Stephen B Riggs

University of California, Los Angeles, Los Angeles, CA, United States

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Publications (15)61.19 Total impact

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    ABSTRACT: We examined outcomes after partial nephrectomy in patients with tumors in a solitary kidney to determine the extent to which patient, surgery and tumor specific variables influenced the glomerular filtration rate and local recurrence postoperatively. Demographics, renal function, comorbidities, renal cell carcinoma history, and operative and pathological data were recorded. The effect on changes in early and late postoperative glomerular filtration rate and local recurrence were analyzed. In 84 patients undergoing a total of 89 partial nephrectomies the mean immediate postoperative decrease in the glomerular filtration rate in those with no ischemia, warm ischemia (mean 12 minutes) and cold ischemia (mean 33 minutes) was 29%, 37% and 45%, respectively (p <0.01). Late glomerular filtration rate decreases were 12%, 6% and 16%, respectively (p = 0.17). Cold ischemia and multiple vascular risk factors were associated with immediate glomerular filtration rate decreases (p = 0.008 and 0.04, respectively). Local recurrence, which developed in 13 patients (18%), was associated with positive margins and T stage (p = 0.01 and 0.02, respectively). End stage renal disease developed in 3 patients (4%) and an additional 5 (6%) required nephrectomy for local recurrence. Partial nephrectomy generally results in a small decrease in the glomerular filtration rate, and limited warm and cold ischemia does not appear to adversely affect long-term renal function. Positive margins and T stage greater than 2 are the most important predictors of local recurrence in a solitary kidney. They pose a significant risk to end stage renal disease-free survival due to the need for completion nephrectomy in many of these patients. Partial nephrectomy should be considered the standard of care in all patients with tumor in the solitary kidney.
    The Journal of urology 03/2009; 181(5):2037-42; discussion 2043. · 3.75 Impact Factor
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    ABSTRACT: To identify the molecular signature of localized (N0M0) clear cell renal cell carcinoma (RCC) and assess its ability to predict outcome. Clinical characteristics and pathologic records of 170 patients with localized clear cell RCC who underwent nephrectomy were reviewed. Immunohistochemical analysis was done on a tissue microarray of all primary tumors using a kidney cancer-related panel of protein markers, which included CAIX, CAXII, CXCR3, gelsolin, Ki-67, vimentin, EpCAM, p21, p27, p53, pS6, PTEN, HIF-1alpha, pAkt, VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3. Associations with disease-free survival (DFS) were evaluated with Cox models, and a concordance index assessed prognostic accuracy. Median follow-up was 7.1 years. The final multivariate Cox model determined T classification, Eastern Cooperative Oncology Group performance status, and five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) to be independent prognostic indicators of DFS. The molecular signature based on these markers predicted DFS with an accuracy of 0.838, an improvement over T classification of 0.746, and the University of California-Los Angeles Integrated Staging System of 0.780. A constructed nomogram combined the molecular, clinical, and pathologic factors and approached a concordance index of 0.904. A molecular signature consisting of five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) can predict DFS for localized clear cell RCC. The prognostic ability of the signature and nomogram may be superior to clinical and pathologic factors alone and may identify a subset of localized patients with aggressive clinical behavior. Independent, external validation of the nomogram is required.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2009; 18(3):894-900. · 4.56 Impact Factor
  • Journal of Urology - J UROL. 01/2009; 181(4):438-438.
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    ABSTRACT: The management of renal cell carcinoma (RCC) is evolving toward less extirpative surgery and the use of targeted therapy. The authors set out to provide a benchmark against which emerging therapies should be measured. A prospective database including clinical and pathological variables for 1632 patients with RCC treated between 1989 and 2005 was queried. Patients were stratified using the University of California-Los Angeles Integrated Staging System (UISS) into low-, intermediate-, and high-risk groups. Disease-specific survival (DSS) was measured. Response to systemic therapy for patients with advanced disease was assessed. Nephrectomy was performed in 1492 patients. Overall 5-, 10-, and 15-year DSS was 55%, 40%, and 29%. For localized disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 97% and 92%, 81% and 61%, and 62% and 41%, respectively. For metastatic disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 41% and 31%, 18% and 7%, and 8% and 0%, respectively. Patients with metastatic disease receiving immunotherapy (n=453) had complete response in 7% (median survival [MS], 120+ months), partial response in 15% (MS, 42.8 months), stable disease in 33% (MS, 38.6 months), and progressive disease in 45% (MS, 11.6 months). Most patients with localized RCC do well with surgery alone, but effective adjuvant therapy is needed for patients identified as at high risk for recurrence. For advanced disease, newer targeted and potentially less toxic treatments should be at least as effective as those achieved with aggressive surgical resection and immunotherapy.
