunitinib and everolimus exhibited an initial response, followed by a later stage of resistance to these agents, which mimics the clinical observations in patients with RCC.
We developed four mouse xenograft models of RCC with clear-cell and papillary histologies, with stable histologic and molecular characteristics. These models can be used to understand the basic biology of RCC as well as response and resistance to therapy.
European urology 12/2010; 59(4):619-28. · 7.67 Impact Factor
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ABSTRACT: We retrospectively evaluated the feasibility, safety and outcomes of radio frequency ablation of primary renal tumors to control local disease while preserving renal parenchyma in a series of patients with metastatic renal cell carcinoma in a single institutional, multidisciplinary setting.
We evaluated the records of patients with metastatic renal cell carcinoma who underwent percutaneous radio frequency ablation of a primary renal tumor. Patient demographic and disease characteristics, adjunctive medical and surgical therapies, recurrence and clinical outcomes were studied.
A total of 15 patients treated between 2002 and 2008 met study inclusion criteria. There was no incomplete ablation or local recurrence. Ten patients had biopsy proven renal cell carcinoma in the ablated renal mass. Eight patients had a solitary metastasis, 3 had metastasis at 2 sites and 4 had 3 or more metastatic sites. Four patients experienced major complications. Median radiographic and clinical followup in patients at risk for an event was 25.5 and 33.0 months, respectively. The overall survival rate 1, 3 and 5 years after radio frequency ablation was 73.3%, 57.1% and 38.1%, respectively. At last evaluation 4 patients were in complete remission, 4 had no evidence of local recurrence but had evidence of distant disease and 7 had died of the disease.
Radio frequency ablation is feasible and safe in highly selected patients with metastatic renal cell carcinoma, resulting in durable local control as part of multimodality management and achieving renal preservation. Further investigation is required to define the role of radio frequency ablation in this patient population.
The Journal of urology 11/2010; 184(5):1882-7. · 4.02 Impact Factor
