Early-stage Renal Cell Carcinoma Research Articles

Analysis of molecular profiling of renal cell carcinoma: Identification of a 4-microRNA signature as a prognostic value in patients with stage I-II disease.

395 Background: Renal-cell carcinoma (RCC) accounts for 3% of all cancers and produces over 12,000 deaths every year in the EE.UU. Currently, there is a need to identify stage I/II RCC patients with high risk of relapse following nephrectomy, given that these patients do not receive adjuvant treatment and ≈ 25% of them relapse. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNA and playing an important role as regulators of gene expression during tumorigenesis. Our willing is to define a miRNA expression profile associated with a high risk of relapse in early RCC. Methods: We analyzed 113 pts. with RCC stage I-II of a local data-base who had undergone nephrectomy from 2000 to 2008. RNA was extracted from FFPE samples using RecoverAll (Ambion). RNA samples were hybridized to Human miRNA Microarray Release 14.0, 8x15K (Agilent Technologies. Data were normalized using Quantile Normalization. Only 396 miRNAs with detectable signal in at least 10% of the hybridized samples were considered for further analysis. Identification of miRNAs related with recurrence risk and subsequent developing and validation of miRNA expression-based prediction models of recurrence risk were performed in BRB-ArrayTools v4.2.1. Results: We identified a 4-miRNA expression signature that distinguishes early stage RCC patients with low and high recurrence risk (p value = 0.0013; HR = 4.68 [1.82-12.0]). Distant recurrence free survival rate at five years was 97.4 and 81.2 for the low and high recurrence risk groups respectively. High levels of miR-424 were related with a high recurrence risk (p = 0.023). Conclusions: The TNM staging system lacks accuracy to identify prognostic markers of survival in early RCC. Our results suggest that specific miRNAs are involved in the recurrence of early disease. We have found a miRNA expression signature that identifies patients with high risk of developing distant metastasis using the FFPE sample of primary tumors. High expression levels of miR-424 were related with a high recurrence risk. MiR-424 is a hypoxia induced miRNA whose expression has been related with HIF-1α and HIF-2α stabilization and angiogenesis induction.

Advanced native kidney renal cell carcinoma in renal transplant recipients: role of sirolimus as dual anti-cancer and anti-rejection agent

The incidence of native kidney renal cell carcinoma (RCC) in renal transplant recipients is 15 times higher than the general population. These tumors are often found incidentally when imaging is performed for another indication. At that stage tumors are usually small and asymptomatic but it is possible that they may escape detection until a more advanced stage. Early stage RCC can be treated with radical nephrectomy but the treatment of advanced RCC may be more complicated and is associated with a poorer prognosis. RCC in context of renal transplant presents a special therapeutic challenge; balancing treatment of a potentially lethal malignancy in a redundant organ whilst maintaining good allograft function.We describe 2 cases of advanced renal cell carcinoma of native kidneys in renal transplant recipients and present our experience with sirolimus as a dual immunosuppressive and anti-tumor agent.

Significant variability in 10‐year cumulative radiation exposure incurred on different surveillance regimens after surgery for pT1 renal cancers: yet another reason to standardize protocols?

