National Cancer Institute®
Last Modified: July 1, 2002
UI - 12010834
AU - Bregni M; Dodero A; Peccatori J; Pescarollo A; Bernardi M; Sassi I;
TI - Voena C; Zaniboni A; Bordignon C; Corradini P Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer.
SO - Blood 2002 Jun 1;99(11):4234-6
AD - Bone Marrow Transplant Unit and Gene Therapy Program and the Division of Pathology, Istituto H San Raffaele, Milano, Italy. firstname.lastname@example.org
The feasibility and toxicity of allogeneic stem cell transplantation after nonmyeloablative conditioning including thiotepa, fludarabine, and cyclophosphamide have been investigated in 6 patients with breast cancer and 7 patients with renal cell cancer. The program included the use of escalating doses of donor lymphocyte infusions (DLI) and/or interferon alpha (IFNalpha) for patients showing no tumor response and no graft-versus-host disease (GVHD). Patients were at high risk of transplant-related mortality (TRM) because of age, advanced stage, and previous treatments. We observed a partial remission in 4 renal cancer and in 2 breast cancer patients (one at the molecular level in the bone marrow), occurring after cyclosporine withdrawal or after DLI and/or IFNalpha. All the responses were accompanied by the occurrence of acute GVHD. We conclude that reduced-intensity allogeneic stem cell transplantation is a feasible procedure in renal and breast cancer, and that the exploitation of graft-versus-tumor effect after DLI is a promising finding.
UI - 11598443
AU - Bassi P; Iafrate M; Longo F; Iannello A; Mostaccio G; Ingrassia A;
TI - Repele M; Tavolini IM Intracavitary therapy of noninvasive transitional cell carcinomas of the upper urinary tract. A review of the literature.
SO - Urol Int 2001;67(3):189-94
AD - Department of Urology, University of Padua Medical School, Via Giustiniani, 2, I-35128 Padua, Italy. email@example.com
Noninvasive (stages Ta, T1, Tis) transitional cell carcinomas of the upper urinary tract are suitable for a conservative therapeutic approach. Intracavitary therapy (alone or as adjuvant treatment) has recently been proposed and successfully used by some authors. Even though bacillus Calmette-Guerin is the most frequent agent employed, chemotherapeutic drugs, such as mitomycin C and thiotepa, have also been successfully used. The current information available in the literature is therefore reviewed. According to the data available, intracavitary therapy is a worthwhile conservative therapeutic option for noninvasive upper urinary tract urotheliomas with acceptable side effects. For this reason it may be included in the routine urological armamentarium.
UI - 11598445
AU - Hara I; Miyake H; Hara S; Arakawa S; Hanioka K; Kamidono S
TI - Role of percutaneous image-guided biopsy in the evaluation of renal masses.
SO - Urol Int 2001;67(3):199-202
AD - Department of Urology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
OBJECTIVE: The objective of the present study was to evaluate the indications, accuracy, complications and impact of image-guided percutaneous biopsy of renal masses. MATERIALS AND METHODS: Between 1994 and 1999, percutaneous biopsies under ultrasonography or computerized tomography guidance were performed in 33 patients with renal mass (22 men and 11 women, mean age 57.5 years, range 21-88). We retrospectively analyzed the relationship between clinical and histopathological findings, and discuss the appropriateness of the indications for image-guided percutaneous biopsy in the diagnosis of renal masses. RESULTS: The indications used in our institution were as follows: (1) clinical and radiological findings to suggest a diagnosis other than primary renal cell carcinoma (RCC) (n = 15); (2) suspicious lesions of RCC in multiple cystic renal masses (n = 7); (3) differentiation of transitional cell carcinoma of the renal pelvis from RCC (n = 7); (4) differentiation of angiomyolipoma from RCC (n = 4). Sufficient amounts of tissues were obtained from all patients for pathological diagnosis. Among 33 patients, 21 (63.6%) were diagnosed positive for malignancy, and 15 underwent surgical intervention. The histopathological findings between percutaneous biopsy and surgically resected tissue were identical in 13 cases (86.7%). No patient developed major complications requiring surgical treatment. CONCLUSION: If performed under appropriate selection of patients, percutaneous image-guided biopsy is a safe, reliable and accurate method of managing suspicious and/or indeterminate renal mass, and may contribute to the selection of appropriate clinical management by avoiding unnecessary procedures. Copyright 2001 S. Karger AG, Basel
UI - 11598446
AU - Gacci M; Rizzo M; Lapini A; Serni S; Stefanucci S; Carini M
TI - Imperative indications for conservative surgery for renal cell carcinoma: 20 years' experience.
SO - Urol Int 2001;67(3):203-8
AD - Department of Urology, University of Florence, Viale Pieraccini 18, I-50139 Florence, Italy.
