RENAL CELL CARCINOMA: IMAGING AND THERAPY

May 28th, 2008 by admin

The increasing use of ultrasound and computerized tomography has led to over 50 per cent of renal cell carcinomas being incidentally detected. With an increasing number of small and asymptomatic tumors being identified it is particularly important for an accurate diagnosis to be reached via available imaging modalities to permit selection of patients for surgical treatment. The identification of patients suitable for management via nephron-sparing surgery is a key issue.

Advances in imaging have focused on the ability to distinguish malignant from nonmalignant tumors. Advanced assessments have aimed to identify the cancer subtype preoperatively in order to limit the requirement for surgery in carcinomas with low metastatic potential. Improved staging of renal tumors with magnetic resonance imaging and positron emission tomography has allowed more accurate preoperative assessment and planning of treatment for both organ-confined and extensive renal tumors. Radioimmunoscintigraphy and radioimmunotherapy also offer potential for therapeutic intervention at an antigen-directed level.

More accurate matching of therapeutic options to newly diagnosed renal carcinomas is now possible with contemporary imaging techniques in order to limit morbidity of surgical treatment. The potential for urologists to progress to treatment of renal malignancies via advanced radiographic techniques is fast approaching.

Reference

Bolton DM, Wong P, Lawrentschuk N. - University of Melbourne Departments of Surgery and

Urology, Austin Health, Melbourne, Australia

Curr Opin Urol. 2007 Sep;17(5):337-40

doi:10.1089/end.2006.0250

PubMed Abstract
PMID: 17762627

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INTRODUCTION

May 28th, 2008 by admin

Your kidneys are two bean-shaped organs, each about the size of your fist. They’re located behind your abdomen, one on each side of your spine. Like other major organs in the body, the kidneys can sometimes develop cancer. In adults, the most common type of kidney cancer is renal cell carcinoma (renal adenocarcinoma), which begins in the cells that line the small tubes within your kidneys. Children are more likely to develop a kind of kidney cancer called Wilms’ tumor.

Kidney cancer seldom causes problems in its early stages. But as a tumor grows, you may notice blood in your urine or experience unintentional weight loss or back pain that doesn’t go away. Kidney cancer cells may also spread (metastasize) outside your kidneys to nearby organs as well as to more distant sites in the body. Yet if kidney cancer is detected and  TREATED earilier.

Signs and symptoms

Kidney cancer rarely causes signs or symptoms in its early stages. In the later stages, the most common sign of both renal cell and transitional cell cancers is blood in the urine (hematuria). You may notice the blood when you urinate, or your doctor may detect it by urinalysis, a test that specifically checks the contents of your urine. Other possible signs and symptoms may include:

§                    A pain in the back just below the ribs that doesn’t go away

§                    A mass in the area of the kidneys that’s discovered during an examination

§                    Weight loss

§                    Fatigue

Intermittent fever

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DOES THIS CHILD HAVE A URINARY TRACT INFECTION

May 28th, 2008 by admin

Monday, 4 February 2008 - Urinary tract infection (UTI) is a frequently occurring pediatric illness that, if left untreated, can lead to permanent renal injury. Accordingly, accurate diagnosis of UTI is important. Shaikh et al. (2007) reviewed the diagnostic accuracy of symptoms and signs for the diagnosis of UTI in infants and children.

The authors searched MEDLINE and EMBASE databases for articles published between 1966 and October 2007, as well as a manual review of bibliographies of all articles meeting inclusion criteria, yielding 6988 potentially relevant articles. Studies were included if they contained data on signs or symptoms of UTI in children through age 18 years. Of 337 articles examined, 12 met all inclusion criteria. Two evaluators independently reviewed, rated, and abstracted data from each article.