    Cancer 10/2008; 113(9):2457-63. · 5.20 Impact Factor
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    ABSTRACT: An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2/3 can quantify cancer patients' well being and may be used to select patients for treatment. The objective of the current study was to investigate the outcomes of cytoreductive nephrectomy (CN) for patients who have an impaired performance status (ECOG PS 2/3). Patients who underwent CN for renal cell carcinoma (RCC) between 1989 and 2006 were identified. Patient records were reviewed for age, symptoms, ECOG PS, tumor size, stage, grade, histology, sarcomatoid features, lymph node metastasis, site of metastasis, and the presence of bone metastases (BM) in weight-bearing structures. The relation of ECOG PS to outcome variables was evaluated. Four hundred eighteen patients underwent CN, including 117 patients who had an ECOG PS of 0, 274 patients who had an ECOG PS of 1, and 27 patients who had an ECOG PS of 2/3. Patients who had a worse ECOG PS were younger, had higher tumor classification and grade, and more frequently demonstrated anemia and BM. Only 37.5% of patients who had an ECOG PS of 2/3 experienced an improvement in performance in the postoperative period, and only 57.5% went on to receive systemic therapy, of whom none attained an objective responses. The median disease-specific survival for patients who had an ECOG PS of 0, 1, and 2/3 was 27 months, 13.8 months, and 6.6 months, respectively (P<.001). Patients who had an ECOG PS of 2/3 could be stratified further by the presence or absence of BM into 2 groups (median disease-specific survival: 17.7 months and 2.1 months, respectively; P = .006). Surgery in patients who have a poor performance may serve a palliative function but should be performed with caution because of the poor outcome of such patients. ECOG PS is influenced strongly by BM. A subset of patients with an ECOG PS of 2/3 that are symptomatic specifically from BM may derive greater benefit from CN than patients who hare symptomatic because of visceral metastases.
    Cancer 09/2008; 113(6):1324-31. · 5.20 Impact Factor
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    ABSTRACT: Patients with renal cell carcinoma brain metastases (RCCBM) are frequently excluded from trials and to the authors' knowledge no guidelines currently exist regarding central nervous system (CNS) surveillance or treatment. The objective of the current study was to assist in the creation of treatment guidelines. Patients undergoing evaluation for RCCBM from 1989 to 2006 were identified. Their characteristics, symptoms, pathologic variables, number and size of RCCBM, CNS treatment, CNS recurrence, overall survival, and use of systemic therapy were reviewed. A total of 138 patients were identified with RCCBM, of whom 92% had clear cell RCC and 95% had synchronous extracranial metastases. CNS symptoms were noted in 67% of patients. Symptomatic CNS tumors were larger (2.1 cm vs 1.3 cm; P < .001) and more frequently required a craniotomy (P < .001). The median overall survival after a diagnosis of RCCBM was 10.7 months; the 1-year, 2-year, and 5-year survival rates were 48%, 30%, and 12%, respectively. Median CNS recurrence was 9 months after RCCBM treatment. The initial number of tumors (>1 tumor) was found to be an independent predictor of CNS recurrence (hazards ratio of 3.72; P < .001). Those patients with 1 and >1 lesion had a median CNS recurrence-free survival of 13 months and 4 months, respectively (P < .001). Patients receiving interleukin-2 after CNS treatment had a response rate of 17%. Patients with metastatic RCC should undergo CNS screening to allow the identification of smaller lesions that are more amenable to treatment. Those patients with solitary RCCBM are less likely to develop CNS recurrence after local therapy. Selected patients with good performance status may exhibit prolonged survival and should be offered aggressive therapy.
    Cancer 07/2008; 113(7):1641-8. · 5.20 Impact Factor
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    ABSTRACT: We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p = 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.
    The Journal of urology 06/2008; 179(5):1719-26. · 3.75 Impact Factor
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    ABSTRACT: To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise. The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy. Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney. The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic-based strategies. This might be a signal for urological surgeons to re-evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting.
