Surgical revascularization for renal artery disease: current status.
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Age Factors↗
Biomedical subjects
Andrew C Novick
Publications and source records attributed to Andrew C Novick.
Mechanisms of renal ischaemic injury and their clinical impact.
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Cell Adhesion Molecules↗
Effects of resveratrol on gene expression in renal cell carcinoma.
Studies have shown that Resveratrol (RE) can inhibit cancer initiation, promotion, and progression. However the gene expression profile in renal cell carcinoma (RCC) in response to RE treatment has never been reported. To understand the potential anticancer effect of RE on RCC at molecular level, we profiled and analyzed the expression of 2059 cancer-related genes in a RCC cell line RCC54 treated with RE. Biological functions of 633 genes were annotated based on biological process ontology and clustered into functional categories. Twenty-nine highly differentially expressed genes in RE treated RCC54 were identified and the potential implications of some gene expression alterations in RCC carcinogenesis were identified. RE was also shown to inhibit cell growth and induce cell death of RCC cells. The expression alterations of selected genes were validated using reverse transcription polymerase chain reaction. In addition, the gene expression profiles under different RE treatments were analyzed and visualized using singular value decomposition. The findings from this study support the hypothesis that RE induces differential expression of genes that are directly or indirectly related to the inhibition of RCC cell growth and induction of RCC cell death. In addition, it is apparent that the gene expression alterations due to RE treatment depend strongly on RE concentration. This study provides a general understanding of the overall genetic response of RCC54 to RE treatment and yields insights into the understanding of the cancer preventive mechanism of RE in RCC.
Angiogenesis Inhibitors↗
Innovations and challenges in renal cancer: consensus statement from the first international conference.
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Humans↗
Laparoscopic and partial nephrectomy.
Radical nephrectomy is the gold standard curative operation for patients with localized renal cell carcinoma (RCC). Since its introduction in 1990, laparoscopic radical nephrectomy is being increasingly done at numerous institutions worldwide. In the hands of experienced laparoscopic urological surgeons and with adherence to established principles of open radical nephrectomy, laparoscopic radical nephrectomy is now a standard of care for patients with T1-3a N0 M0 RCC. Intermediate-term outcome data indicate equivalent cancer-free survival to open radical nephrectomy in such cases. Nephron-sparing surgery (NSS) is now an established approach for patients with localized RCC when there is a clinically relevant need to preserve renal function. NSS is also indicated in patients with a single, small, unilateral, localized RCC when the opposite kidney is completely normal. The technical success rate with NSS for RCC is excellent, and long-term patient survival free of cancer is comparable with that obtained after radical nephrectomy. We recently reviewed the results of NSS in 107 patients with localized sporadic RCC treated at the Cleveland Clinic before 1988 who were followed up for a minimum of 10 years. Long-term preservation of renal function was achieved in 93% of patients, and the 10-year cancer specific survival rate was 73%. Although open surgical partial nephrectomy remains the gold standard for nephron-sparing treatment of RCC, laparoscopic partial nephrectomy is now available in selected cases. The optimal indications for laparoscopic NSS are in patients with a relatively small and peripheral renal tumor. In such cases, laparoscopic NSS is proving to be an effective, minimally invasive therapeutic approach with respect to renal functional outcome, with additional advantages of reduced postoperative narcotic use, earlier hospital discharge, and a faster convalescence. The laparoscopic approach is associated with longer warm renal ischemia time, more major intraoperative complications, and more postoperative urological complications. Continued efforts are required to develop laparoscopic renal hypothermia techniques and to facilitate intrarenal suturing while minimizing the warm ischemia time.
Carcinoma, Renal Cell↗
Differential protein profiling in renal-cell carcinoma.