In infants with fever, history of a previous UTI (likelihood ratio [LR] range, 2.3-2.9), temperature higher than 40 degrees C (LR range, 3.2-3.3), and suprapubic tenderness (LR, 4.4; 95% confidence interval [CI], 1.6-12.4) were the findings most useful for identifying those with a UTI. Among male infants, lack of circumcision increased the likelihood of a UTI (summary LR, 2.8; 95% CI, 1.9-4.3); and the presence of circumcision was the only finding with an LR of less than 0.5 (summary LR, 0.33; 95% CI, 0.18-0.63). Combinations of findings were more useful than individual findings in identifying infants with a UTI (for temperature >39 degrees C for >48 hours without another potential source for fever on examination, the LR for all findings present was 4.0; 95% CI, 1.2-13.0; and for temperature < 39 degrees C with another source for fever, the LR was 0.37; 95% CI, 0.16-0.85). In verbal children, abdominal pain (LR, 6.3; 95% CI, 2.5-16.0), back pain (LR, 3.6; 95% CI, 2.1-6.1), dysuria, frequency, or both (LR range, 2.2-2.8), and new-onset urinary incontinence (LR, 4.6; 95% CI, 2.8-7.6) increased the likelihood of a UTI.

Although individual signs and symptoms were helpful in the diagnosis of a UTI, they were not sufficiently accurate to definitively diagnose UTIs. Combination of findings can identify infants with a low likelihood of a UTI.

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LONG-TERM FATTY FISH CONSUMPTION AND RENAL CELL CARCINOMA INCIDENCE IN WOMEN

May 28th, 2008 by admin

Alicja Wolk, DMSc; Susanna C. Larsson, MSc; Jan-Erik Johansson, MD, PhD; Peter Ekman, MD, PhD

Context The epidemiological evidence that fatty fish consumption may be associated with the lower risk of several cancers is not consistent and no studies of renal cell carcinoma (RCC) exist.

Objective To examine the association between fatty and lean fish consumption and risk of RCC in women.

Design, Setting, and Participants The Swedish Mammography Cohort, a population-based prospective cohort study of 61 433 women aged 40 to 76 years without previous diagnosis of cancer at baseline (March 1, 1987-December 14, 1990). Participants filled in a food frequency questionnaire at baseline and in September 1997.

Main Outcome Measure Incident renal cell carcinoma.

Results During a mean of 15.3 years (940 357 person-years) of follow-up between 1987 and 2004, 150 incident RCC cases were diagnosed. After adjustment for potential confounders, an inverse association of fatty fish consumption with the risk of RCC was found (P for trend = .02), but no association was found with lean fish consumption. Compared with no consumption, the multivariate rate ratio (RR) was 0.56 (95% confidence interval [CI], 0.35-0.91) for women eating fatty fish once a week or more. Compared with women consistently reporting no fish consumption, the multivariate RR was 0.26 (95% CI, 0.10-0.67) for those women reporting consistent consumption of fatty fish at baseline and 1997 (based on a subset of 36 664 women who filled in the baseline and 1997 questionnaires, with 40 incident RCC cases during the 1998-2004 follow-up period).

Conclusion Our study suggests that consumption of fatty fish may reduce the occurrence of RCC in women.


Author Affiliations: Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Dr Wolk and Ms Larsson); Department of Urology and Center for Assessment of Medical Technology, University Hospital, Örebro (Dr Johansson); and Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm (Dr Ekman), Sweden.

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RENAL CELL CANCER

May 28th, 2008 by admin

Background Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease.

Methods In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group.

Results Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients who received interferon alone. Overall survival in the combination-therapy group did not differ significantly from that in the interferon group (hazard ratio, 0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the interferon group, the temsirolimus group, and the combination-therapy group were 7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia, and hyperlipidemia were more common in the temsirolimus group, whereas asthenia was more common in the interferon group. There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group (P=0.02).

Conclusions As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. (ClinicalTrials.gov number, NCT00065468 [ClinicalTrials.gov] .)