INTRODUCTION: Radical nephrectomy is the treatment of first choice for unilateral renal cell carcinoma (RCC) with a healthy contralateral kidney; however, the current standard for dealing with RCC in patients with a solitary kidney, bilateral tumor and renal or systemic disease inducing a progressive impairment of renal function is nephron-sparing patients (39 men and 23 women, 33-77 years old, mean age 60.6 years) with RCC underwent nephron-sparing surgery. The patients were divided in to two groups according to treatment indication: 46 patients with bilateral tumor (n = 21) or solitary kidney (n = 25) and 16 patients with renal or systemic disease that could damage the contralateral kidney. Survival curves were calculated according to the Kaplan-Meyer method. RESULTS: In the first group 3 patients died postoperatively, and 3 were lost to follow-up; 12 patients (27.9%) had malignant recurrence and 5 (11.6%) died of local recurrence or systemic diffusion. The probability of local or systemic tumor recurrence was 9.9% at 2 years, 20.2% at 5 years and 24.7% at 10 years; the probability of survival was 100% at 2 years, 91.9% at 5 years and 81.9% at 10 years. In the second group 3 patients died of unrelated causes and 1 was lost to follow-up; 4 patients (25%) had a malignant recurrence and 2 (12.5%) died of systemic diffusion of RCC. The probability of tumor recurrence was 13.0% at 2 years, 19.7% at 5 years and 26.4% at 10 years, the probability of survival was 100% at 2 years, 93.3% at 5 years and 86.1% at 10 years. CONCLUSIONS: In our experience nephron-sparing surgery seems justified in patients with a solitary kidney, bilateral tumor or a disease that potentially damages renal function. Tumor diameter and stage, incidental or symptomatic tumor presentation and specific indication for conservative surgery determine the prognosis. Copyright 2001 S. Karger AG, Basel
UI - 12034628
AU - Kim JK; Kim TK; Ahn HJ; Kim CS; Kim KR; Cho KS
TI - Differentiation of subtypes of renal cell carcinoma on helical CT scans.
SO - AJR Am J Roentgenol 2002 Jun;178(6):1499-506
AD - Department of Radiology, Asan Medical Center, University of Ulsan, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, South Korea.
OBJECTIVE: The purpose of our study was to differentiate subtypes of renal cell carcinoma on helical CT scans. MATERIALS AND METHODS: We reviewed CT scans of four subtypes of renal cell carcinoma: 76 conventional (clear cell), 19 papillary, 13 chromophobe, and two collecting duct. Biphasic CT scans (unenhanced, corticomedullary, and excretory phase scans) were obtained in 61 patients, and monophasic CT scans (unenhanced and excretory phase scans) in 49. We compared patient age and sex; tumor size; degree and pattern (homogeneous, heterogeneous, predominantly peripheral) of enhancement; presence or absence of calcification; and tumor-spreading patterns including perinephric change, venous invasion, and lymphadenopathy in four subtypes. RESULTS: Conventional renal carcinoma showed stronger enhancement than the other subtypes (p < 0.05): 106 +/- 48 H (mean +/- SD) in the corticomedullary phase and 62 +/- 25 H in the excretory phase. The sensitivity and specificity for differentiating conventional renal carcinoma from the other subtypes were 74% and 100% when 84 H was used as the cutoff value in the corticomedullary phase and 84% and 91% when 44 H was used as the cutoff value in the excretory phase. Conventional (84%), papillary (74%), and collecting duct (100%) renal carcinomas tended to show heterogeneous or predominantly peripheral enhancement, whereas chromophobe renal carcinoma (69%) usually showed homogeneous enhancement. Calcification was more common in papillary (32%) and chromophobe (38%) renal carcinomas than in conventional renal carcinoma (11%) (p < 0.05). Perinephric change and venous invasion were not noted in chromophobe renal carcinoma, whereas both were common in collecting duct renal carcinoma. CONCLUSION: For the differentiation of the subtypes of renal cell carcinoma, degree of enhancement is the most valuable parameter; enhancement pattern, the presence or absence of calcification, and tumor-spreading patterns can serve supplemental roles in the identification of the subtype of renal cell carcinoma.
UI - 11866983
AU - He L; Fu L; Wang L; Li P; Lang Z
TI - [A clinicopathological study of clear cell sarcoma of the kidney]
SO - Zhonghua Bing Li Xue Za Zhi 2001 Dec;30(6):422-5
AD - Department of Pathology, Beijing Children's Hospital, Beijing 100045, China.
OBJECTIVE: To study the clinicopathological, immunohistochemical features and the histogenesis of clear cell sarcoma of the kidney (CCSK). METHODS: CCSK specimens from 45 pediatric cases, including 31 male and 14 female with an age range from 3 months to 12 years (mean of 3.2 years), were retrieved. Routine pathological, immunohistochemical and electron microscopic methods were utilized to analyze the CCSK specimens. RESULTS: 35 of the 45 cases were followed from 6 to 192 months. 15 patients presented with bone metastases, 6 had lung or liver metastases, 8 recurred and 20 died. Age and clinical stage at diagnosis correlated with the rate of survival. Histologically, the classic pattern of CCSK consisted of cells with pale cytoplasm, fine nuclear chromatin and indistinct nucleoli separated by an arborizing fibrovascular stroma. Other patterns were identified, including myxoid, spindle, palisading, epithelioid, sclerosing, cellular, cystic, and angiectatic. All tumors contained multiple patterns. Immunohistochemically, all cases were positive for vimentin, but negative for EMA, CK, desmin, actin, S-100, NSE, CD99, CD34 and LCA. Electron microscopy of 9 cases showed features of primitive cell conjunction and few organelles. CONCLUSION: CCSK is a common renal neoplasm of childhood. CCSK may arise from renal mesenchymal cells and has the propensity to metastasize to the bone with poor clinical outcome.