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The topic of radiation safety has been hotly debated not only in the mainstream media, but also in the urological literature. Radiation exposure has been examined in urological diseases such as testicular cancer and urinary stone disease, with resultant recommendations for modifying surveillance imaging. Radiation risk with respect to surveillance regimens after RCC surgery has yet to be examined. We consider this largely to be a result of RCC typically affecting older patients in whom cumulative radiation exposure may be less of a consideration. However, current population data emphasize that RCC diagnosis and therapy have an increasing impact upon younger patients with a longer life expectancy after treatment. Therefore, radiation considerations in this cohort of patients may be significant. To determine the 10-year cumulative radiation exposure incurred on different surveillance imaging protocols after surgery for pT1 renal cell carcinoma (RCC). The PubMed database was queried for surveillance protocols after surgery for RCC. There were two index lesions that were selected: (i) pT1a 3 cm, Fuhrman 2, clear cell and (ii) pT1b 5 cm, Fuhrman 3, clear cell. Exposure for single-phase chest computed tomography (CT), abdominal CT and chest X-ray were 7, 8 and 0.1 mSV, respectively. Calculations assumed biphasic CT scans, negative surgical margins and an Eastern Cooperative Oncology Group status of ≤1. In total, 12 published surveillance regimens were identified. For the first lesion (pT1a, clear cell, Fuhrman 2), we observed significant variability in the proposed regimens, ranging from no imaging to several CT scans of both chest and abdomen. Cumulative incurred radiation exposure for this index patient was in the range 0-102 mSv (mean, 34 mSv). When considering the second tumour (pT1b, clear cell, Fuhrman 3), all studies recommended some form of follow-up imaging, although regimens once again varied from annual chest X-ray to multiple CT scans of chest and abdomen. Cumulative incurred radiation exposure in this scenario was in the range 0.5-450 mSv (mean, 89 mSV). Surveillance protocols after surgery for early-stage RCC result in widely divergent levels of radiation exposure. Such considerations are increasingly paramount given concerns of radiation-induced secondary malignancies and present another reason to standardize follow-up protocols.

Extraspinal Findings at Lumbar Spine CT Examinations: Prevalence and Clinical Importance

To prospectively determine the prevalence and clinical importance of extraspinal abnormalities in adult outpatients undergoing computed tomography (CT) of the lumbar spine. Institutional review board approval was obtained for this prospective study. Informed consent was obtained from 400 consecutive adult outpatients (mean age, 49 years; 212 male and 188 female patients) undergoing lumbar spine CT for low back pain and/or radiculopathy. Those with known malignancy were excluded. Dedicated spinal and abdominal full-field-of-view (FOV) images for each patient were reviewed by at least one neuroradiologist and two body radiologists. Extraspinal abnormalities were classified according to the CT Colonography Reporting and Data System (C-RADS). The electronic medical record of the patients with C-RADS E3 and E4 extraspinal findings were reviewed to assess how many of these findings were previously unknown, and the patients were followed up 24-36 months after the initial CT to determine their work-up and outcome. Extraspinal findings were present on images in 162 (40.5%) of 400 lumbar spine CT examinations; 59 (14.8%) patients had indeterminate or clinically important findings requiring clinical correlation or further evaluation. After review of the electronic medical record, the prevalence of clinically important findings was 4.3%, comprising an early-stage renal cell carcinoma and transitional cell carcinoma, chronic lymphocytic leukemia, sarcoidosis, and 13 abdominal aortic aneurysms. Excluding anatomic variants, the full FOV was required to best visualize extraspinal abnormalities in 127 (79.4%) of 160 patients. Reviewing the full-FOV images from lumbar spine CT examinations will result in the detection of a small number of substantial extraspinal pathologic findings in addition to many benign incidental findings.

Incidence of benign versus malignant renal tumors in selected studies.

357 Background: Use of cross-sectional imaging has increased the detection rate for small renal tumors; more patients now present with early-stage renal cell carcinoma (RCC) or benign or indolent renal masses. Histopathology after surgical resection is the definitive method for characterizing renal tumors. Stage migration of renal masses creates uncertainty about the percentage of resected masses that will be benign vs malignant. We sought to better define these proportions through a targeted review of the literature. Methods: PubMed/select congresses were searched to identify the histologic classification of renal masses in a representative sample from the contemporary literature: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit: 2003–2011. Results: Most representative studies included procedures conducted in the mid-1990s to the mid-to-late 2000s. Studies origin was US (n=8), Korea (n=3), China, Japan, Germany, Austria, Australia, and multisite (Israel/France/US; all n=1). Only 8 studies had n≥500 (range, 70–10,404). The proportion of benign masses are shown (see Table); half of the studies reported values between 16% and 17%. The majority found that benign tumors were more likely to be smaller in size (<4 or <7 cm) than malignant tumors. 11 studies reported the RCC subtype (% clear cell range, 46%–83%). Conclusions: Benign renal tumors occur ~15% of the time and are more prevalent among small masses. Nearly 25% of resected lesions are benign or indolent and may not require surgery. Preoperative discrimination of more aggressive renal masses would be an important clinical advance that could improve clinicians’ diagnostic confidence and guide patient management. Funding: Wilex AG/IBA Molecular. [Table: see text]

Laparoscopic Nephrectomy: A Prospective, Nonrandomized Comparison With Open Surgical Nephrectomy.