    BJU International 05/2008; 102(6):692-6. · 3.05 Impact Factor
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    ABSTRACT: The treatment of small renal tumors continues to evolve in parallel with advances in ablative technology. We compared the lesion geometry of 3, 17 gauge cryoneedles to determine the most effective distance and configuration of the cryoneedles in an in vivo porcine kidney model. Argon gas based renal cryoablation was performed in 6 pigs using a laparoscopically assisted percutaneous approach. Cryoablation using a single cryoneedle and a template of 3 cryoneedles with various ice ball shapes, including elliptical, bulb-shaped and standard 17 gauge cryoneedles (Galil Medical, Plymouth Meadow, Pennsylvania) was performed in 3 pigs. Three additional pigs underwent renal cryoablation using elliptical cryoneedles in 3 triangular template configurations with the cryoneedles spaced 1, 1.5 and 2 cm apart, respectively. The animals were sacrificed a minimum of 2 weeks following treatment. Elliptical cryoneedles achieved the largest area of necrosis when used in single and template configurations. When used in a template configuration of 3 needles 1, 1.5 and 2 cm apart from each other the calculated volume of necrosis was 4.3 x 4.5 x 2.5, 4.9 x 4.1 x 2.5 and 4.0 x 4.5 x 2.5 cm, respectively. Using a single 17 gauge cryoneedle is inadequate for treating most small renal tumors. Cryoneedles with an elliptical ice ball are most effective for achieving consistent and reliable tissue destruction. The 1.5 cm template configuration generated the largest area of necrosis. Our data suggest that with the current technology renal cryoablation should be limited to lesions not greater than 4 cm.
    The Journal of urology 02/2008; 179(1):333-7. · 3.75 Impact Factor
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    ABSTRACT: Through its binding with interferon inducible angiostatic chemokines the chemokine receptor CXCR3 has an important role in regulating tumor mediating immunity, angiogenesis and metastatic spread. To evaluate its role in the biology of clear cell renal cell carcinoma we performed a tissue microarray based study. The tissue microarray comprised 154 patients who underwent nephrectomy for localized (N0M0) clear cell renal cell carcinoma at UCLA from 1989 to 2000. Immunohistochemical staining was evaluated by 2 anatomical pathologists who were blinded to outcome. The end point of this study was disease-free survival. Median followup was 5.9 years. A total of 96% of the tumor specimens stained positive for CXCR3. The mean percent of cells staining positive was 68% (range 0 to 100%). CXCR3 expression was not associated with other common clinicopathological features, such as Eastern Cooperative Oncology Group performance status, T stage, Fuhrman grade, vascular invasion or sarcomatoid features. Patients with low CXCR3 expression (less than 30%) had a significantly worse prognosis than patients with high CXCR3 expression with a 5-year disease-free survival rate of 57% vs 82% (p = 0.009). Multivariate Cox regression analysis retained T stage, Eastern Cooperative Oncology Group performance status, sarcomatoid features and CXCR3 as independent prognostic factors. CXCR3 is a novel molecular marker in patients with clear cell renal cell carcinoma. Its higher expression is an independent predictor of improved disease-free survival following nephrectomy for localized disease. Since CXCR3 is not associated with other clinicopathological prognostic factors, it may represent an ideal complementary molecular marker for identifying patients who are at higher risk for recurrence after nephrectomy.
    The Journal of urology 02/2008; 179(1):61-6. · 3.75 Impact Factor
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    ABSTRACT: Open partial nephrectomy is evolving as the standard of care for treatment of all amendable renal masses with laparoscopic and robotic assisted surgery being reported with increasing frequency. We reviewed the literature to assess the current state of knowledge regarding various outcomes with open, laparoscopic, and robotically assisted partial nephrectomy. Many studies report excellent long-term functional and oncological outcomes when evaluating open partial nephrectomy for both imperative and elective reasons. Preservation of renal function as compared with radical nephrectomy seems to be major benefit. With limited data and follow-up, laparoscopic partial nephrectomy is an evolving technique with oncological outcomes, in experienced hands, similar to those seen in large open partial nephrectomy series. However, laparoscopic partial nephrectomy seems to be associated with longer ischemia times, increased reoperative rates, and complication rates. Robotic nephrectomy is technically feasible but the overall virtues of such an approach remain to be determined. Concerns over preservation of renal function with any approach are paramount with continued efforts to limit warm ischemia without compromising oncological efficacy.