UI - 12028626
AU - Sung GT; Gill IS
TI - Anatomic landmarks and time management during retroperitoneoscopic radical nephrectomy.
SO - J Endourol 2002 Apr;16(3):165-9
AD - Section of Laparoscopic and Minimally Invasive Surgery, Urological Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
BACKGROUND AND PURPOSE: Retroperitoneoscopy has not been widely considered the preferred approach to laparoscopic radical nephrectomy for cancer, in part because the retroperitoneal anatomic landmarks have not been well defined. The aim of this study is to provide prospective, objective data on retroperitoneoscopic radical nephrectomy with regard to anatomic landmarks and time management of the sequential operative steps. MATERIALS AND METHODS: A uniform database was devised to record predetermined intraoperative parameters prospectively in 18 consecutive retroperitoneoscopic radical nephrectomies. RESULTS: A three- or four-port technique was employed to perform 10 left and 8 right retroperitoneoscopic radical nephrectomies. Initial balloon dilation was routinely performed outside of and posterior to Gerota's fascia. The anatomic landmarks visible immediately on initial insertion of the laparoscope were: psoas muscle in 18 cases (100%), Gerota's fascia in 18 (100%), peritoneal reflection in 15 (83%), ureter and/or gonadal vein in 11 (61%), and renal artery pulsations in 10 (56%). Aortic pulsations were seen in 9 of 10 left (90%) and the inferior vena cava in 2 of 8 right (25%) radical nephrectomies. The mean surgical time was 203 +/- 52.9 minutes (range 105-290 minutes). The sequential operative steps and their individual time breakdowns were: port placement 12 +/- 3.9 minutes, hilar dissection 63 +/- 29.1 minutes, adrenal mobilization 49 +/- 12.1 minutes, specimen mobilization 19 +/- 20.8 minutes, and specimen entrapment and exit 23 +/- 18.2 minutes. When the initial balloon dilation resulted in visibility of four or more anatomic landmarks, the hilar dissection time was significantly shorter (P < 0.001). CONCLUSIONS: Proper development of the retroperitoneal space and identification of adequate anatomic landmarks is important during retroperitoneoscopy. This timed analysis of the sequential operative steps of retroperitoneoscopic radical nephrectomy has served as an important self-assessment tool for us in improving our surgical technique. As a result, our surgical time for retroperitoneoscopic radical nephrectomy has decreased from the earlier 4- to 5-hour range to the current 2- to 3-hour range.
UI - 10886077
AU - Dhote R; Pellicer-Coeuret M; Thiounn N; Debre B; Vidal-Trecan G
TI - Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention.
SO - BJU Int 2000 Jul;86(1):20-7
AD - Service de Sante Publique, Service de Medecine Interne, Universite Rene Descartes, CHU Cochin Port-Royal, Saint-Jacques, Paris, France. firstname.lastname@example.org
UI - 12076276
AU - Oh RR; Park JY; Lee JH; Shin MS; Kim HS; Lee SK; Kim YS; Lee SH; Lee SN;
TI - Yang YM; Yoo NJ; Lee JY; Park WS Expression of HGF/SF and Met protein is associated with genetic alterations of VHL gene in primary renal cell carcinomas.
SO - APMIS 2002 Mar;110(3):229-38
AD - Department of Pathology and Genetic Oncology Laboratory, College of Medicine, The Catholic University of Korea, Seoul.
We analyzed the genetic alterations of VHL, HGF/SF, and Met genes and the expression pattern of HGF/SF and Met protein in 26 renal cell carcinomas (RCCs). We found five mutations of the VHL gene and frequent LOH (50%) only in non-papillary clear cell RCC. We found six cases in which the CpG island of VHL was methylated. In addition, one missense mutation of the HGF/SF gene was detected in clear cell RCC. HGF/SF and Met protein were expressed in 84.6% and 80.7% of RCCs, respectively. All of the cases with the genetic alterations of VHL or HGF/SF demonstrated strong expression of HGF/SF and Met protein in RCC cells. Statistically, genetic alterations of VHL and HGF/SF were significantly correlated with HGF/SF and Met expression (Fisher's exact test, p=0.022 and p=0.0070). Thus, these results strongly suggest that the expression of HGF/SF and Met protein is closely associated with the genetic alterations of VHL and HGF/SF in primary RCCs.