Objective: To comparatively study the effectiveness of Laparoscopic nephrectomy vis-‡-vis Open nephrectomy in patients of benign non functioning kidney and early stage renal cell carcinoma. It was a prospective, non-randomized study. Patients and Methods: 160 patients underwent open (n=80) or laparoscopic nephrectomy (n=80).The comparison was made in relation to the operative time, intra-operative and postoperative complications, blood loss and transfusions, pain and analgesia requirements, hospital stay and convalescence. Results: The mean operative time (96 minutes Vs 74 minutes) was more in the laparoscopic group. The mean blood loss (127 ml Vs 104 ml) was more in the open group. The resumption of oral intake (30.3 hours Vs 33.6 hours) and removal of drain (2.35 days Vs 2.6 days) was earlier in the laparoscopic group. Intra-operative complications were more in laparoscopic group (5% Vs 2.5%). A total of 4 patients (5%) had to be converted to open because of failure to progress, and bleeding due to major vessel injury. Post operative complications were significantly more in open group. Mean hospital stay in open group was 6.3 ± 1.34 days, significantly more than laparoscopic group of 4.2 ± 1.22 days. Tumor recurrence was seen in both the groups. Conclusion: Laparoscopic nephrectomy for benign and early stage malignant disease is superior to open surgery in terms of reduced blood loss, postoperative complications, hospital stay and cosmetic outcome. The accumulated follow-up oncological data has shown equal oncological efficacy of laparoscopic radical nephrectomy and the results are comparable to open radical nephrectomy.

Low local metastatic rate may widen indication of nephron-sparing surgery for renal cell carcinoma

To explore the rationale for renal-sparing surgery as an alternative method to radical nephrectomy in the treatment of renal cell carcinoma (RCC), we analyzed clinical data from 94 patients diagnosed as having RCC. They were divided into 3 groups based on the maximum diameter of their tumor specimens. Group A had tumors size ranging from 0 to 4 cm, group B had tumors size ranging from 4 to 7 cm, and group C had tumors size greater than 7 cm. Tissue samples (5 cm) were taken from the upper pole side, lower pole side, and renal pelvic side of the tumor pseudocapsule; if the tumor was located on 1 pole of the kidney, samples were collected from 2 directions. The specimens were then embedded in paraffin and cut serially at segments 0 to 1, 1 to 3, and 3 to 5 cm. Staining with hematoxylin and eosin, anti-pancytokeratin, and vimentin was performed to determine tumor type and tumor infiltration. From the 94 patients analyzed, 2 patients in group A had RCC metastasis within 1 cm of tissue around the pseudocapsule, and 4 patients in groups B and C had lymph node metastasis without metastasis in the tissue 1 cm outside the pseudocapsule in all 3 directions described. There was no statistical significant difference found between the incidence of local metastasis of the various tumor sizes, suggesting that local metastasis of RCC is not associated with the size of the tumor. Based on the observation that incidences of local metastasis were low in early-stage RCC, we came to the conclusion that pseudocapsule of RCC tumor might have growth-limiting effect on the tumor enclosed. It is theoretically a safer and better surgical option for patients with RCC with a smaller size of tumor and indications for radical nephrectomy to undergo renal-sparing surgery with an excision margin of 1 cm of normal tissue around the pseudocapsule of the tumor.

Abstract No. 303: Advanced image fusion guidance and tracking for percutaneous renal cryoablation: Improved outcomes?

The use of advanced fusion imaging and electromagnetic (EM) tracking for guidance and navigation in percutaneous tumor ablation procedures has been described with uncertain benefits. Percutaneous renal cryoablation has encouraging early results as a minimally invasive, nephron sparing technique for select patients with early stage renal cell carcinoma (RCC). The objective of this study is to report the impact of CT/ US fusion imaging and EM tracking in percutaneous cryoablation of RCC.