Source Information

From the Fox Chase Cancer Center, Philadelphia (G.H.); Sidney Kimmel Comprehensive Cancer Center, Baltimore (M.C.); Klinika Onkologii, Oddzial Chemioterapii, Poznan, Poland (P.T.); Our Lady of Mercy Medical Center, Bronx, NY (J.D.); University of California, Los Angeles, Los Angeles (R.F.); McMaster University, Hamilton, ON, Canada (A.K.); Lublin Oncological Center, Lublin, Poland (E.S.); Vanderbilt University Medical Center, Nashville (J.S.); Beth Israel Deaconess Medical Center, Boston (D.M.); National Institute of Oncology, Budapest, Hungary (I.B.); Military Medical Academy, Belgrade, Serbia (Z.K.); Regional Clinical Center of Urology and Nephrology, Kharkov, Ukraine (V.L.); University of Bonn, Bonn, Germany (I.G.H.S.-W.); Kemerovo State Medical Academy, Regional Clinical Hospital, Kemerovo, Russia (O.B.); Ege University Medical Faculty, Izmir, Turkey (E.G.); Wyeth Research, Cambridge, MA (T.O., S.L., L.M.); and Memorial Sloan-Kettering Cancer Center, New York (R.J.M.).

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HYPOTHYROIDISM IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH SUNITINIB

May 28th, 2008 by admin

Brian I. Rini, Ila Tamaskar, Phillip Shaheen, Renee Salas, Jorge Garcia, Laura Wood, Sethu Reddy, Robert Dreicer, Ronald M. Bukowski

Affiliations of authors: Department of Solid Tumor Oncology, Taussig Cancer Center (BIR, IT, PS, RS, JG, LW, RD, RMB), and Department of Endocrinology, Diabetes, and Metabolism (SR), Cleveland Clinic, Cleveland, OH

Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.

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BACKGROUND

May 28th, 2008 by admin

The course of advanced renal cell carcinoma is extremely variable, ranging from spontaneous remission to disease progression refractory to chemotherapy. Immunotherapy has held promise of improved outcomes based on uncontrolled studies and randomized controlled trials generally limited by small size and low power. OBJECTIVES: To evaluate immunotherapy for advanced renal cell carcinoma by comparing: (1) high dose interleukin-2 to other options and (2) interferon-alfa to other options. The primary outcome of interest was overall survival at one year, with remission as the main secondary outcome of interest. SEARCH STRATEGY: A systematic search of the CENTRAL, MEDLINE, and EMBASE databases was conducted for the period 1966 through end of December 2003. Handsearches were made of the proceedings of the periodic meetings of the American Urologic Association, the American Society of Clinical Oncology, ECCO - the European Cancer Conference, and the European Society of Medical Oncology for the period 1995 to June 2004. SELECTION CRITERIA: Randomized controlled trials that selected (or stratified) patients with advanced renal cell carcinoma, utilized an immunotherapeutic agent in at least one study arm, and reported remission or survival by allocation. Fifty-three identified studies involving 6117 patients were eligible and all but one reported remission; 32 of these studies reported the one-year survival outcome. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted each article by following a prospectively designed protocol. Dichotomous outcomes for treatment remission (partial plus complete) and for deaths at one year were used for the main comparisons. Survival hazard ratios were also used for studies of interferon-alfa versus controls, and for two randomized studies of the value of initial nephrectomy prior to interferon-alfa in fit patients with metastases detected at the time of diagnosis. MAIN RESULTS: Combined data for a variety of immunotherapies gave an overall chance of partial or complete remission of only 12.9% (99 study arms), compared to 2.5% in 10 non-immunotherapy control arms, and 4.3% in two placebo arms. Twenty-eight percent of these remissions were designated as complete (data from 45 studies). Median survival averaged 13.3 months (range by arm, 6 to 27+ months). The difference in remission rate between arms was poorly correlated with the difference in median survival so that remission rate is not a good surrogate or intermediate outcome for survival for advanced renal cancer. We were unable to identify any published randomized study of high-dose interleukin-2 versus a non-immunotherapy control, or of high-dose interleukin-2 versus interferon-alfa reporting survival. It has been established that reduced dose interleukin-2 given by intravenous bolus or by subcutaneous injection provides equivalent survival to high dose interleukin-2 with less toxicity. Results from four studies (644 patients) indicate that interferon-alfa is superior to controls (OR for death at one year = 0.56, 95% confidence interval 0.40 to 0.77). Using the method of Parmar 1998, the pooled overall hazard ratio for death was 0.74 (95% confidence interval 0.63 to 0.88). The weighted average median improvement in survival was 3.8 months. T he optimal dose and duration of interferon-alfa remains to be elucidated. The addition of a variety of enhancers, including lower dose intravenous or subcutaneous interleukin-2, has failed to improve survival compared to interferon-alfa alone. Two recent randomized studies have examined the role of initial nephrectomy prior to interferon-alfa therapy in highly selected fit patients with metastases at diagnosis and minimal symptoms: despite minimal improvement in the chance of remission, both studies of up-front nephrectomy improved median survival by 4.8 months over interferon-alfa alone. Recent studies have been examining anti-angiogenesis agents. A landmark study of bevacizumab, an anti-vascular endothelial growth factor antibody, was associated with significant prolongation of the time to progression of disease when given at high dose compared to low-dose or placebo therapy though frequency of remissions or survival were not improved. AUTHORS’ CONCLUSIONS: interferon-alfa provides a modest survival benefit compared to other commonly used treatments and should be considered for the control arm of future studies of systemic agents. In fit patients with metastases at diagnosis and minimal symptoms, nephrectomy followed by interferon-alfa gives the best survival strategy for fully validated therapies. The need for more effective specific therapy for this condition is apparent.