UI - 12050483
AU - Harada H; Furuya M; Ishikura H; Shindo J; Koyanagi T; Yoshiki T
TI - Expression of matrix metalloproteinase in the fluids of renal cystic lesions.
SO - J Urol 2002 Jul;168(1):19-22
AD - Division of Pathophysiological Science, Department of Pathology/Pathophysiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
PURPOSE: Cystic lesions of the kidney are common conditions usually diagnosed by imaging. Although simple cysts are easy to diagnose, preoperative diagnosis of a complicated cystic lesion can be difficult. There is little information available on the biological activity of cystic fluid and associations with clinicopathological findings. We analyzed the expression of matrix metalloproteinase (MMP) in the fluids of benign and malignant renal cystic lesions to clarify matriolytic activities in the cyst. MATERIALS AND METHODS: Included in this study were 22 samples of cystic fluids from renal cystic lesions, including 14 benign cysts and 8 cystic renal cell carcinomas. MMP-2 and 9 was determined in fluids using gelatin zymography and enzyme-linked immunosorbent assay. RESULTS: MMP-2 expression was ubiquitously observed on zymography except for 2 benign cysts associated with acquired cystic disease of the kidney. MMP-9 was detected in 7 of 8 carcinomas but in only 2 of 14 benign cysts (p <0.01). The concentration of MMP-2 and 9 was significantly higher in cystic carcinomas than in benign cysts (p <0.01). CONCLUSIONS: Our data show that MMPs were detectable in cystic fluids in the presence of renal cystic changes. MMP-2 and 9 are more abundant in cystic carcinoma fluids than in benign cystic fluids. These observations suggest that matriolytic enzymes in renal cystic fluid reflect biological aggressiveness and in part explain the pathogenesis of renal cystic lesions.
UI - 12050480
AU - Yohannes P; Smith AD
TI - The endourological management of complications associated with horseshoe kidney.
SO - J Urol 2002 Jul;168(1):5-8
AD - Department of Urology, Albert Einstein College of Medicine, Long Island Jewish Medical Center Campus, New Hyde Park, New York, USA.
PURPOSE: Horseshoe kidneys are the most common renal fusion anomalies. Ureteropelvic junction obstruction, urolithiasis and renal malignancies are the most common complications that occur in this patient population. Endourological management of these complications has decreased perioperative morbidity. We identified the applications of minimally invasive surgery for treating complications secondary to horseshoe kidney. MATERIALS AND METHODS: A comprehensive literature review of the different endourological approaches in the management of complications secondary to horseshoe kidney was performed using MEDLINE. RESULTS: Ureteropelvic junction obstruction can be managed by percutaneous endopyelotomy or laparoscopic pyeloplasty with good results. Small stones associated with horseshoe kidney are best managed by shock wave lithotripsy, while stones that have failed management by shock wave lithotripsy or are greater than 2 cm. are best managed percutaneously. All patients should undergo metabolic evaluation. Ureteroscopy or shock wave lithotripsy is associated with a higher residual stone rate than the percutaneous approach. Laparoscopic nephrectomy is a safe and feasible option for benign and malignant horseshoe kidney diseases. CONCLUSIONS: Endourological techniques can be safe and effective for treating complications secondary to horseshoe kidney.
UI - 12050491
AU - Sweeney P; El-Naggar AK; Lin SH; Pisters LL
TI - Biological significance of c-met over expression in papillary renal cell carcinoma.
SO - J Urol 2002 Jul;168(1):51-5
AD - Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
PURPOSE: Hereditary papillary renal cell carcinoma is associated with mutations of the c-met proto-oncogene. Similar aberrations have been described at a molecular level in up to 13% of sporadic papillary renal cell carcinomas. We assessed c-met expression in papillary renal cell carcinomas and evaluated the prognostic significance of c-met expression in patients with this tumor. MATERIALS AND METHODS: We performed immunohistochemical testing to identify c-met expression in archival specimens of 55 papillary renal cell carcinomas in 51 patients. Only 1 patient reported a family history of renal malignancy. RESULTS: We identified c-met protein expression in the cytoplasm and cell membrane of 80% and 56% of these tumors, respectively. c-met expression significantly correlated with higher stage tumors (p = 0.004) but it was not associated with Fuhrman nuclear grade (p = 0.157). A trend toward a higher overall survival rate was noted in patients in whom tumors did not express c-met but this association failed to achieve statistical significance (p = 0.07). CONCLUSIONS: Our study indicates that c-met over expression may be associated with an aggressive phenotype in these tumors.
UI - 12050492
AU - Ward JF; Blute ML; Cheville JC; Lohse CM; Weaver AL; Zincke H
TI - The influence of pNx/pN0 grouping in a multivariate setting for outcome modeling in patients with clear cell renal cell carcinoma.
SO - J Urol 2002 Jul;168(1):56-60
AD - Department of Urology, and Section of Biostatistics, Mayo Clinic, Rochester, Minnesota, USA.