Characterizing the alterations of protein expression in cancer cells can be very useful in providing insight into the changes in the functional pathways and thus the fundamental mechanisms of cancer development at the molecular level. In this study, we profiled protein expressions in eleven pairs of primary cell cultures derived from renal-cell carcinoma (RCC) tissues and patient-matched normal kidney tissues utilizing two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Together with the immunoblot analysis of proteins from the RCC tissues, the study also demonstrated that the alterations of protein expression observed in RCC primary cell cultures reflected those observed in the original RCC tissues. We analyzed the expression profiles and identified proteins differentially expressed in RCC primary cell cultures by 2-D PAGE and mass spectrometry (MS). We found sixteen proteins were overexpressed and seven proteins underexpressed in RCC. The deregulated expressions of proteins include those involved in metabolism, cellular morphology, heat shock response, cell growth, etc. Overexpression of three proteins, alphabeta-crystallin, manganese superoxide dismutase (MnSOD), and annexin IV, most commonly observed in primary RCC cell cultures, were also observed by immunoblot analysis of proteins from the RCC tissues from which the primary cell cultures were derived. Semi-quantitative reverse transcription (RT)-polymerase chain reaction (PCR) analysis revealed the direct correlation between deregulated gene expression and the corresponding protein abundance in two of the three most commonly upregulated proteins we found in RCC.
Annexin A4↗
Laparoscopic nephrectomy for large renal arteriovenous malformation.
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Aortography↗
Renal cell cancer in solitary kidney after donor nephrectomy.
The occurrence of renal cell carcinoma in the solitary remnant kidney after donor nephrectomy is rare and, to our knowledge, has not been previously reported. We encountered 2 such patients in whom cancer occurred 19 and 40 years after the donation. Both patients underwent successful partial nephrectomy for the tumor using two different techniques.
Carcinoma, Renal Cell↗
Laparoscopic versus open cytoreductive nephrectomy for metastatic renal cell carcinoma.
OBJECTIVES: To compare the outcomes of those patients who underwent laparoscopic versus open cytoreductive nephrectomy. Cytoreductive nephrectomy before systemic therapy has been shown to offer a survival advantage compared with systemic therapy alone for metastatic renal cell carcinoma. METHODS: We reviewed the outcomes of all patients who underwent either open or laparoscopic cytoreductive nephrectomy between 2000 and 2003. The inclusion criteria included patients with tumors 15 cm or less without local invasion, venous involvement, or bulky local adenopathy who had concurrent metastatic disease. A total of 64 patients (22 in the laparoscopic group and 42 in the open group) fulfilled these criteria. The parameters measured were age, tumor size, operative time, estimated blood loss, complications, length of hospital stay, percentage of patients receiving systemic therapy, and the interval to the start of systemic therapy. Kaplan-Meier survival estimates were compared. RESULTS: Patients who underwent laparoscopic cytoreductive nephrectomy had a shorter length of stay (2.3 versus 6.1 days) and less operative blood loss (288 versus 1228 mL) than those who underwent open nephrectomy. Patients in the laparoscopic group received systemic therapy sooner after surgery (36 versus 61 days) than those in the open group. The Kaplan-Meier survival estimates were similar for both groups, with a 1-year survival rate of 61% in the laparoscopic group and 65% in the open group. CONCLUSIONS: With judicious patient selection, laparoscopic cytoreductive nephrectomy can be performed safely, with minimal morbidity, and may shorten the interval from nephrectomy to the start of systemic therapy.
Blood Loss, Surgical↗
Factors related to delayed graft function after laparoscopic live donor nephrectomy.