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KIDNEY (RENAL CELL) CANCER DIAGNOSIS

May 28th, 2008 by admin

How is kidney cancer (renal cell cancer) diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for kidney cancer may include the following:

  • Blood and urine laboratory tests.
  • Intravenous pyelogram (IVP) – a series of X-rays of the kidney, ureters and bladder with the injection of a contrast dye into the vein — to detect tumors, abnormalities, kidney stones or any obstructions, and to assess renal blood flow.
  • Renal angiography (also called arteriography) – a series of X-rays of the renal blood vessels with the injection of a contrast dye into a catheter, which is placed into the blood vessels of the kidney, to detect any signs of blockage or abnormalities affecting the blood supply to the kidneys.
  • Other imaging tests (to show the difference between diseased and healthy tissues), including the following:
    • Computed tomography scan (also called a CT or CAT scan) – a noninvasive procedure that takes cross-sectional images of the brain or other internal organs; to detect any abnormalities that may not show up on an ordinary X-ray.
    • Magnetic resonance imaging (MRI) – a noninvasive procedure that produces a two-dimensional view of an internal organ or structure, especially the brain and spinal cord.
    • Ultrasound (also called sonography) – a diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues and organs. Ultrasounds are used to view internal organs as they function and to assess blood flow through various vessels.

Based on results of other tests and procedures, a biopsy may be needed. A biopsy is a procedure in which a sample of the tumor is removed and sent to the laboratory for examination by a pathologist. Biopsy is the only sure way to diagnose cancer.

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CONTEXT

May 28th, 2008 by admin

Clinical surveys have revealed that incidental detection of renal cell carcinoma is rising because of increased use of imaging procedures. OBJECTIVE: To examine incidence, mortality, and survival trends of renal cell and renal pelvis cancers by age, sex, race, and tumor stage at diagnosis. DESIGN: Calculation of age-adjusted incidence and mortality rates, along with 5-year relative survival rates, using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. SETTING AND PARTICIPANTS: Patients diagnosed as having kidney cancer from 1975 through 1995 in the 9 geographic areas covered by tumor registries in the SEER program, which represent about 10% of the US population. MAIN OUTCOME MEASURES: Incidence, mortality, and 5-year relative survival rates by time periods. RESULTS: The age-adjusted incidence rates for renal cell carcinoma between 1975 and 1995 for white men, white women, black men, and black women were 9.6, 4.4, 11.1, and 4.9 per 100000 person-years, respectively. The corresponding rates for renal pelvis cancer were 1.5, 0.7, 0.8, and 0.5 per 100000 person-years. Renal cell cancer incidence rates increased steadily between 1975 and 1995, by 2.3% annually among white men, 3.1 % among white women, 3.9% among black men, and 4.3% among black women. Increases were greatest for localized tumors but were also seen for more advanced and unstaged tumors. In contrast, the incidence rates for renal pelvis cancer declined among white men and remained stable among white women and blacks. Although 5-year relative survival rates for patients with renal cell cancer improved among whites but not among blacks, kidney cancer mortality rates increased in all race and sex groups. CONCLUSIONS: Increasing detection of presymptomatic tumors by imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging, does not fully explain the upward incidence trends of renal cell carcinoma. Other factors may be contributing to the rapidly increasing incidence of renal cell cancer in the United States, particularly among blacks.