PURPOSE: Lymphadenectomy, especially extended lymphadenectomy, is not commonly performed in patients undergoing a radical nephrectomy for clear cell renal cell carcinoma. Surgeons may sample suspicious regional lymph nodes, but the lymph node status of many patients with renal cell carcinoma remains unknown, termed stage pNx. Outcome models based on large institutional reviews have been criticized for grouping stages pNx and pN0 cases because of concern that the pNx category may include unrecognized stages pN1/pN2 disease. We evaluated cancer specific survival differences in patients with clear cell renal cell carcinoma and a lymph node stage of pNx, pN0 or pN1/pN2. MATERIALS AND METHODS: We searched the registry at our institution for patients who underwent radical nephrectomy for clear cell histology renal cell carcinoma between 1970 and 1998. Those with distant metastases at surgery were excluded from study. Clinical features obtained from the medical record included age at surgery, history of tobacco use, hypertension and symptomatic disease at presentation. A single urological pathologist reviewed all tumor specimens for nuclear grade, tumor necrosis, surgical margin status, 1997 tumor stage and lymph node status. These features were compared in patients with stages pNx and pN0 tumors. Cox proportional hazards models were used to compare cancer specific survival in univariate fashion, and after adjusting for tumor stage and grade. RESULTS: The study cohort consisted of 1,535 patients with sporadic, unilateral clear cell renal cell carcinoma who underwent radical nephrectomy. There were 600 patients (39%) with stage pNx, 870 (57%) with stage pN0 and 65 (4%) with stages pN1/pN2 tumors. At an average of 4.2 years after surgery 414 patients died of renal cell carcinoma. On univariate analysis patients with stage pN0 tumors were significantly more likely to die of renal cell carcinoma than those with stage pNx tumors (risk ratio 1.40, 95% confidence interval 1.12 to 1.75, p = 0.003). However, after adjusting for tumor stage and nuclear grade the difference in outcome for stages pNx and pN0 tumors was not statistically significant (risk ratio 1.07 95% confidence interval 0.85 to 1.34, p = 0.583). Patients with stage pNx disease were significantly less likely to be symptomatic at presentation (p = 0.002), have tumors that were less than 5 cm. (p <0.001) and of lower stage (p <0.001) and grade (p = 0.005), and to have tumors with necrosis (p = 0.024) than patients with stage pN0 disease. CONCLUSIONS: Combining stages pNx and pN0 cases to create outcome prediction models after radical nephrectomy for clear cell renal cell carcinoma is appropriate in a multivariate setting that includes tumor stage and grade. Clinical features available preoperatively and during surgery can help guide the decision to perform limited lymph node sampling. When the tumor is 5 cm. or greater, shows pathological necrosis or is advanced grade 3 or 4, lymph node sampling adds little prognostic information.
UI - 12019174
AU - Esteban-Barragan MA; Avila P; Alvarez-Tejado M; Gutierrez MD;
TI - Garcia-Pardo A; Sanchez-Madrid F; Landazuri MO Role of the von Hippel-Lindau tumor suppressor gene in the formation of beta1-integrin fibrillar adhesions.
SO - Cancer Res 2002 May 15;62(10):2929-36
AD - Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid (UAM), Diego de Leon 62, 28006 Madrid, Spain.
The von Hippel-Lindau tumor suppressor gene (VHL) is absent or inactivated in the VHLcancer syndrome and in most sporadic renal cancers. VHL is requiredfor the assembly of a proper extracellular fibronectin matrix, although the exact mechanism remains unknown. In this report, we demonstrate that 786-O renal cancer cells are unable to organize an adequate matrix even in the presence of an excess of exogenous fibronectin. Because the formation of integrin fibrillar adhesions plays a pivotal role in the organization of extracellular fibronectin, we next examined the expression and subcellular distribution of integrins in VHL- cells and their wild-type VHL stably transfected counterparts. The levels of beta1 and alphav integrins were increased in VHL- cells when compared with VHL+ transfectants. Early after plating, both VHL+ and VHL- cells were capable of assembling classic "patch-like" alphav focal contacts. As the culture advanced and cells became confluent, alphav integrins partly relocated to the intercellular junctions in VHL+ transfectants, which then developed large beta1 fibrillar-type adhesions and anchored firmly to the substrate. In contrast, confluent VHL- cells were unable to assemble beta1 fibrillar adhesions, and alphav focal contacts remained unchanged at all stages of the culture. Exogenous activation of beta1 integrins with either divalent cations or activating antibodies partly restored the capability of VHL- cells to assemble beta1 fibrillar adhesions and fibronectin fibers. Finally, pulse-chase studies of metabolically labeled 786-O cells revealed that the maturation of the common beta1-integrin chain was delayed in VHL- cells when compared with VHL+ cells. Our results show that VHL is an important regulator of integrins and is essential for the formation of beta1 fibrillar adhesions. These findings help to explain the abnormal extracellular matrix organization and increased motility of VHL- renal cancer cells.