PURPOSE: Delayed graft function after live donor transplantation affects 5% to 10% of recipients regardless of procurement technique. This delay in function is associated with an increased risk of rejection and decreased graft survival. In the present study we critically assess allograft recovery to identify the risk factors related to delayed graft function. MATERIALS AND METHODS: We retrospectively reviewed donor and recipient medical records from 100 consecutive laparoscopic live donor nephrectomies from August 1997 to October 2001. Four criteria were used to classify delayed graft function: I) requirement of dialysis in postoperative week 1, II) creatinine 2.5 mg/dl or greater at postoperative day 5, III) time to half peak activity (mercaptoacetyltriglycine renal scan) at postoperative day 5 greater than 12.2 minutes (normal range 1 to 12.2) and IV) time to peak activity (mercaptoacetyltriglycine renal scan) at day 5 greater than 6.5 minutes (normal range 2.1 to 6.5). Patients could qualify for multiple outcome categories. Patients who did not match any of these criteria were classified as having normal renal function (outcome 0). RESULTS: The number of patients in the delayed graft function categories were 5 with outcome I, 14 with outcome II, 39 with outcome III and 24 with outcome IV. There were 23 patients represented in more than 1 category and 59 patients were classified as having normal function. Recipient age, donor/recipient gender relationship, unrelated highly mismatched donors and cold/total preservation time were identified as risk factors related to impaired early renal function recovery. None of the variables related to the laparoscopic technique itself represented risk factors for delayed graft function. CONCLUSIONS: Female donor kidneys into male recipients and highly HLA mismatched donors represent factors that may be controlled by donor selection when feasible. All attempts should be made to decrease cold ischemia time and, therefore, total preservation time. Prolonged carbon dioxide pneumoperitoneum, warm ischemia time, renal artery length or use of right kidney did not adversely affect the functional outcome of the allografts procured laparoscopically.
Adult↗
The influence of various maintenance immunosuppressive drugs on lymphocele formation and treatment after kidney transplantation.
PURPOSE: We compared the incidence of lymphocele formation and treatment in kidney transplant recipients given 3 immunosuppressive drug regimens. MATERIALS AND METHODS: Consecutive series of adult kidney only recipients, including group 1-152 who received sirolimus/mycophenolate mofetil (MMF)/prednisone (P), group 2-168 who received cyclosporine/MMF/P and group 3-193 who received cyclosporine/azathioprine/P, were analyzed for post-transplantation lymphocele formation. All available records and imaging studies were reviewed, such as ultrasound, computerized tomography, magnetic resonance imaging etc, for peritransplant fluid collections greater than 2.5 cm. Demographic characteristics and the risk factors for lymphocele were compared in these 513 recipients using univariate and multivariate analysis. RESULTS: The overall incidence of lymphocele formation was 174 of 513 cases (33.9%) and the incidence of treated lymphoceles was 81 of 513 (15.7%). In groups 1 to 3 the incidence was 45.5%, 33.9% and 24.7%, respectively. These differences were significantly higher in group 1 vs groups 2 or 3 (p = 0.014) but they were not significantly different between groups 2 and 3. Similarly the incidence of treated lymphoceles was 23%, 12.5% and 12.9%, respectively. Findings were again statistically higher in group 1 vs groups 2 and 3 (p = 0.003) but not statistically significant between groups 2 and 3. A greater number of group 1 patients required surgical interventions compared with those in groups 2 and 3 (13.8% vs 4.7% and 4.8%, respectively, p = 0.019). In addition, acute rejection (p = 0.001) and body mass index greater than 32 (p = 0.02) were significant risk factors on multivariate analysis. CONCLUSIONS: The combination of sirolimus/MMF/P, obesity with a body mass index of greater than 30 kg/m and acute rejection are independent risk factors for lymphocele formation and treatment after kidney transplantation. Patients should be counseled and consideration should be given to prophylactic measures in this higher risk renal transplant population.
Adult↗
Laparoscopic radical nephrectomy for large (greater than 7 cm, T2) renal tumors.