    The Cancer Journal 01/2008; 14(5):302-7. · 3.66 Impact Factor
  • Robert E Reiter, Stephen Riggs
    Nature Clinical Practice Urology 01/2008; 4(12):650-1. · 4.07 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays an important role in tumoral adaptation to hypoxic conditions by serving as a transcription factor for several crucial proteins, including vascular endothelial growth factor and carbonic anhydrase IX (CAIX). Here, we evaluated the significance of HIF-1 alpha in renal cell carcinoma (RCC). Immunohistochemical analysis was done on a tissue microarray constructed from paraffin-embedded primary tumor specimens from 357 patients treated by nephrectomy for RCC. Nuclear expression was evaluated by a single pathologist who was blinded to outcome. The expression levels were associated with pathologic variables and survival. HIF-1 alpha expression was greater in RCC than in benign tissue. Clear cell RCC showed the highest expression levels. In clear cell RCC, HIF-1 alpha was significantly correlated with markers of apoptosis (p21, p53), the mammalian target of rapamycin pathway (pAkt, p27), CXCR3, and proteins of the vascular endothelial growth factor family. HIF-1 alpha was correlated with CAIX and CAXII in localized, but not in metastatic RCC. HIF-1 alpha expression predicted outcome in metastatic patients: patients with high HIF-1 alpha expression (>35%) had significantly worse survival than patients with low expression (< or =35%); median survival, 13.5 versus 24.4 months, respectively (P = 0.005). Multivariate analysis retained HIF-1 alpha and CAIX expression as the strongest independent prognostic factors for patients with metastatic clear cell RCC. HIF-1 alpha is an important independent prognostic factor for patients with metastatic clear cell RCC. Because HIF-1 alpha and CAIX are independently and differentially regulated in metastatic clear cell RCC, both tumor markers can be complementary in predicting prognosis.
    Clinical Cancer Research 12/2007; 13(24):7388-93. · 7.84 Impact Factor
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    ABSTRACT: We identified prognostic factors for renal cell carcinoma with tumor thrombus extension and assessed whether the current T3 classification could be improved. We studied clinicopathological parameters in 321 consecutive patients who were surgically treated for renal cell carcinoma with tumor thrombus extension. Disease specific survival was evaluated with univariate and multivariate analysis. Harrell's C-index was used to assess the prognostic accuracy of prognostic models. Tumor thrombus extended into the renal vein in 166 patients, the inferior vena cava in 137 and the atrium in 18. Metastatic renal cell carcinoma was found in 198 patients (62%). The thrombus level had no impact on clinicopathological parameters or survival but perioperative morbidity and mortality increased with cranial extension of the thrombus. Mean followup was 49 months. Five and 10-year disease specific survival rates were 36% and 24%, respectively. On multivariate analysis Eastern Cooperative Oncology Group performance status, lymph node and distant metastases, sarcomatoid features and perinephric fat invasion were independent prognostic factors. Weight loss, anemia, collecting system invasion, incomplete surgical resection, nuclear grade and T classification were also significant prognosticators on univariate analysis. For patients with advanced disease the number of metastatic sites and the disease-free interval further predicted prognosis. The overall immunotherapy response rate was 19%, which decreased with cranial extension of the thrombus. Redefinition of the T3 classification with the incorporation of fat invasion improved prognostic accuracy, as shown by an increase in the C-index. Eastern Cooperative Oncology Group performance status, metastatic status, sarcomatoid features and concomitant perinephric fat invasion are the most powerful prognostic factors of survival in renal cell carcinoma with tumor thrombus extension. Our data indicate that a redefinition of the current T3 classification may improve its predictive accuracy. We propose that T3 renal cell carcinoma with fat invasion or thrombus extension alone should be classified as T3a, while that with thrombus extension plus fat invasion should be classified as T3b.
    The Journal of Urology 11/2007; 178(4 Pt 1):1189-95; discussion 1195. · 3.75 Impact Factor
  • Stephen B Riggs, Tobias Klatte, Arie S Belldegrun
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    ABSTRACT: The treatment of renal tumors with the technique of partial nephrectomy continues to evolve. The relevant literature reviewed confirmed the excellent oncological outcomes associated with partial nephrectomy in properly selected patients. In addition, much data is being accumulated regarding the safety and efficacy of this technique via a laparoscopic approach. With either approach, the chance for renal preservation would appear to be a major benefit while "non-hilar" clamping techniques during the open approach may maximize the likelihood for maintenance of long-term renal function.
    Urologic Oncology 01/2007; 25(6):520-2. · 3.65 Impact Factor
  • Stephen B Riggs, Tobias Klatte, Arie S Belldegrun
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    ABSTRACT: The treatment of renal tumors with the technique of partial nephrectomy continues to evolve. The relevant literature reviewed confirmed the excellent oncological outcomes associated with partial nephrectomy in properly selected patients. In addition, much data is being accumulated regarding the safety and efficacy of this technique via a laparoscopic approach. With either approach, the chance for renal preservation would appear to be a major benefit while "non-hilar" clamping techniques during the open approach may maximize the likelihood for maintenance of long-term renal function.
    Urologic Oncology 01/2007; 25(6):520-2. · 3.65 Impact Factor