PMID: 10235157 [PubMed - indexed for MEDLINE]

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ALCOHOL INTAKE AND RENAL CELL CANCER IN A POOLED ANALYSIS OF 12 PROSPECTIVE STUDIES

May 28th, 2008 by admin

Jung Eun Lee, David J. Hunter, Donna Spiegelman, Hans-Olov Adami, Demetrius Albanes, Leslie Bernstein, Piet A. van den Brandt, Julie E. Buring, Eunyoung Cho, Aaron R. Folsom, Jo L. Freudenheim, Edward Giovannucci, Saxon Graham, Pamela L. Horn-Ross, Michael F. Leitzmann, Marjorie L. McCullough, Anthony B. Miller, Alexander S. Parker, Carmen Rodriguez, Thomas E. Rohan, Arthur Schatzkin, Leo J. Schouten, Mikko Virtanen, Walter C. Willett, Alicja Wolk, Shumin M. Zhang, Stephanie A. Smith-Warner

Affiliations of authors: Channing Laboratory (JEL, DJH, EC, EG, WCW) and Division of Preventive Medicine (JEB, SMZ), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition (DJH, EG, WCW, SASW), Epidemiology (DJH, DS, HOA, JEB, EG, WCW, SMZ, SASW), and Biostatistics (DS), Harvard School of Public Health, Boston, MA; Department of Medical Epidemiology and Biostatistics (HOA) and Division of Nutritional Epidemiology, National Institute of Environmental Medicine (AW), Karolinska Institutet, Stockholm, Sweden; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Health Services, Bethesda, MD (DA, MFL, AS); Department of Preventive Medicine and USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (LB); Department of Epidemiology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands (PAVDB, LJS); Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (ARF); Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, NY (JLF, SG); Northern California Cancer Center, Fremont, CA (PLHR); Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA (MLM, CR); Department of Public Health Sciences, University of Toronto, Toronto, ON, Canada (ABM); Department of Urology, Mayo Clinic College of Medicine, Jacksonville, FL (ASP); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland (MV)

Background: The association between alcohol intake and risk of renal cell cancer has been inconsistent in case–control studies. An inverse association between alcohol intake and risk of renal cell cancer has been suggested in a few prospective studies, but each of these studies included a small number of cases.

Methods: We performed a pooled analysis of 12 prospective studies that included 530469 women and 229575 men with maximum follow-up times of 7–20 years. All participants had completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RRs) for renal cell cancer were calculated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided.

Results: A total of 1430 (711 women and 719 men) cases of incident renal cell cancer were identified. The study-standardized incidence rates of renal cell cancer were 23 per 100000 person-years among nondrinkers and 15 per 100000 person-years among those who drank 15 g/day or more of alcohol. Compared with nondrinking, alcohol consumption (≥15 g/day, equivalent to slightly more than one alcoholic drink per day) was associated with a decreased risk of renal cell cancer (pooled multivariable RR = 0.72, 95% confidence interval = 0.60 to 0.86; Ptrend<.001); statistically significant inverse trends with increasing intake were seen in both women and men. No difference by sex was observed (Pheterogeneity = .89). Associations between alcohol intake and renal cell cancer were not statistically different across alcoholic beverage type (beer versus wine versus liquor) (P = .40).

Conclusion: Moderate alcohol consumption was associated with a lower risk of renal cell cancer among both women and men in this pooled analysis.

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