PURPOSE: Laparoscopic radical nephrectomy has emerged as a standard of care in appropriate candidates with clinical stage T1 renal tumors (7 cm or less). Herein we present our experience with laparoscopic radical nephrectomy for clinical stage T2 tumors (greater than 7 cm). MATERIALS AND METHODS: Patients undergoing laparoscopic radical nephrectomy between September 1997 and July 2003 were retrospectively subdivided into group LAPT1-166 with tumor size 7 cm and group LAPT2-65 with tumor size greater than 7 cm. Also, group LAPT2 was compared with a group of 34 contemporary, comparable patients undergoing open radical nephrectomy for tumor greater than 7 cm (group OPENT2). RESULTS: Compared with group LAPT1, group LAPT2 had younger patients, larger tumors and greater blood loss (100 vs 200 ml) (each p <0.001). Importantly operative time, analgesic requirements, hospital stay, and convalescence and complication rates were comparable. Group LAPT2 and group OPENT2 patients had similar sized tumors (9.2 and 9.9 cm, respectively) but shorter operative time (p = 0.03), lesser blood loss (p <0.001), shorter hospital stay (p <0.001) and more rapid convalescence (p = 0.02) occurred in LAPT2. CONCLUSIONS: Laparoscopic radical nephrectomy for stage T2 renal masses (greater than 7 cm) is feasible and efficacious. Laparoscopic nephrectomy offers the advantages of decreased blood loss, shorter hospital stay and more rapid recovery over open radical nephrectomy for comparable tumors greater than 7 cm. Although surgical outcomes are comparable with laparoscopic radical nephrectomy for smaller tumors (7 cm or less), adequate laparoscopic experience is necessary before performing radical nephrectomy for large T2 tumors.
Aged↗
Fate of donor kidney: laparoscopic versus open technique.
PURPOSE: Laparoscopic donor nephrectomy (LDN) is an increasingly accepted modality for procuring donor kidneys for transplantation. We analyzed and compared the short and long-term outcomes of living transplant allografts from kidneys procured by laparoscopic or open donor (ODN) technique and managed with a single immunosuppression regimen in each group. MATERIALS AND METHODS: Records of recipients who underwent living (laparoscopic or open) donor nephrectomy were reviewed from August 1999 to July 2001 for LDN and from January 1994 to December 1999 for ODN. Patients included were on a single immunosuppression regimen particular to each group. Sirolimus, mycophenolate mofetil and prednisone were given to the LDN group, and calcineurin inhibitor (FK-506 or cyclosporine), mycophenolate mofetil and prednisone were given to the ODN group. Excluded from study were patients with prior kidney transplant or patients not receiving immunosuppression as previously described. Also excluded from study were patients lost to followup before 1 year. Data were retrieved retrospectively from case notes or from the transplant database and analyzed using SAS software (SAS Institute, Cary, North Carolina). RESULTS: A total of 71 patients from the LDN group and 60 patients from the ODN group qualified for the study. Demographic data are comparable in both groups except for the significantly longer followup in the ODN group. Serum creatinine was 2.2 and 1.8 mg/dl at postoperative day 4, 1.3 and 1.3 mg/dl at day 10, and 1.3 and 1.4 mg/dl at 1 month in the LDN and ODN groups, respectively. Time to achieve nadir serum creatinine was 8.7 versus 6.6 days for LDN and ODN groups, respectively (p = not significant). Delayed graft function was noted in 5 of 71 (7%) in the LDN group and 3 of 60 (5%) in the ODN group (p = 0.5). In the LDN group 13 (18%) patients had a serum creatinine of greater than 1.5 mg/dl at postoperative day 30 compared to 6 (10%) in the ODN group (p = 0.06). Mean serum creatinine at 1 year was lower for LDN recipients (p = not significant). But at last followup this difference became statistically significant in favor of LDN. Mean followup was 939 versus 2,046 days for LDN versus ODN, respectively (p <0.0001). Recipient mean hospital stay was 5.2 versus 6.7 days for LDN versus ODN, respectively (p = 0.08). There were 8 of 78 (10.2%) episodes of acute rejection in the LDN group compared to 22% in the ODN group (p = 0.08). The complication rate (ureteral vascular, lymphocele, acute rejection and wound) was 11% in LDN compared to 15% in the ODN group. Long-term graft function, graft survival and patient survival in the LDN group were comparable to the ODN group. CONCLUSIONS: Early graft recovery is slower in LDN allografts, although not statistically significant, but long-term function in the LDN group is significantly better compared to the ODN group. Laparoscopic donor kidneys take longer to achieve nadir serum creatinine, but this does not influence long-term outcome and results.
Adult↗
Laparoscopic cytoreductive nephrectomy for metastatic renal cell carcinoma.