UI - 12019178
AU - Turner KJ; Moore JW; Jones A; Taylor CF; Cuthbert-Heavens D; Han C; Leek
TI - RD; Gatter KC; Maxwell PH; Ratcliffe PJ; Cranston D; Harris AL Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation.
SO - Cancer Res 2002 May 15;62(10):2957-61
AD - Imperial Cancer Research Fund Molecular Oncology Laboratory and Angiogenesis Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
The von Hippel-Lindau tumor suppressor protein acts as the substrate recognition component of a ubiquitin E3 ligase that targets hypoxia-inducible factor (HIF)-alpha subunits for proteolysis. Stabilization of HIF-alpha subunits has been described in VHL-defective cell lines, leading to HIF activation and up-regulation of hypoxia-inducible mRNAs. Mutations of the von Hippel-Lindau tumor suppressor protein are found in most clear cell renal cell carcinomas (CC-RCCs) but not other renal tumors, raising a question about the importance of activation of the HIF pathway in CC-RCC development. To address this question, we have examined the expression of HIF-alpha subunits in 45 primary renal tumors and related this to tumor subtype, the presence of VHL mutations, and measures of angiogenesis. We show that HIF-alpha is up-regulated in the majority of CC-RCCs, and that the pattern of expression is biased toward the HIF-2alpha isoform. Expression of HIF-alpha proteins was associated significantly with up-regulation of VEGF mRNA and protein and increased microvessel density. Up-regulation of HIF-alpha in CC-RCC was found to involve increased mRNA as well as protein expression, suggesting that both VHL-dependent and VHL-independent mechanisms are involved. These results suggest that activation of the HIF pathway is functionally important in CC-RCC development and might provide a new therapeutic target.
UI - 12049011
AU - Csekeo A; Fawzi Sel-T
TI - [Surgical treatment for metastatic renal cell tumors of the lung]
SO - Magy Seb 2002 Apr;55(2):73-6
AD - Orszagos Koranyi Tbc es Pulmonologiai Intezet Mellkassebeszeti Osztaly, 1529 Budapest. email@example.com
Number of resection for lung metastasis in Hungary is low, however surgery provides benefit for patients using an integrated oncological therapeutical protocol. The authors give a retrospective analysis of 57 patients operated on for metastatic renal cell tumor to the lung. Metastases were discovered most frequently by x-ray picture of an accidental investigation or screening at symptom-free patients and in 32 cases solitary and in 25 cases multiple deposits were proved. After selection's protocol 20 patients underwent lobectomy and 32 ones wedge resection while in 5 cases only biopsy was done. Out of 52 cases 33 complete resections were performed and in 9 cases incomplete resection was carried out. The cumulative five-year survival time was 35%, following complete resection 45%. If DFI was longer than 12 months, survival was observed 38% at five year. SUMMARY: On basis of our experience after surgery of metastatic renal cell tumors to the lung might expect favourable survival which is significantly better after complete resection of lung metastasis and after longer than 12 months DFI.
UI - 12070267
AU - Shenouda A; Douglas SA; Ohlstein EH; Giaid A
TI - Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma.
SO - J Histochem Cytochem 2002 Jul;50(7):885-9
AD - The Montreal General Hospital, McGill University, Montreal, Quebec, Canada.
Human urotensin-II (U-II) is a cyclic 11-amino-acid residue peptide with a wide range of vasoactive properties dependent on the anatomic site and the species studied. The purpose of this study was to determine the localization of human U-II in normal human kidneys and in renal carcinoma. Normal human kidneys (n=11) and eight cases of clear-cell carcinoma were immunostained with a polyclonal antibody to human U-II. In normal human kidneys, U-II was mostly present in the epithelial cells of tubules and ducts, with greater intensity in the distal convoluted tubules. Moderate U-II immunoreactivity was seen in the endothelial cells of renal capillaries, but only focal immunoreactivity was found in the endothelial cells of the glomeruli. No staining was found in the veins. All tumors expressed moderate U-II immunoreactivity in the cancer cells and vasculature. Here we demonstrate abundant expression of U-II in normal human kidneys and renal carcinoma. These findings suggest that the vasoactive and growth-mediator peptide U-II may contribute to the pathophysiology of the human renal system.
UI - 11337362
AU - Young AN; Amin MB; Moreno CS; Lim SD; Cohen C; Petros JA; Marshall FF;
TI - Neish AS Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers.
SO - Am J Pathol 2001 May;158(5):1639-51
AD - Department of Pathology, Emory University School of Medicine, Atlanta, USA.
The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.
UI - 11702121
AU - Helenon O; Correas JM; Balleyguier C; Ghouadni M; Cornud F
TI - Ultrasound of renal tumors.
