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Amnon Zisman

Publications and source records attributed to Amnon Zisman.

50 records · Page 3Linked to original sources

Kidney pathology: current classification of renal cell carcinoma.

This report discusses the new cytogenetic classification of renal cell carcinoma (RCC) and its biological and clinical significance. It describes the four major types (clear cell, chromophil, chromophobe, and collecting duct) as well as rarer entities, such as small cell carcinoma, cystic RCC, rhabdoid variant of RCC, and unclassified RCC. Sarcomatoid carcinomas are a diverse group representing high-grade transformation of the other types. In addition to a description of the pathologic findings, there is a discussion of tumor markers and prognostic indicators. The clinical significance of the classification is discussed, with reference to recent reports.

Carcinoma, Renal Cell↗

Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study.

PURPOSE: We determined the efficacy of anesthesia for prostate biopsy by periprostatic lidocaine injection. MATERIALS AND METHODS: A total of 90 consecutive patients undergoing prostate biopsies were randomized into lidocaine and placebo groups of 45 each in double-blind fashion. A 5 ml. dose of 1% lidocaine or 0.9% sodium chloride was injected via 23 gauge needles inserted through the transrectal ultrasound probe working channel and aimed at the prostatic neurovascular bundles bilaterally. Patients completed a symptom questionnaire applying a visual analog scale of 0-none to 10-maximal addressing pre-procedure anxiety, overall pain and discomfort throughout the procedure, pain during biopsy punctures and patient tolerance, as judged by the operator. Student's t test was used to analyze continuous variables and the chi-square test was applied for categorical data. Linear regression was done to determine intervariable influences. RESULTS: The average pain level throughout the procedure was 3.06 in the lidocaine group versus 4.15 in the control group (p = 0.04), while the pain level during biopsy punctures was 1.51 versus 3.98 (p = 0.0001) and patient tolerance was 1.06 versus 1.93 (p = 0.018). The level of discomfort throughout the procedure was lower in the lidocaine group with borderline significance (4.31 versus 5.24, p = 0.077). The lidocaine and control groups were comparable regarding average patient age (65 and 66 years, respectively). Prostate volume was similar in the 2 groups (68.5 versus 63 ml.). The median number of biopsy punctures was 7 and 8, respectively. Cancer was identified in 10 patients (22.2%) per group. CONCLUSIONS: Periprostatic lidocaine injection is an effective method of anesthesia for prostate biopsy.

Aged↗

Unclassified renal cell carcinoma: clinical features and prognostic impact of a new histological subtype.

PURPOSE: We characterized the histopathological features and clinical behavior of unclassified renal cell carcinoma and compared the prognostic outcome in patients with unclassified and conventional (clear cell) renal cell carcinoma. MATERIALS AND METHODS: A total of 31 patients with unclassified renal cell carcinoma are included in the kidney cancer database at our institution. Another 317 matched patients with clear cell carcinoma were used for comparing demographic, clinical, pathological and survival data. RESULTS: The incidence of unclassified renal cell carcinoma was 2.9%. At initial diagnosis 29 patients (94%) with unclassified and 264 (83%) with clear cell renal cell carcinoma had metastatic disease (p = 0.143). Compared with the clear cell variety unclassified disease was associated with larger tumors (p = 0.005), increased risk of adrenal gland involvement (25% of cases, p = 0.0001), direct invasion to adjacent organs (42%, p = 0.00001), bone (52%, p = 0.022), regional (52%, p = 0.0042) and nonregional lymph node (41%, p = 0.03) metastases. Nephrectomy was less likely to be attempted or completed in unclassified renal cell carcinoma cases (61%, p = 0.00007). Unclassified histology was a significant indicator for poor prognosis on multivariate analysis (p <0.0001). Median survival in patients with unclassified renal cell carcinoma was 4.3 months. Nephrectomy alone did not confer any survival advantage in these cases (p = 0.1086), while immunotherapy did (p = 0.008). The combination of nephrectomy and immunotherapy yielded improved survival over immunotherapy alone (p = 0.0356) but patients with unclassified renal cell carcinoma were significantly less likely than those with clear cell disease to be eligible for immunotherapy regimens (p = 0.05). CONCLUSIONS: Unclassified renal cell carcinoma is associated with distinct and highly aggressive biological behavior, and poor clinical outcome. Whenever feasible, immunotherapy with nephrectomy is warranted.

Adult↗

Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate?

PURPOSE: We examined whether cytoreductive nephrectomy in patients with venous tumor thrombus and metastatic disease is associated with more complications than in those with thrombus without metastatic disease. MATERIALS AND METHODS: Between 1989 and 2000, 74 patients with renal vein extension, 87 with inferior vena caval extension and 491 without tumor thrombus underwent nephrectomy at our institution. Metastatic and nonmetastatic renal vein extension in 51 and 23 cases, inferior vena caval extension in 54 and 33, and nontumor thrombus in 171 and 320, respectively, were compared for symptoms at presentation, surgical data, mortality and complications. RESULTS: For nonmetastatic and metastatic inferior vena caval extension presenting symptoms, hospital stay, surgical time and the number of patients undergoing thoraco-abdominal incision, lymph node dissection, venacavotomy alone for thrombus and adrenal sparing surgery were similar. Five patients with thrombus died intraoperatively or postoperatively, including 3.1% with and 0.8% without thrombus (p = 0.03), while 3 had metastatic (2.3%) and 2 (2.6%) had nonmetastatic disease. The rate of postoperative complications was higher in thrombus cases overall but there was no difference in nonmetastatic and metastatic disease with thrombus. On multivariate analysis inferior vena caval thrombus (odds ratio 10.5), adjacent organ resection due to locally advanced tumor (odds ratio 6), partial nephrectomy (odds ratio 3.8), regional lymph node involvement (odds ratio 1.7) and lower preoperative hemoglobin (odds ratio 1.6) were independent variables predicting bleeding requiring transfusion. Inferior vena caval thrombus (odds ratio 1.7) and adjacent organ resection (odds ratio 2) were also associated with nonhemorrhagic complications. Systemic metastasis was not an independent risk factor in either analysis. CONCLUSIONS: To our knowledge there are no published data comparing surgical complications in patients with metastatic and nonmetastatic renal cell carcinoma who have gross tumor thrombus. Cytoreductive surgery in patients with thrombus and metastasis is not associated with an increase in the extent of surgery, morbidity or mortality compared with their counterparts with nonmetastatic disease.

Carcinoma, Renal Cell↗

CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography.

PURPOSE: We developed a prostate cancer tumor model capable of being noninvasively imaged using positron emission tomography (PET) based on expression of the herpes simplex virus thymidine kinase (HSV1-tk) reporter gene. MATERIALS AND METHODS: The androgen independent, metastatic prostate cancer cell lines CL1 and CL1-GFP were stably transfected with the mutant HSV1-tk gene pcDNA3.1/pCMV-sr39tk, which has increased ability to phosphorylate penciclovir. The presence of the sr39tk gene product was analyzed by Western blot analysis and relative thymidine kinase enzyme activity was assessed by a functional thymidine kinase enzyme activity assay. Subcutaneous and orthotopic CL1 and CL1-SR39 tumor xenografts were established in SCID mice. The ability to image CL1-SR39 was assessed using fluorodeoxyglucose and F-penciclovir ( F-FHBG) micro-PET (a rodent PET scanner). To investigate the systemic distribution of intratumoral sr39tk injections established CL1 tumors were transiently injected with first generation adenoviral vectors carrying the sr39tk gene under control of the strong cytomegalovirus promoter Ad-CMV-HSV1-sr39tk and imaged using micro-PET. RESULTS: Transfection of sr39tk into CL1 cells was successful. CL1-SR39 thymidine kinase enzyme activity was greater than twice the activity of the glioma cell line C6-SR39 control and above the threshold necessary for micro-PET detection. Fluorodeoxyglucose micro-PET in SCID mice was positive for CL1 and CL1-SR39 tumors. Selective micro-PET of subcutaneous CL1-SR39 tumors was done using F-FHBG. Micro-PET imaging after systemic and intratumoral injection of Ad-CMV-HSV1-sr39tk revealed significant systemic transgene leakage with significant hepatic expression of sr39TK protein. CONCLUSIONS: Molecular based imaging of sr39tk transfected prostate cancer tumors and adenoviral delivered HSV1-tk suicide gene therapy based on the selective conversion and intracellular trapping of F-FHBG by sr39tk is feasible. Potential applications include noninvasive monitoring of the location, duration and intensity of gene constructs, which may contribute to the safety of clinical gene therapy protocols, and noninvasive imaging of the prostate cancer xenograft response to experimental therapy.