OBJECTIVE: To critically analyse the results of laparoscopic cytoreductive surgery for renal cell carcinoma (RCC), as phase III evidence supports cytoreductive nephrectomy before immunotherapy, and there is an overall shift towards minimally invasive renal surgery for this disease. PATIENTS AND METHODS: Since October 2000, 22 patients were treated by laparoscopic cytoreductive nephrectomy for metastatic RCC (group 1). All patients had radiological evidence of metastatic disease, with biopsy confirmation in 10. To put the results into perspective, 25 consecutive contemporary patients with large organ-confined nonmetastatic RCC (>7 cm, clinical stage T2) undergoing laparoscopic radical nephrectomy (group 2) were compared retrospectively. The baseline demographics were comparable between the groups. RESULTS: The mean tumour size was 8 cm in group 1 and 9.6 cm in group 2 (P = 0.07). Variables during and after surgery were comparable between the groups, with a mean operative duration of 3.1 vs 3.2 h (P = 0.82), blood loss of 285 vs 308 mL (P = 0.79), complications in two vs eight (P = 0.08), morphine sulphate equivalent requirements of 51.7 vs 44.1 mg (P = 0.1) and a median length of hospital stay of 1.7 vs 1.6 days (P = 0.68). In group 1 the median (range) time to immunotherapy was 35 (13-136) days. CONCLUSIONS: Laparoscopic cytoreductive nephrectomy is safe and effective in selected patients. Currently the procedure is offered to candidates eligible for immunotherapy and with tumours of < or = 15 cm, and no evidence of adjacent organ invasion or inferior vena caval thrombus. Significant perihilar adenopathy and numerous parasitic vessels can increase the complexity of the surgery. Adequate laparoscopic experience is necessary.
Carcinoma, Renal Cell↗
Analysis of changes in attenuation of proven renal cysts on different scanning phases of triphasic MDCT.
OBJECTIVE: The purpose of this study is to document changes in attenuation values on triphasic MDCT of histologically or surgically proven cystic renal lesions. MATERIALS AND METHODS: A retrospective study of all renal lesions greater than 1 cm that underwent triphasic MDCT was performed in 90 patients before partial nephrectomy. Three reviewers independently measured the mean attenuation of all lesions in three phases (unenhanced, corticomedullary, and parenchymal) in a blinded retrospective fashion. Forty-three lesions identified at CT in 27 patients had pathologic or surgical confirmation as cysts (fluid-filled lesions). Mean change in attenuation between phases was calculated and correlated with size, unenhanced density, and percentage of the lesion exophytic from renal parenchyma. All scans were obtained after 150 mL of nonionic contrast material was injected at 3 mL/sec. Scanning delays were 30-40 sec (corticomedullary phase) and 120 sec (parenchymal phase). RESULTS: The mean change in attenuation coefficient of the cysts from the unenhanced to the parenchymal phase was -1.8 H (SD, +/- 4.4 H); from the unenhanced to the corticomedullary phase was -2.3 H (+/- 3.9 H); and from the corticomedullary to the parenchymal phase was 0.6 H (+/- 4.2 H). No cyst increased more than 10 H between the unenhanced and the parenchymal phases; more than 95% of cysts increased less than 8 H between any scanning phases. No significant difference was seen in enhancement related to lesion size (p > 0.054), unenhanced attenuation (p > 0.255), or percentage of the lesion that was exophytic (p > 0.124). CONCLUSION: The attenuation coefficient of a cystic renal lesion increased by no more than 10 H among the unenhanced, corticomedullary, and parenchymal phase scans.
Contrast Media↗
F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma.