Clinico-radio-pathologic features of a solitary solid renal mass at MDCT examination

incidental detection of solid renal masses has been increasing since the multidetector computed tomography (MDCT) scanner was introduced. to evaluate the clinico-radio-pathologic features of a solitary solid renal mass at MDCT examination. a total of 466 non-fatty solid renal masses in 466 patients undergoing nephrectomy were evaluated by MDCT examination. MDCT was performed before and after intravenous injection of contrast material. We obtained the incidences of benign tumors versus malignant tumors, renal cell carcinoma (RCC) versus non-RCC, and asymptomatic RCCs versus symptomatic RCCs. MDCT accuracy for detection of RCC was obtained with a threshold of more than 20 HU tumor attenuation difference between unenhanced and contrast-enhanced CT images. Nuclear grade was also compared between small RCCs (≤4 cm) and large RCCs (>4 cm). of 466 tumors, 443 (95%) were malignant and 23 (5%) were benign. Of 443 malignant tumors, 437 (99%) were RCC and 6 (1%) were non-RCC. Of 437 RCCs, 324 (74%) were asymptomatic and 113 (26%) were symptomatic. Asymptomatic RCCs (n=183, 56%) were more frequently pT1a than symptomatic RCCs (n=28, 25%) (P<0.05). MDCT accuracy for detection of RCC was 94% (437/466). Of 220 RCCs ≤4 cm, low grade RCC (53%) was more common than high grade RCC (47%). most solitary solid renal masses are early stage RCCs and can be diagnosed preoperatively at MDCT examination.

Retroperitoneal laparoscopic partial nephrectomy in the treatment of early stage renal cell carcinoma

Objective To evaluate the feasibility and the safety of retroperitoneal laparoscopic partial nephrectomy(LPN)for early stage renal cell carcinoma.Methods Retrospectively analyzed the medical records of 65 patients with single localized tumor.Fourty five cases were males and twenty cases were females.The mean age was 52 years.The clinical stage was T_1N_0M_0 in all patients.The renal artery was blocked with bulldog clamp and the tumor was resected with a margin of 5 to 10 mm of healthy renal parenchyma.Results Three patients required conversion to the open partial nephrectomy and one required conversion to the laparoscopic radical nephreetomy.The mean operative time was 120(70-210)min;the median warm-ischemia time was 32(21-55)min;the median overall estimated blood loss was 60(20-200)ml and the hospital stay was 10.5(7～15)d.During the follow-up of 3-56 months,All patients were alive without recurrence and had normal renal function.Conclusions Retroperitoneal laparoscopic partial nephrectomy is a treatment for early localized renal cell carcinoma. Key words: Kidney neoplasms; Carcinoma; Laparoscopy; Partial nephrectomy

489 USE OF PARTIAL NEPHRECTOMY IN RURAL VERSUS URBAN PRACTICE SETTINGS

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Cost Effectiveness II1 Apr 2010489 USE OF PARTIAL NEPHRECTOMY IN RURAL VERSUS URBAN PRACTICE SETTINGS Christopher Filson, Zaojun Ye, and David Miller Christopher FilsonChristopher Filson More articles by this author , Zaojun YeZaojun Ye More articles by this author , and David MillerDavid Miller More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.564AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial nephrectomy (PN) is underutilized for patients with early-stage renal cell carcinoma (RCC). For a variety of reasons, urologists working in rural settings may be particularly slow to adopt nephron-sparing surgery (NSS), potentially exacerbating unwarranted variations in the use of PN. In this context, we evaluated differences in the longitudinal utilization of PN among patients with RCC treated by surgeons working in rural versus urban practice settings. METHODS Using linked SEER-Medicare data, we identified patients who underwent surgical treatment for RCC from 1995 through 2005. We used a validated algorithm to determine whether each patient received NSS (i.e., partial nephrectomy) or radical nephrectomy. We used rural-urban commuting area codes (based on the zip code of the surgeon's primary office) to classify each surgeon's practice setting as rural (population < 10,000), micropolitan (population 10,000-50,000), or urban (population > 50,000). We then used bivariate and multivariate analyses to evaluate the relationship between surgeon practice setting and patient receipt of PN, adjusting for both tumor size and year of diagnosis. RESULTS We identified 12,899 patients treated surgically for RCC by 2,057 unique surgeons. Among the surgeons, 37 (1.8%) and 141 (6.8%) worked in rural and micropolitan practice settings, respectively. During the study interval, the proportion of patients treated with NSS by urban surgeons increased from 8.7% (1995) to 21.6% (2005), compared with an increase from 4.4% to 17.8% among patients treated by surgeons in non-urban settings (p<0.01) (Figure). After adjusting for tumor size and year of diagnosis, patients treated by rural (OR=0.32, 95% CI 0.12-0.87) and micropolitan (OR=0.62, 95% CI 0.43-0.89) surgeons remained significantly less likely than those treated by urban surgeons to receive NSS. CONCLUSIONS Patients with RCC who receive treatment from surgeons in non-urban settings are significantly less likely to undergo NSS. These data highlight the need for educational and other initiatives aimed at dismantling barriers to the adoption of NSS among urologists in more geographically-isolated practice settings. Ann Arbor, MI© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e193 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Filson More articles by this author Zaojun Ye More articles by this author David Miller More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Analysis of clinical characteristics of renal cell carcinoma in multi-centers