Acyclovir↗

Collecting duct renal cell carcinoma: clinical study of a rare tumor.

PURPOSE: Collecting duct carcinoma is a rare type of renal cell carcinoma that affects younger patients, and is associated with aggressive regional and distant spread. The clinical and pathological features of 6 patients with collecting duct carcinoma treated at a single institution are described. MATERIALS AND METHODS: There were 6 patients with collecting duct carcinoma included in the University of California School of Medicine, Los Angeles, Kidney Cancer Database. Demographic, clinical, pathological and survival data were gathered. RESULTS: Average patient age plus or minus standard deviation was 56 +/- 11 years, and 5 of 6 had TNM stage IV disease. The average survival of these patients was 11.5 months (range 7 to 17). There was 1 patient who had TNM stage I disease and survived without evidence of disease at 5 years. Transient response to chemotherapy was seen in 1 patient. CONCLUSIONS: Collecting duct carcinoma is associated with poor prognosis. For the majority of patients surgical treatment will not result in a cure. Previously recommended chemotherapy and/or immunotherapy appears to have a limited role in treatment of this disease, and early detection may be the best method for prolonging patient survival.

Aged↗

Cryosurgical ablation of renal tumors using 1.5-millimeter, ultrathin cryoprobes.

INTRODUCTION: To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ultrathin cryoprobes. Renal cryosurgery is an evolving surgical technique, and uncertainties exist regarding the ideal approach to freezing renal tumors. TECHNICAL CONSIDERATIONS: Using an open surgical approach, a 3-cm upper pole renal mass was ablated using five, state-of-the-art, 1.5-mm cryoprobes simultaneously under real-time ultrasound guidance. The technique is described and demonstrated in a multisegment, Internet-based video tutorial. The blood loss was minimal, and no intraoperative or postoperative complications were experienced. Follow-up imaging at 3 months suggested shrunken, nonviable tumor. CONCLUSION: Cryosurgical ablation of renal tumors using multiple 1.5-mm cryoprobes is a safe, feasible approach that may be associated with a decreased risk of bleeding.

Adenocarcinoma, Clear Cell↗

[New trends in the diagnosis and treatment of renal cell carcinoma].

In the last decade the treatment of renal cell carcinoma (RCC) have changed dramatically. Currently, laparoscopic radical nephrectomy, partial nephrectomy in the presence of normal contralateral kidney as well as ablative surgery for small renal masses, are vivid options for the treatment of localized RCC. For metastatic RCC, cytoreductive nephrectomy is the standard of care prior to immunotherapy or combined treatment with tumor vaccines. On the horizon are: laparoscopic partial nephrectomy for localized disease and allogenic dendritic cell--autologous tumor cell hybrid vaccines as a non-toxic tumor vaccine. More experimental therapies involving targeting RCC cells using specific markers such as G250 are under investigation. In addition, changes in the 1997 TNM classification of RCC are anticipated. Retiring--routine adrenalectomy during radical nephrectomy and immunotherapy using tumor infiltrating lymphocytes (TIL).

Biomarkers, Tumor↗

Laparoscopic and percutaneous ablative techniques in the treatment of renal cell carcinoma.

Widespread use of computed tomography, ultrasound, and magnetic resonance imaging has led to an increase in detection of relatively small renal masses, and approaches to managing them have evolved in the last two decades. Indications for nephron-sparing surgery have expanded, and minimally invasive procedures, which can confer advantages over open surgery, are now available. Ablative techniques offer a combination of nephron-sparing and minimally invasive approaches. Ablative techniques include cryoablation, radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU). Cryoablation and RFA have been relatively safe. HIFU has been associated with serious side effects in animal models, and is not yet acceptable for use in humans. Ablative techniques require long-term studies to confirm lasting efficacy. The best modality for tumor targeting, monitoring of therapy, and follow-up is still under investigation. Debate exists regarding the best method for ensuring adequate intraoperative tumor cryoablation. For minimally invasive ablative measures to gain a place as nephron-sparing approaches, they should show both equivalent efficacy and reduced morbidity relative to those of open partial nephrectomy. These techniques should currently be reserved for selected patients and should be compared to the evolving modality of laparoscopic partial nephrectomy.

Journal Article↗

PSA elevation during prostate cryosurgery and subsequent decline.

PURPOSE: To determine the immediate effect of prostate cryosurgery on PSA and the subsequent decline. METHODS AND MATERIALS: PSA level was measured in 14 patients who underwent cryosurgery for prostate cancer. Blood samples were taken immediately before and after cryosurgery and 1, 2, 4, 6 weeks and 3 months postoperatively. A confidence interval for the elevation from baseline to maximal PSA was calculated. PSA decline was assessed in patients with a nadir PSA < or =0.5 ng/mL. Patients with a postoperative nadir PSA >0.5 ng/mL were considered to harbor viable cancer and were excluded from the decline analysis. The observed PSA levels during the postoperative period were compared with the expected levels that were calculated according to the maximal PSA level and a serum half-life of 2.5 days. Student t-test was used to compare expected and observed PSA levels. RESULTS: PSA increased from an average of 9.23 ng/mL preoperatively to a maximum average of 155 ng/mL (maximal PSA ranges: 18.9-490.5 ng/mL). The 95% CI for the increase in PSA from baseline level was 63.4 to 224.14. PSA nadir < or =0.5 ng/mL was achieved in 10 patients. The observed PSA decline course was slower than expected according to its half-life. Average observed and expected PSA levels at 2,4 and 6 weeks after cryosurgery were 10.4 versus 3.57 ng/mL (P = 0.005), 0.65 versus 0.07 (P = 0.007) and 0.09 versus 0.001 (P = 0.03), respectively. CONCLUSION: PSA levels increase steeply following cryosurgery, and decline slower than expected according to the serum half-life.

Adenocarcinoma↗

Cystic renal cell carcinoma: biology and clinical behavior.

The purpose of the study was to evaluate unilocular and multilocular cystic renal cell carcinoma (cRCC). These tumors are a rare entity, comprising approximately 1 to 2% of all renal tumors, and their true biologic behavior is not well-known. Initial review of renal cell carcinoma (RCC) cases treated at our institution between 1989 and 2001 identified 39 cases of cRCC. However, histopathologic review of these cases by 2 pathologists revealed that only 18 cases met the criteria that all tumors have a cystic component that constitutes at least 75% of the total lesion without evidence of necrosis. These cases were compared to 614 conventional clear cell RCC cases with regards to clinical outcomes. All 18 patients presented with localized (N0M0) disease. Thirteen (72%) of the tumors were Fuhrman Grade 1, while the remaining 5 (28%) were Fuhrman Grade 2. By comparison, only 60% of the clear cell RCC tumors were Grade 1 or 2. Similarly, 83% of cRCC were pT1 tumors compared to only 35% of conventional clear cell tumors. Mean tumor size for the cRCC tumors was 4.9 cm compared to 7.4 cm for conventional clear cell tumors. Cystic RCC patients had an 82% four-year disease-specific survival (DSS). Unilocular and multilocular cRCC is a distinct subtype of clear cell RCC. Its biology appears to be more favorable with regards to important prognostic factors such as metastatic presentation, Fuhrman grade, 1997 T stage, and tumor size. These findings suggest that cRCC patients may benefit from nephron sparing surgery.

Adult↗

A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma.

Cultured tumor lysate-loaded dendritic cells (TuLy-DC) have been demonstrated in vitro to stimulate potent immune modulations and generate significant antitumor response. We report the results of a pilot trial of TuLy-DC vaccine for patients with metastatic renal cell carcinoma (mRCC). Fourteen mRCC patients underwent nephrectomy to obtain autologous TuLy prepared by subjecting tumor cells to 3 freeze/thaw cycles. Dendritic cells were generated from peripheral blood CD14+ precursors cultured in the presence of GM-CSF, IL-4, and 10% autologous serum. Patients received one vaccination of TuLy alone as an immunologic control, followed by 3 weekly vaccinations of DC-TuLy injected intradermally in the midaxillary region. Peripheral blood lymphocytes were collected before and after weekly vaccines and were assessed for changes in phenotype, cytotoxicity, and cytokine profile. The TuLy-DC vaccine was successfully prepared and administered to 12 patients, whereas 2 patients did not receive vaccine treatment due to declines in postoperative performance status. The vaccines were well tolerated, with only grade 1 toxicities noted. One patient had a partial response to treatment that did not correspond to any significant change in immunologic profile. This pilot trial demonstrated both the safety and feasibility of reliably preparing a DC-based vaccine for mRCC patients. Our data suggest that autologous TuLy-DC vaccines generate only limited clinical response. Further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.

Adult↗