PURPOSE: We conducted a study to evaluate the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of distant metastases from renal cell carcinoma (RCC). MATERIALS AND METHODS: Twenty-four patients with histologically proven clear-cell RCC undergoing surgical evaluation for possible resection of recurrent disease were investigated. All patients had suspected distant metastases based on conventional anatomic imaging techniques (computed tomography and magnetic resonance imaging). A total of 36 distant metastatic sites were identified. Pathology for all sites was obtained by biopsy or after surgical resection. RESULTS: Histologically documented distant metastases from RCC were present in 33 sites (21 patients). Overall sensitivity, specificity, and positive predictive value of FDG-PET for the detection of distant metastases from RCC was 63.6% (21 of 33), 100% (three of three), and 100% (21 of 21), respectively. The mean size of distant metastases in patients with true-positive FDG-PET was 2.2 cm (95% CI, 1.7 to 2.6 cm) compared with 1.0 cm in patients with false-negative FDG-PET (95% CI, 0.7 to 1.4 cm; P =.001). CONCLUSION: FDG-PET is not a sensitive imaging modality for the evaluation of metastatic RCC and may not adequately characterize small metastatic lesions. However, positive FDG-PET is predictive for the presence of RCC in lesions imaged, may complement anatomic radiologic imaging modalities, and may alleviate the need for a biopsy in selected situations. A negative FDG-PET, however does not rule out active malignancy.
Adult↗
Chemokine and receptor-gene expression during early and late acute rejection episodes in human cardiac allografts.
BACKGROUND: The expression levels of several chemokine genes in heart allografts correlate with histologic rejection grade. Potential molecular differences between early and late rejection (grade > or =2) episodes were examined by testing chemokine and receptor-gene expression. METHODS: Expression of inducible protein (IP)-10, monokine induced by IFN-gamma (Mig), interferon inducible-T cell alpha chemoattractant (I-TAC), regulated on activation normal T-cell expressed and secreted(RANTES), and their receptors CXCR3 and CCR5 was tested in 60 endomyocardial biopsies from 24 patients using quantitative (Taqman) real-time polymerase chain reaction (PCR). The biopsies were taken in the first 3 months or from the 9th to the 12th month following transplantation. RESULTS: IP-10, Mig, RANTES, CXCR3, and CCR5 expression levels were increased in the later versus earlier biopsies (P< or =0.01) despite no change in histologic rejection-grade status. CONCLUSION These results demonstrate significantly increased expression of T-cell chemoattractants in heart allografts during later rejection when compared with episodes occurring shortly after transplantation. The findings suggest increased intensity of inflammation in rejection occurring at later times posttransplant that are revealed by molecular analyses of the graft.
Acute Disease↗
T-cell mediated induction of allogeneic endothelial cell chemokine expression.
BACKGROUND: The goal of the current study was to test the ability of T cells to stimulate allogeneic endothelial cells to express chemokines, particularly the T-cell recruiting factors monokine induced by interferon-gamma (Mig) and inducible protein (IP)-10. METHODS: Lymph node cells from C57BL/6 (H-2b) recipients of C3H (H-2k) skin grafts or from naïve mice were added to monolayers of C3H-derived endothelial cell line 2F-2B. After 5 or 24 hr, the lymph node cells were removed, and RNA was prepared from the endothelial cells and tested by ribonuclease protection assay or Northern blot hybridization for endothelial cell expression of chemokines. RESULTS: Alloantigen-primed T cells induced endothelial cell expression of regulated on activation normal T-cell expressed and secreted (RANTES), IP-10, Mig, monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta within 5 hr of coculture. In vitro chemotaxis assays demonstrated the production of T-cell chemoattractants by the endothelial cells. With the exception of low levels of monocyte chemotactic protein-1 and RANTES, culture with naïve C57BL/6 lymph node T cells did not induce endothelial cell chemokine expression. Alloantigen-primed CD4 T cells induced endothelial expression of IP-10 and RANTES but none of the other chemokines tested, whereas primed CD8 T cells induced all of the chemokines tested. Expression of IP-10 and Mig was not induced when alloantigen-primed T cells from interferon-gamma deficient recipients of C3H skin grafts were cultured with the endothelial cells. This expression was blocked by addition of intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1 specific antibodies to the cultures. CONCLUSIONS These results demonstrate the ability of alloantigen-primed CD8 T cells to quickly and directly stimulate endothelial cells to express and produce chemokines, including those recruiting T cells.
Animals↗