SO - Eur Radiol 2001;11(10):1890-901
AD - Department of Radiology, Necker Hospital, 149 rue de Sevres, 75743 Paris, France. firstname.lastname@example.org
Despite the limitations of US in providing a complete evaluation of renal tumors before treatment planning, initial screening, characterization of renal masses and staging of RCCs can benefit from some recent advances of the technique. One of the most relevant clinical benefits of US is the increased early detection of RCCs. Recent technical improvement of gray-scale imaging has increased US performance in the detection of small renal tumors. Combined gray-scale and color Doppler US findings may strongly suggest the histopathologic nature of a renal tumor with respect to the size, the US attenuation characteristics, and the vascular distribution of the lesion. Ultrasound contributes additional diagnostic information for differential diagnosis of some renal masses that remain equivocal at CT, including: atypical cystic lesions; solid renal tumors with poor vascularity; and angiomyolipomas with minimal fat component. Ultrasound also may provide additional diagnostic information over CT in selected cases of RCCs with venous invasion. In addition to some diagnostic and therapeutic procedures that can benefit from US guidance, intraoperative US remains the only available tool that enables to ensure renal-parenchymal-sparing surgery.
UI - 11702145
AU - Walter C; Heindel W; Kruessell M; Kugel H; Jung G; Gindele A
TI - Fast sequences with fat suppression in breath-hold mode: new standard in contrast-enhanced T1-weighted MR imaging of renal tumors?
SO - Eur Radiol 2001;11(10):2092-8
AD - Department of Diagnostic Radiology, University of Cologne, 50924 Koln, Germany. email@example.com
Our purpose was to analyze detection, diagnostic characterization, and staging of renal solid lesions using different fast T1-weighted sequences with fat suppression in breath-hold mode compared with a gradient-echo sequence after contrast application. Twenty-five patients with focal renal lesions were examined with a T1-weighted ultrafast turbo spin-echo (UTSE) sequence with frequency selective fat suppression (SPIR), two different segmented echo-planar imaging (EPI) sequences - a spin-echo and a gradient-echo echo-planar sequence (SE-, FFE-EPI) combined with SPIR and a gradient-echo (fast field echo, FFE) sequence in a prospective study. The images of all sequences were visually evaluated and in addition to qualitative evaluation the contrast-to-noise ratio (CNR) for cyst and solid lesions was measured. Among the different T1-weighted sequences, the best detection and characterization of renal solid lesions were obtained with the UTSE SPIR and the SE-EPI sequence (sensitivity: 100 and 75%, respectively; specificity: 90 and 75%, respectively). The FFE and FFE-EPI sequences showed lower sensitivity (86%) and the same specificity (75%). The staging of renal tumors was best achieved with the UTSE SPIR and SE-EPI sequence (84 and 73%, respectively). The staging was correct in only 47% and 58 for the FFE and FFE-EPI sequences, respectively. The investigated sequences showed no significant differences in CNR. The combination of fat suppression and breath-hold mode improves detection, characterization, and staging of renal lesions. The UTSE SPIR and SE-EPI sequence in breath-hold mode showed specific image artifacts, but offered high sensitivity and specificity for detection and characterization of renal lesions compared with the FFE sequence. The results of this study suggest, for T1-weighted imaging of renal tumors, use of UTSE or SE-EPI sequences with fat suppression in breath-hold mode for renal imaging.
UI - 11684839
AU - Mickisch G; Carballido J; Hellsten S; Schulze H; Mensink H; European
TI - Association of Urology Guidelines on renal cell cancer.
SO - Eur Urol 2001 Sep;40(3):252-5
AD - Erasmus University Rotterdam, The Netherlands. firstname.lastname@example.org
OBJECTIVES: On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and Follow-Up of Renal Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts on renal cell carcinoma (RCC). RESULTS: RCC is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There is no risk factor established and the current TNM system (UICC, 1997) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent, incidental discovery constitutes already a majority of cases. Diagnosis is established by ultrasound and abdominal CT, extension assessment in routine cases is done by chest X-ray. Additional examinations may be required in select cases. The therapy of choice in organ-confined RCC is surgery. Radical tumour nephrectomy is considered as a standard. Efficacy and side-effects of organ-sparing surgery, lymphadenectomy and inclusion/omission of ipsilateral adrenalectomy in selected cases is a matter of ongoing clinical research. In metastatic cases, tumour nephrectomy should only be considered in the context of modern systemic immunotherapy. A follow-up at regular intervals is recommended because certain cases of recurrences may be candidates for surgery and/or immunomodulating therapy. CONCLUSION: A rise in incidence, improved diagnostic procedures, and evolving multimodality therapeutic concepts justify the need for rational guidelines on this most challenging urologic malignancy.
UI - 11684849
AU - Huguet-Perez J; Palou J; Millan-Rodriguez F; Salvador-Bayarri J;
TI - Villavicencio-Mavrich H; Vicente-Rodriguez J Upper tract transitional cell carcinoma following cystectomy for bladder cancer.
SO - Eur Urol 2001 Sep;40(3):318-23
AD - Department of Urology, Fundacio Puigvert, Barcelona, Spain.