Objective To analyze the clinical characteristics of renal cell carcinoma (RCC) and unveil the current status of diagnosis and treatments. Methods The registry data from 23 medical centers cover different areas of China. A total of 2030 new cases of RCCs in the 23 centers from Au-gust 2007 to October 2008 were collected, in which 1975 cases had integrated data for analysis. The symptoms, diagnostic techniques, pathology features, and therapeutic selection were analyzed. Re-sults A total of 1975 new cases were reviewed, with 1329 males and 634 females. The male and fe-male ratio was about 2.1 : 1.0. Of all cases, 1238 patients (62.7%) were asymptomatic and detected by examination, while 711 patients (36.0%) were symptomatic. 1260 patients (63.8%) were clinical stage Ⅰ , most of them were asymptomatic. 1844 patients were treated surgically, 1500(81.3%) un-derwent radical nephrectomy, 325 (17. 6%) underwent partial nephrectomy. Among the operations, open operation was performed in 1493 cases(81.0%), laparoscopic procedure in 351 cases(19.0%). There were 1522(84.5%) clear cell carcinomas, 98 (5.44%) papilliform renal cell carcinomas. Con-clusions Routine health examination could be an important way to diagnose early stage RCC. Open radical nephrectomy is the most often used surgical technique among the centres of present study. Key words: Kidney neoplasms; Carcinoma; Physician's practice patterns

UP-2.080: Radical Nephrectomy for Early Stage Renal Cell Carcinoma Is a Significant Risk Factor for Chronic Kidney Disease

Early stage renal cell carcinoma (RCC) may be treated by radical or partial nephrectomy. Recent studies suggest that a decrease of overall kidney function follows radical nephrectomy and is a significant risk factor for chronic kidney disease (CKD). CKD is a known independent risk factor for cardiovascular disease. To compare incidence of the development of CKD transition of a long-term kidney function after surgical treatment to the early stage renal cell carcinoma.

Reporting Standards for Percutaneous Thermal Ablation of Renal Cell Carcinoma

WITH the increasing incidence of renal cell carcinoma (RCC) in the United States and the increasing proportion of patients with tumors detected at an early stage (1–5), nephron-sparing approaches are becoming more popular. These alternatives to radical nephrectomy include partial nephrectomy, wedge resection, and, more recently, in situ thermal ablation. Five-year survival rates after partial nephrectomy are equivalent to those after radical nephrectomy (6–8), supporting the rationale of in situ tumor destruction to further reduce morbidity and invasiveness. In situ thermal destruction of RCC uses techniques that destroy tumor tissue through heating (eg, radiofrequency [RF] ablation, microwave ablation, laser interstitial therapy, high-intensity focused ultrasound [US]) or freezing (eg, cryotherapy). Each of these techniques relies on controlled energy delivery to minimize collateral damage to normal renal parenchyma and other surrounding structures. In the United States, RF ablation and cryoablation are currently the most widely used techniques for in situ RCC destruction. Thermal ablation of RCC may be performed percutaneously, laparoscopically, or through open surgery. Our current understanding of the role of percutaneous thermal ablation in the management of primary RCC is limited by a paucity of prospective studies (9,10). Given the relative newness of this technology, most series to date report short-term or midterm outcomes, with no reports extending to 5 years of survival outcomes. No randomized trials have been performed to date comparing thermal ablation against a gold standard (ie, partial nephrectomy) or against other thermal ablation techniques. The optimal size range of RCC amenable to thermal ablation has not been clearly defined and is closely related to anatomic factors that influence the ability to deposit sufficient thermal dose to coagulate tissue, including proximity to major vessels and the urinary collecting system, which can act as a heat sink. The kidney has approximately four times the blood flow of the liver, so convective heat loss during thermal ablation is potentially significant (11). The role of percutaneous thermal ablation compared with laparoscopic or open thermal ablation also remains a topic of controversy. The combination of thermal ablation with other imageguided therapies (eg, transcatheter embolization) and adjuvant therapies such as chemotherapy and antiangiogenic agents for larger RCCs in patients who are poor operative candidates is another potential use of this technique. Although most recent reports of percutaneous RCC ablation have involved RF ablation, other ablation technologies are now available with percutaneous applicators (eg, cryoablation, microwave, laser interstitial therapy), and reporting standards should be uniform for all forms of energy-based ablation. This document provides recommended reporting standards for physicians performing percutaneous thermal ablation of primary RCC and will serve as a template in the design of clinical trials to further evaluate this technology. From the Section of Vascular and Interventional Radiology, Department of Radiology (T.W.I.C.), New York University School of Medicine, New York, New York; Department of Radiology (S.F.M.), University of Western Ontario, Peterborough Regional Health Center, Peterborough, Ontario, Canada; Department of Radiology, Gastrointestinal/Genitourinary Division (D.A.G.), Massachusetts General Hospital; Department of Radiology (S.N.G.), Beth Israel Deaconess Medical Center, Boston; Department of Radiology (C.J.G.), Lahey Clinic Medical Center, Burlington; Department of Radiology (D.A.P.), University of Massachusetts Memorial Health Care, Worcester, Massachusetts; Department of Radiology (T.B.K.), University of California San Diego Medical Center, San Diego, California; Department of Radiology (D.S.), The Reading Hospital and Medical Center, Reading, Pennsylvania; and Department of Radiology (J.F.C.), University of Colorado Health Sciences Center, Denver, Colorado. Received June 19, 2006; revision requested June 19; final revision received June 29; and accepted July 3. Address correspondence to T.W.I.C., c/o Tricia McClenny, Society of Interventional Radiology, 3975 Fair Ridge Dr, Suite 400 North, Fairfax, VA 22033; E-mail: mcclenny@sirweb.org

Imaging-Guided Percutaneous Ablation of Renal Cell Carcinoma: A Primer of How We Do It

This article is a primer in conducting an imaging-guided percutaneous renal ablation program based on the clinical experience of three institutions. Imaging-guided percutaneous ablation is becoming a viable alternative to surgery for the management of locally confined renal cell carcinoma. Conducting a successful renal tumor ablation program includes understanding the treatment options for early-stage renal cell carcinoma, selecting the appropriate patients, understanding the procedural techniques, and organizing a comprehensive follow-up.

Management of chemotherapy-induced remissions in patients with disseminated nonseminomatous germ cell tumors: A review of 98 consecutive patients

5037 Background: Management of patients (pts) with nonseminomatous testicular cancer obtaining a chemotherapy-induced complete serologic and radiographic remission (CR) with primary standard BEP chemotherapy is controversial. Approaches vary from the long standing recommendation for observation of such pts to automatic post-chemotherapy retroperitoneal lymph node dissection (RPLND) for all pts (even those in radiographic CR) (Stephenson JCO 25:5597, 2007). Methods: We reviewed 98 consecutive pts (stage IS-III) initially managed with chemotherapy by a single medical oncologist (CN) from 6–98 to 12–07. Pts obtaining CR were observed without surgery. Results: Results are outlined in the table below. 95/98 pts (97%) are alive and currently disease-free with follow-ranging from 2 months to 108 months (median 34 months). There have been three deaths (one germ cell tumor, one second cancer, one gunshot wound). There have been 4 second cancers (2nd primary testis cancer, hairy cell leukemia, early stage renal cell carcinoma, and luminal small bowel adenocarcinoma). There have been no late recurrences of germ cell tumor in this population. With particular emphasis on the behavior of those pts obtaining CR with primary chemotherapy, 4/56 CR pts (7%) experienced a second event. Two pts (both stage III) had either pulmonary or multi-site recurrence of germ cell cancer and two pts (both stage II) had abdominal recurrence of teratoma (14, 34 months). Recurrence appeared in 3/27 (11%) of pts who were NED-teratoma and 2/11 (18%) of pts who were NED-necrosis after primary chemotherapy and surgery. Had uniform application of post-chemotherapy surgery been applied to pts obtaining CR, 56 RPLNDs would have been performed with no patient gaining permanent benefit. Conclusions: Pts obtaining CR after primary standard BEP chemotherapy can be safely observed without routine application of post chemotherapy surgery. Late relapse of cancer and recurrent teratoma are very rare events. Outcome by stage and remission status Stage CR PR mk- NED-Ter NED-Ca NED-nec Relapse by stage IS (n=10) 10 (100%) 0 0 0 0 1/10 (10%) 1 Ter II (n=41) 26 (63%) 1 (2%) 12 (29%) 0 2 (5%) 3/41 (7%) 3 Ter III (n=47) 20 (42%) 3 (6%) 15 (32%) 0 9 (19%) 6/47 (13%) 6 Ca Relapse by remission status 4/56 (7%) 2 Ter/2 Ca 1/4 (25%) 1 Ter 3/27 (11%) 1 Ter/2 Ca 0 2/11 (18%) 2 Ca No significant financial relationships to disclose.

Current management of renal cell carcinoma and targeted therapy.

The aim of this review is to provide an update on the current management of renal cell carcinoma (RCC) and targeted molecular therapy for metastatic RCC. A Pubmed database search was performed using the keywords "renal cell carcinoma, treatment, management, localized disease, metastatic disease and targeted therapy" covering 1995 to 2006. The most recent articles published having clinical relevance were reviewed for the preparation of this paper. Surgery is considered as the only curative treatment for localized RCC. Currently, open radical nephrectomy is mainly performed in patients with large tumor size, locally advanced tumors and tumor thrombus extending into the vena cava. Nephron sparing surgery (NSS) is the most commonly performed procedure with excellent local cancer control in small, resectable renal tumors. Increasingly, laparoscopy is being performed and now recommended for early-stage RCCs unsuitable for NSS. Laparoscopic radical nephrectomy seems to be providing long-term cancer control comparable to open radical nephrectomy. Laparoscopic NSS is now available particularly in patients with a relatively small and peripheral renal tumor. The current therapy for metastatic RCC is inadequate and surgery is an important component of the treatment with combined immunotherapy in which response rates remain at about 15% to 25%. In the past several years, significant advances in the underlying biological mechanisms of RCC development have permitted the design of new molecularly targeted therapeutics such as antibodies, tumor vaccines, anti-angiogenesis agents and small molecule tyrosine kinase inhibitors in order to improve treatment options. Surgery is the only curative treatment for localized RCC and NSS cures most of the patients with early-stage disease. Currently laparoscopy is recommended for early-stage RCCs unsuitable for NSS. Better understanding of the molecular pathways of carcinogenesis in RCC leads to the discovery of new drugs which can prolong survival in metastatic RCC.

Thrombocytosis is associated with a significant increase in the cancer specific death rate after radical nephrectomy.

We have previously reported that patients with advanced renal cell carcinoma and a normal platelet count of 400,000/mm. have a 64% increase in life expectancy compared with those with thrombocytosis. We determined whether thrombocytosis was predictive of death from renal cell carcinoma after radical nephrectomy was performed with curative intent for early stage disease. We reviewed the records of 204 patients with renal cell carcinoma who underwent radical nephrectomy with curative intent between June 1993 and January 2000 at Emory University Hospital. Survival, pathological grade and stage were recorded from the Emory Winship Cancer Institute tumor registry. Platelet counts were recorded and any patient with at least 1 platelet count of greater than 400,000/mm. was classified with thrombocytosis. Those with a platelet count of 400,000/mm. were classified with a normal platelet count. There were 26 patients with thrombocytosis and 178 patients with persistently normal platelet counts. The overall and cancer specific death rate in the 26 patients with thrombocytosis was 50% and 42%, respectively. The overall mean time between nephrectomy and death was 12.1 months in this group. The overall and cancer specific death rate in the 178 patients with a normal platelet count was 15.2% and 7.3%, respectively. Mean time to death was 22.6 months in this group. Differences in the overall and cancer specific death rates were highly statistically significant as well as clinically significant. These differences remained significant after controlling for grade, stage and histological type of cancer. This study documents the association of thrombocytosis with decreased survival in patients with renal cell carcinoma. In those who undergo nephrectomy for early stage renal cell carcinoma with a perioperative platelet count of greater than 400,000/mm. the cancer specific death rate from renal cell carcinoma is greater than 5 times the rate in patients with a persistently normal platelet counts after radical nephrectomy. The platelet count appears to be a new and powerful independent prognosticator in patients with renal cell carcinoma who undergo radical nephrectomy for presumed localized disease.

Lessons learned in the surgical management of renal cell carcinoma

Surgical excision, the mainstay of management of renal cell carcinoma (RCC), has evolved significantly over the last 4 decades. Radiological imaging is crucial to the diagnosis and staging of RCC, and technological advances have facilitated more precise preoperative assessment. Additionally, wider use of cross-sectional imaging modalities has led to increasing incidental diagnosis of small, early-stage RCC. Nephron-sparing surgery (NSS), originally developed to treat RCC arising in a solitary functioning kidney, has been demonstrated to be a safe and effective alternative to radical nephrectomy. NSS is now also applicable to tumors of suitable size and anatomy in patients with a normal contralateral kidney, thus facilitating preservation of renal function and management of metachronous contralateral pathology. Laparoscopic and percutaneous approaches have developed over the last decade, thus providing minimally invasive modalities, with shortened convalescence and improved cosmesis. Advanced RCC, involving venous extension or nodal spread, is increasingly amenable to surgical management, although appropriate patient selection is crucial. Furthermore, surgical excision of the primary lesion appears to be an integral part of systemic therapy for metastatic RCC.

Renal Cell Carcinoma Following Bariatric Surgery

Obesity, hypertension, smoking, and amphetamine diet pills increase the risk for renal cell carcinoma (RCC). Obesity causes a four-fold increase. We report our 11-year experience with RCC after bariatric operations. 5 patients with RCC were identified out of 2,287 bariatric surgical patients since 1993 on retrospective chart review. 4 of the 5 patients were females. At time of their bariatric operation, patients were age 29-52 (43.4) years, weighed 109-158 (129.8) kg, and BMI was 43-60 (49.4). All tumors were incidentally discovered 8-66 (27.4) months postoperatively when the patients weighed 54-94 (71.4) kg, with BMI 21-34 (26.6). Preoperative renal ultrasound obtained within 3 months of the bariatric operation was normal in 4; the other did not have a preoperative study. The latter patient had a vertical banded gastroplasty 12 years before and the RCC was discovered 5 1/2 years later during work-up for a revision. 3 had a distal gastric bypass and 1 underwent adjustable gastric banding. 4 of the patients had a radical nephrectomy and 1 underwent a partial nephrectomy. Tumors were 2.0-8.7 (4.4) cm in size, and all were clear-cell RCC without vascular or extrarenal involvement. None has had recurrence at 3-67 (30.8) months follow-up. 1 patient died from a stroke 18 months later. Reversal of obesity following bariatric surgery does not eliminate risk for RCC. Preoperative and annual postoperative ultrasonography may be useful in identifying early stage RCC. Lesions that are not pure cysts must be evaluated with CT scans or MRI. Nephrectomy may be curative.