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Alla Turlakow - One of the best experts on this subject based on the ideXlab platform.
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Peritoneal Carcinomatosis: Role of 18F-FDG PET
2015Co-Authors: Alla Turlakow, Steven M LarsonAbstract:Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to eval-uate the role of 18F-FDG PET in detecting peritoneal carcinoma-tosis in patients with stomach, ovarian, and Adrenal Cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify charac-teristic patterns of abdominal 18F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. Methods: The medical records of 88 patients with stomach (n 48), ovarian (n 13), and Adrenal Cancer (n 6) and mesothelioma (n 21) were reviewed for the presence of peritoneal tumor on 18F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with sus-pected peritoneal tumor, 17 had biopsy-proven findings of peri-toneal disease. Results: Of the 24 patients with suspected peritoneal tumor, 18F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57 % (13/23), 42 % (10/23), and 78 % (18/23), with uniformly high positive predictive values of 93 % (13/14), 100 % (10/10), and 95 % (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform 18F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. Conclusion: 18F-FDG PET adds to conventional imaging in the staging of peritoneal car-cinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the pres-ence of either nodular or diffuse peritoneal pathology. Key Words: peritoneal carcinomatosis; 18F-FDG PET; scinti-graphic pattern
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peritoneal carcinomatosis role of 18f fdg pet
The Journal of Nuclear Medicine, 2003Co-Authors: Alla Turlakow, Henry W Yeung, Aida Sanchez Salmon, Homer A Macapinlac, Steven M LarsonAbstract:UNLABELLED: Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to evaluate the role of (18)F-FDG PET in detecting peritoneal carcinomatosis in patients with stomach, ovarian, and Adrenal Cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify characteristic patterns of abdominal (18)F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. METHODS: The medical records of 88 patients with stomach (n = 48), ovarian (n = 13), and Adrenal Cancer (n = 6) and mesothelioma (n = 21) were reviewed for the presence of peritoneal tumor on (18)F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with suspected peritoneal tumor, 17 had biopsy-proven findings of peritoneal disease. RESULTS: Of the 24 patients with suspected peritoneal tumor, (18)F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57% (13/23), 42% (10/23), and 78% (18/23), with uniformly high positive predictive values of 93% (13/14), 100% (10/10), and 95% (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform (18)F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. CONCLUSION: (18)F-FDG PET adds to conventional imaging in the staging of peritoneal carcinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the presence of either nodular or diffuse peritoneal pathology.
Steven M Larson - One of the best experts on this subject based on the ideXlab platform.
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Peritoneal Carcinomatosis: Role of 18F-FDG PET
2015Co-Authors: Alla Turlakow, Steven M LarsonAbstract:Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to eval-uate the role of 18F-FDG PET in detecting peritoneal carcinoma-tosis in patients with stomach, ovarian, and Adrenal Cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify charac-teristic patterns of abdominal 18F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. Methods: The medical records of 88 patients with stomach (n 48), ovarian (n 13), and Adrenal Cancer (n 6) and mesothelioma (n 21) were reviewed for the presence of peritoneal tumor on 18F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with sus-pected peritoneal tumor, 17 had biopsy-proven findings of peri-toneal disease. Results: Of the 24 patients with suspected peritoneal tumor, 18F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57 % (13/23), 42 % (10/23), and 78 % (18/23), with uniformly high positive predictive values of 93 % (13/14), 100 % (10/10), and 95 % (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform 18F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. Conclusion: 18F-FDG PET adds to conventional imaging in the staging of peritoneal car-cinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the pres-ence of either nodular or diffuse peritoneal pathology. Key Words: peritoneal carcinomatosis; 18F-FDG PET; scinti-graphic pattern
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peritoneal carcinomatosis role of 18f fdg pet
The Journal of Nuclear Medicine, 2003Co-Authors: Alla Turlakow, Henry W Yeung, Aida Sanchez Salmon, Homer A Macapinlac, Steven M LarsonAbstract:UNLABELLED: Peritoneal carcinomatosis can be difficult to diagnose, as CT is insensitive, with peritoneal biopsy and lavage often subject to problems of sampling error. The aim of our study was to evaluate the role of (18)F-FDG PET in detecting peritoneal carcinomatosis in patients with stomach, ovarian, and Adrenal Cancer and mesothelioma and to compare the results with CT scans in the same patient group. Our secondary aim was to identify characteristic patterns of abdominal (18)F-FDG uptake in biopsy-proven peritoneal disease and to correlate these patterns with available histologic and anatomic findings after surgery and structural imaging. METHODS: The medical records of 88 patients with stomach (n = 48), ovarian (n = 13), and Adrenal Cancer (n = 6) and mesothelioma (n = 21) were reviewed for the presence of peritoneal tumor on (18)F-FDG PET and CT scans. The results were correlated with either contemporaneous peritoneal biopsy or ascitic aspirate or with radiographic or clinical follow-up if histology was negative or unavailable. Of 24 patients with suspected peritoneal tumor, 17 had biopsy-proven findings of peritoneal disease. RESULTS: Of the 24 patients with suspected peritoneal tumor, (18)F-FDG PET was positive in 14 patients, with 1 of these scans being false-positive, CT was positive in 10 patients, and either PET or CT was positive in 18 patients. This yielded sensitivities of 57% (13/23), 42% (10/23), and 78% (18/23), with uniformly high positive predictive values of 93% (13/14), 100% (10/10), and 95% (18/19), respectively. We identified 2 distinctly abnormal scintigraphic patterns of focal and uniform (18)F-FDG uptake corresponding to nodular and diffuse peritoneal disease on pathologic examination. CONCLUSION: (18)F-FDG PET adds to conventional imaging in the staging of peritoneal carcinomatosis. It is also a useful diagnostic tool when peritoneal biopsy is either unavailable or inappropriate. We have identified 2 distinct scintigraphic patterns that appear to predict the presence of either nodular or diffuse peritoneal pathology.
Lidia Cerquetti - One of the best experts on this subject based on the ideXlab platform.
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antineoplastic effect of a combined mitotane treatment ionizing radiation in adrenocortical carcinoma a preclinical study
Cancers, 2019Co-Authors: Lidia Cerquetti, Barbara Bucci, G Carpinelli, Pina Lardo, Antonella Proietti, Raffaele Saporito, Guido Rindi, Elisa Petrangeli, Vincenzo Toscano, Antonio StiglianoAbstract:Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in Adrenal Cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, we used mouse xenografts bearing human ACC to test the effects of MTT and IR alone and in combination. We evaluated tumor growth inhibition by the RECIST criteria and analyzed the cell cycle by flow cytometry (FCM). In the xenograft ACC model treated with MTT/IR in combination, we observed a marked inhibition of tumor growth, with strong tumor regression (p < 0.0001) compared to MTT and IR given alone (p < 0.05). The MTT results confirm its antisteroidogenic activity (p < 0.05) in the xenograft ACC model, revealing its ability to render Cancer cells more prone to radiotherapy treatment. In addition, to explain the biological effect of these treatments on the Mismatch Repair System (MMR), we interfered with the MSH2 gene expression in untreated and MTT/IR-treated H295R and SW13 cell lines. Moreover, we observed that upon treatment with MTT/IR to induce DNA damage, MSH2 gene inhibition in both the H295R and SW13 cell lines did not allow DNA damage repair, thus inducing cell death. In conclusion, MTT seems to have a radiosensitizing property and, when given in combination with IR, is able to promote neoplastic growth inhibition, leading to a significant reduction in tumor size due to cell death.
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mitotane increases the radiotherapy inhibitory effect and induces g2 arrest in combined treatment on both h295r and sw13 adrenocortical cell lines
Endocrine-related Cancer, 2008Co-Authors: Lidia Cerquetti, Barbara Bucci, Rodolfo Marchese, Silvia Misiti, U De Paula, Roberto Miceli, A Muleti, Donatella Amendola, P Piergrossi, E BrunettiAbstract:Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD) is an agent with adrenotoxic effect, which is able to block cortisol synthesis. This drug and radiotherapy are used also in Adrenal Cancer treatment even if their biological action in this neoplasia remains unknown. We investigated the effects of o,p'-DDD and ionizing radiations (IR) on cell growth inhibition and cell cycle perturbation in H295R and SW13 adrenocortical Cancer cells. Both cell lines were irradiated at a 6 Gy dose and were treated with o,p'-DDD 10(-5) M separately and with IR/o,p'-DDD in combination. This combination treatment induced an irreversible inhibition of cell growth in both adrenocortical Cancer cells. Cell cycle analysis showed that IR alone and IR/o,p'-DDD in combination induced the cell accumulation in the G2 phase. At 120 h after IR, the cells were able to recover the IR-induced G2 block while cells treated with IR/o,p'-DDD were still arrested in G2 phase. In order to study the molecular mechanism involved in the G2 irreversible arrest, we have considered the H295R cell line showing the highest inhibition of cell proliferation associated with a noteworthy G2 arrest. In these cells, cyclin B1 and Cdk2 proteins were examined by western blot and Cdk2 kinase activity measured by assay kit. The H295R cells treated with IR/o,p'-DDD shared an increase in cyclin B1 amount as the coimmunoprecipitation of Cdc2-cyclin B1 complex. The kinase activity also shows an increase in the treated cells with combination therapy. Moreover, in these cells, sequence analysis of p53 revealed a large deletion of exons 8 and 9. The same irreversible block on G2 phase, induced by IR/o,p'-DDD treatment, happened in H295R cells with restored wild-type p53 suggesting that this mechanism is not mediated by p53 pathway.
Antonio Stigliano - One of the best experts on this subject based on the ideXlab platform.
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antineoplastic effect of a combined mitotane treatment ionizing radiation in adrenocortical carcinoma a preclinical study
Cancers, 2019Co-Authors: Lidia Cerquetti, Barbara Bucci, G Carpinelli, Pina Lardo, Antonella Proietti, Raffaele Saporito, Guido Rindi, Elisa Petrangeli, Vincenzo Toscano, Antonio StiglianoAbstract:Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in Adrenal Cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, we used mouse xenografts bearing human ACC to test the effects of MTT and IR alone and in combination. We evaluated tumor growth inhibition by the RECIST criteria and analyzed the cell cycle by flow cytometry (FCM). In the xenograft ACC model treated with MTT/IR in combination, we observed a marked inhibition of tumor growth, with strong tumor regression (p < 0.0001) compared to MTT and IR given alone (p < 0.05). The MTT results confirm its antisteroidogenic activity (p < 0.05) in the xenograft ACC model, revealing its ability to render Cancer cells more prone to radiotherapy treatment. In addition, to explain the biological effect of these treatments on the Mismatch Repair System (MMR), we interfered with the MSH2 gene expression in untreated and MTT/IR-treated H295R and SW13 cell lines. Moreover, we observed that upon treatment with MTT/IR to induce DNA damage, MSH2 gene inhibition in both the H295R and SW13 cell lines did not allow DNA damage repair, thus inducing cell death. In conclusion, MTT seems to have a radiosensitizing property and, when given in combination with IR, is able to promote neoplastic growth inhibition, leading to a significant reduction in tumor size due to cell death.
David E Schteingart - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for mitotane activity development of analogs for treatment of Adrenal Cancer
Anticancer Research, 2012Co-Authors: David E Schteingart, Joseph E Sinsheimer, Ricardo Benitez, Dominic Homan, Timothy D Johnson, Raymond E CounsellAbstract:Aim: Mitotane is used in Adrenal Cancer as adjuvant therapy, monotherapy or combined with other cytotoxic agents in advanced disease, but only 30% of patients respond. The aim of this study was to define the structural requirements for drug activity and to develop analogs with improved Adrenalytic action. Materials and Methods: Nine analogs of (1-(2-chlorophenyl)-1-(4- chlorophenyl)-2,2dichloroethane) (o,p'-DDD) were tested by measuring suppression of cortisol secretion and the presence of inflammatory changes in the dog Adrenal and inhibition of cell proliferation and cortisol production by NCI-H295 human Adrenal Cancer cells. Results: In addition to mitotane, o,p'-DDClBr and o,p'-DDBr 2 , were active in vitro and in vitro: Their effects were comparable to that of o,p'-DDD when tested at 50 μM concentration, but o,p'DDBr 2 was significantly more active at the lower 20 μM concentration. Conclusion: A dihalogenated methine carbon is required for Adrenalytic activity. A change in the aromatic portion of the mitotane molecule causes loss of activity. Because of its greater activity at lower concentrations, o,p'-DDBr 2 has potential application in the treatment of patients with Adrenal Cancer. Adrenal cortical carcinomas are rare, highly malignant tumors that account for only 0.2% of Cancer related deaths (1). Their incidence has been estimated at two per million people annually. About half of these tumors produce hormonal and metabolic syndromes that lead to their discovery. The other half is silent and is discovered when metastases develop or when the primary tumor becomes large enough to produce abdominal symptoms (1). Mitotane is an Adrenalytic drug that has been used for several decades in the treatment of patients with metastatic Adrenal cortical carcinoma (ACC), either as monotherapy or in combination with other chemotherapeutic drugs (2-10). Renewed interest in the drug has led to additional clinical
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adjuvant mitotane therapy of Adrenal Cancer use and controversy
The New England Journal of Medicine, 2007Co-Authors: David E SchteingartAbstract:Adrenocortical carcinoma is a rare, highly malignant neoplasm with an incidence of 2 cases per 1 million population per year worldwide, representing 0.2% of all cases of Cancer. Several treatment strategies in patients with advanced disease have resulted in temporary or partial tumor regression, yet very few patients attain long-term survival. Assessing the effectiveness of most published treatment protocols has been difficult, since most series have been limited by the inclusion of relatively few subjects, with tumors at various stages and grades. Several drug regimens have been used, and multiple treatments have been administered in various sequences. In addition, the . . .
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management of patients with Adrenal Cancer recommendations of an international consensus conference
Endocrine-related Cancer, 2005Co-Authors: David E Schteingart, Gary D Hammer, Gerard M Doherty, Paul G Gauger, Thomas J Giordano, Melvin Korobkin, F WordenAbstract:Adrenocortical carcinomas are rare, highly malignant tumors that account for only 0.2% of deaths due to Cancer. Given the limited number of patients seen in most medical centers with this diagnosis, series usually reported are small and clinical trials not randomized or blinded. In an attempt to answer important questions concerning the management of patients with Adrenal Cancer, a consensus conference was organized and held at the University of Michigan in Ann Arbor, MI, 11-13 September 2003, with the participation of an international group of physicians who had reported on the largest series of patients with this disease and who had recognized basic and clinical research expertise in Adrenal cortical Cancer. Totally 43 questions were addressed by the presenters and recommendations discussed in plenary and breakout sessions. Evidence for the recommendations of this conference was at the 2-4+ level and based on available literature and participants' experience. In addition to setting up guidelines in specific areas of the diagnosis and treatment of Adrenal Cancer, the conference recommended and initiated the planning of an international prospective trial for treatment of patients with Adrenal Cancer in stages III and IV. In terms of new therapies, first trials of dendritic cell therapy in human subjects with Adrenal Cancer have been started, but it is too early to comment on efficacy. Different strategies of immunotherapy, including DNA vaccination are currently being tried in animal models. There are no clinical gene therapy trials for human Adrenal cortical Cancer. The Adrenals are a preferred target for adenovirus and the results of gene therapy in preclinical studies are promising. In addition, there is evidence that histone deacetylase inhibitors can further enhance the rate of adenoviral infectivity in human Adrenal Cancer cells. Testing of retroviral vectors, non-viral vectors, small interfering RNA technology, and combined approaches could be performed in various laboratories. Anti-angiogenic substances have only been applied in preclinical studies. The use of these and other agents in the treatment of Adrenal Cancer should be hypothesis-driven and based on a thorough analysis of tumor biology.