PURPOSE: We assessed the incidence of upper urinary tract tumors (UUTTs) after cystectomy for invasive or superficial transitional cell carcinoma (TCC) of the bladder. The risk factors, patients' characteristics and evolution of those who developed UUTTs are analyzed. MATERIALS AND were performed for TCC of the bladder: in 469 instances (82.5%) due to invasive tumor (T2-T4), and in 99 cases (17.5%) for superficial tumor (Ta, T1, Tis). All patients were followed for at least 5 years or until death. A retrospective study of patients who developed UUTTs has been performed. A revision of bladder tumor and UUTT characteristics, and the intervals between both is also evaluated. RESULTS: 26 patients (4.5%) developed UUTTs: 11 of the 99 patients cystectomized for superficial TCCs (11.1%); 6 of the 392 patients with primary invasive TCC (1.5%), and 9 of the 77 (11.6%) patients with invasive tumors and a prior history of superficial TCC. The interval to the development of UUTT was higher after cystectomy for superficial tumor. TCCs of the bladder that subsequently developed UUTTs were high grade in 84%, multifocal in 80%, or had carcinoma in situ in 65%, tumor in the prostatic urethra in 52%, and involvement of the distal ureter in 57%. Twenty-two UUTTs (84%) were located in the calyces or the renal pelvis, 3 were bilateral (11.5%), 14 multiple (58%) and 4 superficial (16%). With a median follow-up time of 18 (range 3-103) months, 14 patients (53.8%) died of tumor, 2 were alive with disease, 2 were lost for follow-up, and 8 (30%) were alive and free of disease. CONCLUSIONS: We found that patients cystectomized for superficial or invasive TCC with a prior history of superficial TCC have a higher incidence of UUTTs. These cases require follow-up with annual urography or loopography.
UI - 11684851
AU - Junker K; Weirich G; Moravek P; Podhola M; Ilse B; Hartmann A; Schubert
TI - J Familial and sporadic renal oncocytomas--a comparative molecular-genetic analysis.
SO - Eur Urol 2001 Sep;40(3):330-6
AD - Department of Urology, Jena, Germany. email@example.com
OBJECTIVES: Genetic causes of sporadic and familial renal oncocytomas are not known. We analyzed these tumors genetically in order to detect tumor-specific chromosome alterations. METHODS: DNA from 26 sporadic and 31 familial renal oncocytomas were screened by comparative genomic hybridization according to standard protocols including degenerate oligonucleotide-primed PCR. RESULTS: Chromosome alterations were detected in 19/26 sporadic (73%) and in 4/31 familial renal oncocytomas (13%). Partial or complete losses of chromosome 1 were most frequently found in both sporadic (15/26) and familial tumors (2/4). Less frequently, loss of chromosome 14 (3/26) was detected in sporadic renal oncocytomas as well as losses of 2p, 2q, 4q, 10 and 18 and gains of 1q and 17q in individual sporadic tumors. Inter-tumor variation of chromosome aberrations was prominent in 1 patient, where 1 tumor showed gains of chromosomes 5, 6q, 7, 10p, 12 and 13q, whereas the second tumor exhibited gains of chromosomes 5 and 7 and loss of 10q. In contrast to sporadic renal oncocytomas, most familial tumors (87%) were devoid of chromosome instabilities. CONCLUSION: Our results demonstrate that partial or complete loss of chromosome 1 is the most common alteration in renal oncocytomas, sporadic and familial. However, chromosome changes are much rarer in familial than in sporadic renal oncocytomas.
UI - 11684852
AU - Spahn M; Portillo FJ; Michel MS; Siegsmund M; Gaa J; Alken P; Junemann
TI - KP Color Duplex sonography vs. computed tomography: accuracy in the preoperative evaluation of renal cell carcinoma.
SO - Eur Urol 2001 Sep;40(3):337-42
AD - Department of Urology, Klinikum Mannheim GmbH, University of Heidelberg, Mannheim, Germany.
PURPOSE: Accurate imaging is essential for correct operative planning and successful surgical intervention in renal cell carcinoma (RCC). Our objective was the comparison of color duplex sonography with spiral computed tomography (CT) and surgical-pathological findings in the evaluation of renal masses to determine tumor localization, size, tumor thrombus extent and lymph node metastases. METHODS: We evaluated 60 patients with a renal mass in a prospective study. Both color duplex sonography and CT were performed by different investigators without knowledge of the supposed diagnosis. The color Doppler findings were compared to CT and surgical pathological findings. RESULTS: The sensitivity of color duplex sonography in the detection of RCC and lymph node metastases is comparable to that of CT (100%). Color duplex sonography was superior in the detection of renal vein involvement. Color duplex sonography alone allowed correct planning of the surgical procedure without intraoperative changes in all patients. CONCLUSION: Duplex sonography provides exactly the same information as CT. Although duplex sonography is less expensive with lower exposure to radiation, most surgeons will still probably demand CT for diagnosis, especially as this method is unerring and duplex sonography highly depends on the expertise of the person using it.
UI - 12036906
AU - Bindra RS; Vasselli JR; Stearman R; Linehan WM; Klausner RD
TI - VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.
SO - Cancer Res 2002 Jun 1;62(11):3014-9
AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell