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Biomedical subjects

Michael Morse

Publications and source records attributed to Michael Morse.

10 recordsLinked to original sources
PubMed2006

Radical nephrectomy with en bloc resection of liver, diaphragm, and lung for locally invasive sarcomatoid renal cell carcinoma.

Despite the widespread use of abdominal imaging, some patients with renal cell carcinoma still present with advanced disease. We report 1 case of locally invasive sarcomatoid renal cell carcinoma requiring resection of the kidney, adrenal glands, liver, diaphragm, and lung, with diaphragmatic reconstruction with a polytetrafluoroethylene patch. The patient was alive and well 5 years postoperatively. However, we acknowledge that the success experienced with this case does not represent the typical outcome for a patient with such advanced disease.

Adult↗
PubMed2005

Technology evaluation: Rexin-G, Epeius Biotechnologies.

Rexin-G is a 'pathotropic', tumor-targeted, injectable retroviral vector carrying a mutant form of the cyclin G1 gene, under development by Epeius Biotechnologies for the potential treatment of metastatic cancer. The therapy is currently undergoing phase I/II clinical trials.

Animals↗
PubMed2003

Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA.

BACKGROUND: Studies have suggested an increased risk of peritoneal seeding in patients with pancreatic cancer diagnosed by percutaneous FNA. EUS-FNA is an alternate method of diagnosis. The aim of this study was to compare the frequency of peritoneal carcinomatosis as a treatment failure pattern in patients with pancreatic cancer diagnosed by EUS-FNA vs. percutaneous FNA. METHODS: Retrospective review of patients with non-metastatic pancreatic cancer identified 46 patients in whom the diagnosis was made by EUS-FNA and 43 with the diagnosis established by percutaneous FNA. All had neoadjuvant chemoradiation. Patients underwent restaging CT after completion of therapy, followed by attempted surgical resection if there was no evidence of disease progression. RESULTS: There were no significant differences in tumor characteristics between the two study groups. In the EUS-FNA group, one patient had developed peritoneal carcinomatosis compared with 7 in the percutaneous FNA group (2.2% vs. 16.3%; p<0.025). No patient with a potentially resectable tumor in the EUS-FNA group had developed peritoneal carcinomatosis. CONCLUSIONS: Peritoneal carcinomatosis may occur more frequently in patients who undergo percutaneous FNA compared with those who have EUS-FNA for the diagnosis of pancreatic cancer. A concern for peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS-guided FNA is recommended as the method of choice for diagnosis in patients with potentially resectable pancreatic cancer.

Adult↗
PubMed2003

De-novo cholangiocarcinoma in the setting of recurrent primary sclerosing cholangitis following liver transplant.

Orthotopic liver transplantation is the only definitive therapeutic option in patients with primary sclerosing cholangitis (PSC) and end-stage liver disease. However, PSC recurs in up to 20% of patients transplanted for this indication. To date, no patient has been reported to develop cholangiocarcinoma (CCA) post-transplant, without biliary tract cancer having been present pretransplant. Here, we report recurrent PSC complicated by de-novo CCA in a 31-year-old man transplanted for PSC 8 years earlier. Cholangiocarcinoma was confirmed using a combination of computed tomography, cholangiography, positron emission tomography and histological examination of biliary cytology. He has since been successfully re-transplanted following preoperative chemo-radiotherapy. No viable tumor was identified in the explanted liver. This case establishes that long-term complications associated with PSC and biliary-enteric surgery such as CCA may become apparent in new grafts post-transplant.

Adult↗
PubMed2003

Adjuvant hepatic arterial chemotherapy following metastasectomy in patients with isolated liver metastases.

OBJECTIVE: To examine survival and toxicity by querying a single-institutional experience with adjuvant hepatic arterial infusional (HAI) chemotherapy. SUMMARY BACKGROUND DATA: Three randomized series in the literature have examined adjuvant HAI after complete resection of liver metastases. Only one of these trials showed an overall survival benefit at 2 years but not over the entire time period of the study. Previous studies in patients with unresectable disease were plagued by high rates of biliary toxicity. METHODS: A retrospective review of a prospectively maintained database was performed. Hepatic arterial pumps were placed in the standard fashion. Patients received floxuridine at doses previously demonstrated as safe in the literature. Standard statistical methods were used. RESULTS: Twenty-one of 92 patients underwent placement of hepatic arterial pumps at the time of liver resection. The HAI group was similar in all demographic measures to the non-HAI group, with the exception that the HAI patients were significantly younger. No differences were seen between the groups in either disease-free or overall survival, although a trend toward improved hepatic progression-free survival was noted. Significant biliary sclerosis developed in six patients in the HAI group, requiring chronic indwelling stents in four patients. One patient died of progressive liver failure associated with this toxicity. CONCLUSIONS: Biliary toxicity is an important potential side effect of hepatic arterial chemotherapy. Although larger randomized studies and this one suggest significant improvements in hepatic recurrences, these have not reliably translated into overall survival benefit. This fact, in light of the potential toxicity, would argue for a larger confirmatory trial of HAI in the adjuvant setting, incorporating recent advances in systemic therapy and careful attention to hepatotoxicity.

Adult↗
PubMed2002

Mobilization of dendritic cells from patients with breast cancer into peripheral blood stem cell leukapheresis samples using Flt-3-Ligand and G-CSF or GM-CSF.

Treatment with myeloablative chemotherapy and autologous peripheral blood stem cell (PBSC) transplantation followed by vaccination with autologous dendritic cells (DCs) treated with tumor antigens is a promising therapeutic strategy for several types of cancer. Obtaining sufficient numbers of both PBSCs and DCs is central to this approach. Previously, it has been shown that administration of Flt-3-Ligand (FL) combined with either G-CSF or GM-CSF mobilizes large numbers of PBSCs in patients with cancer. In the current study, we sought to determine whether these same cytokines could simultaneously mobilize DCs into the PBSC leukapheresis collection. DCs were analysed in PBSC leukapheresis samples obtained from five patients with high-risk breast cancer who received G-CSF alone as priming prior to leukapheresis, four patients who received FL+G-CSF and five patients who received FL+GM-CSF. DCs were defined as cells with a lin(dim/-) HLA-DR+ CD11c+ phenotype. The proportions of DCs in the FL+G-CSF and FL+GM-CSF samples were significantly higher than in pre-mobilization peripheral blood and G-CSF leukapheresis samples. The mean yield of DCs/kg in the FL+GM-CSF samples was also significantly higher than the mean yield of DCs in the G-CSF samples. The FL+G-CSF and FL+GM-CSF mobilized DCs were immature by morphologic and phenotypic criteria but stimulated allogeneic T-cells at levels similar to DCs generated in culture from PBMCs. Overnight culture?of the immature DCs obtained from patients receiving either FL+G-CSF or FL+GM-CSF in TNF-alpha?resulted in the generation of mature DCs. In summary, administration of FL in combination with GM-CSF and G-CSF to patients with breast cancer can mobilize large numbers of immature DCs into PBSC leukapheresis collections.

Antibodies, Monoclonal↗
PubMed2002

Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy.

BACKGROUND: Although resection is the sole chance of cure in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer to the liver, most patients are not candidates for surgery at the time of diagnosis. Strategies aiming at downstaging large or multifocal tumors to enable curative resection are appealing. The aim of this study was to evaluate the effects of neoadjuvant selective intra-arterial chemotherapy in noncirrhotic patients with unresectable HCC or metastatic colorectal cancer to the liver in the absence of extrahepatic disease. METHODS: Selective chemotherapy was provided by using a subcutaneous pump device via a catheter placed in the gastroduodenal artery. Chemotherapy regimen included floxuridine (0.2 mg/kg/day for 14 days) in each patient with additional boluses of cisplatin and doxorubicin on day 1 of each cycle in the presence of HCC. Patients were evaluated at 3, 6, 9, and 12 months for possible curative resection. Complete follow-up was available for each patient. RESULTS: Twenty-eight patients with unresectable liver tumors (5 HCC and 23 metastatic colorectal cancer) were included in this study. There were no surgical complications related to pump insertion, and local chemotherapy was started within 1 week of surgery in each patient. The median follow-up in survivors was 31 months (range, 30 months to 5 years). Chemotherapy was well tolerated in 18 (64%) patients. Chemotherapy was discontinued in 4 patients because of abnormal liver function test results, and 2 of them required a biliary stent to relieve a biliary stricture. In 9 patients downstaging enabled curative resection (3 HCC, 6 colorectal metastasis). Seven of these patients were alive and tumor free at the completion of the study, with at least 2 years of follow-up. The actuarial survival rates at 3 years for HCC and colorectal metastases were 60% and 50%, respectively. CONCLUSIONS: About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.

Adult↗
PubMed2002

Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells.

OBJECTIVE: To demonstrate the feasibility of inducing tumor antigen-specific immune responses in patients with metastatic cancer using total tumor RNA-loaded dendritic cells (DCs). SUMMARY BACKGROUND DATA: The authors have shown that DCs transfected with mRNA encoding defined tumor antigens induce tumor antigen-specific T-cell responses in vitro and in vivo. There may be significant advantages to inducing immune responses against the entire repertoire of antigens expressed by a patient's autologous tumor. METHODS: RNA was extracted from a metastatic colon cancer and used to load autologous DCs. The DCs were coincubated with autologous T cells and the cytolytic activity of the T cells was assessed by the ability to lyse the autologous tumor cells. RNA was then extracted from a metastatic lung cancer and used to load autologous DCs, followed by four injections of the DC vaccine given every 4 weeks. Tumor antigen-specific cytotoxic T lymphocyte activity was then evaluated by testing peripheral blood mononuclear cells for their ability to lyse an antigen-expressing target. RESULTS: DCs transfected with the total RNA content of autologous tumor cells stimulated antigen-specific T-cell responses that are capable of recognizing and lysing autologous, primary tumor cells in vitro. Tumor-specific immune responses were induced in a patient with a carcinoembryonic antigen-expressing adenocarcinoma after immunization with autologous DCs transfected with total tumor RNA. CONCLUSIONS: DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of tumor antigens of surgically resected malignancies.

Adenocarcinoma↗
PubMed2002

Redirecting cytotoxic T lymphocyte responses with T-cell receptor transgenes.

In cancer and viral diseases, a great deal of research has focused on generating T-cell responses that might prove therapeutic. These efforts stem from our understanding of the immune system. It is known that the natural immune response can protect or suppress some viral infections and it is hoped that a potent T-cell mediated immune response might also be harnessed to fight cancer. Immunotherapy is a particularly attractive candidate therapy for the treatment of metastatic cancer because of the immune systems capacity for body wide surveillance. Since the generation of T cell clones is a laborious task and it is often impossible to derive T cell clones of the desired specificity and function from many individuals, especially in a timely fashion required for therapeutic interventions, T-cell receptor (TCR) gene transfer has a lot of appeal. TCR gene transfer seeks to transfer the antigen specificity of a T cell clone to other T cells. This article will review the last 15 years of research in TCR gene transfer since the first successful TCR gene transfer experiment, and seeks to give an insight into the areas of investigation currently being pursued to improve on current results and move TCR gene transfer into the clinic.

Animals↗