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2.
Open Biomed Eng J ; 4: 39-46, 2010 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-20309395

RESUMO

Liver resection is the current standard treatment for patients with both primary and metastatic liver cancer. The principal causes of morbidity and mortality after liver resection are related to blood loss (typically between 0.5 and 1 L), especially in cases where transfusion is required. Blood transfusions have been correlated with decreased long-term survival, increased risk of perioperative mortality and complications. The goal of this study was to evaluate different designs of a radiofrequency (RF) electrode array for use during liver resection. The purpose of this electrode array is to coagulate a slice of tissue including large vessels before resecting along that plane, thereby significantly reducing blood loss. Finite Element Method models were created to evaluate monopolar and bipolar power application, needle and blade shaped electrodes, as well as different electrode distances. Electric current density, temperature distribution, and coagulation zone sizes were measured. The best performance was achieved with a design of blade shaped electrodes (5 x 0.1 mm cross section) spaced 1.5 cm apart. The electrodes have power applied in bipolar mode to two adjacent electrodes, then switched sequentially in short intervals between electrode pairs to rapidly heat the tissue slice. This device produces a ~1.5 cm wide coagulation zone, with temperatures over 97 masculineC throughout the tissue slice within 3 min, and may facilitate coagulation of large vessels.

3.
Med Eng Phys ; 30(4): 454-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17588799

RESUMO

Hepatic resection is currently the standard treatment for liver cancer. During hepatic resection part of the liver containing the tumor is surgically removed. This type of surgery is accompanied by high blood loss of approximately 0.6-1.35 L. Blood loss is associated with increased complication rates, prolonged hospital stay, and reduced patient survival, especially when transfusion is required. Other researchers have suggested using radiofrequency (rf) or microwave ablation to coagulate a tissue slice before resection to reduce blood loss, but conventional devices typically take several hours. We developed a device consisting of a linear array of blade-shaped, 1 cm wide radiofrequency (rf) electrodes 1.5 cm apart. Bipolar rf power is applied between pairs of adjacent electrodes, leading to high tissue temperatures between the electrodes that promote coagulation of large vessels (>3 mm) in the resection plane. Rapid switching of applied power between pairs of adjacent electrodes allows simultaneous heating and coagulation of the entire resection plane within 3-6 min. In seven in vivo trials in a porcine model, resection along a plane pre-coagulated with the device resulted in little (<20 mL) to no blood loss, while coagulating all vessels (up to 4.5 mm diameter in this study). Average treatment time (from placement of the device to transection) was 6.8+/-0.5 min when four electrodes were used, and 11.3+/-1.2 min when 5-7 electrodes were used. This device may reduce blood loss related morbidity during resection and reduce treatment time by coagulating all vessels in the resection plane.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Fígado/efeitos da radiação , Fígado/cirurgia , Animais , Coagulação Sanguínea , Impedância Elétrica , Eletrodos , Desenho de Equipamento , Hemostasia Cirúrgica , Hepatectomia/métodos , Fígado/patologia , Ondas de Rádio , Procedimentos Cirúrgicos Operatórios/métodos , Suínos , Fatores de Tempo
4.
Ann Surg Oncol ; 14(10): 2953-60, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17674109

RESUMO

BACKGROUND: Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control. METHODS: Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local recurrence rates between groups. RESULTS: 290 subjects with an average age of 57.2 years (range 27-89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy. At a median follow-up of 53.4 months (range 5.8-137.8), there were six local recurrences (2.74%) in patients who had breast-conserving procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS compared with invasive carcinoma, and tumors >2cm. CONCLUSIONS: Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin assessment techniques.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mama/patologia , Secções Congeladas , Mastectomia Segmentar , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , Período Intraoperatório , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Reoperação , Estudos Retrospectivos
5.
Cancer Gene Ther ; 14(8): 717-23, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17557109

RESUMO

Effective eradication of established tumor and generation of a lasting systemic immune response are the goals of cancer immunotherapy. The objective of this phase IB study was to assess the safety and toxicity of treatment to metastatic tumor underlying the skin with the DNA encoding interleukin-12 (IL-12). This treatment strategy allowed the patient's own tumor to serve as a source of autologous antigen in the tumor microenvironment. We proposed that IL-12 protein produced by the transfected cells would result in the generation of both a local and systemic antitumor response. The tumor was treated with either three or six intratumoral injections of plasmid containing IL-12 DNA. This treatment strategy resulted in no significant local or systemic toxicity. The treatment did not result in an increase in serum IL-12 protein. The size of the treated lesion decreased significantly (greater than 30%) in five of the 12 patients. However, nontreated subcutaneous lesions or other disease did not decrease in size.


Assuntos
DNA de Neoplasias/administração & dosagem , Vetores Genéticos/administração & dosagem , Interleucina-12/administração & dosagem , Interleucina-12/genética , Melanoma/terapia , Plasmídeos/genética , Adulto , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , DNA de Neoplasias/efeitos adversos , Feminino , Vetores Genéticos/efeitos adversos , Humanos , Injeções Intralesionais , Interleucina-12/efeitos adversos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Masculino , Melanoma/genética , Melanoma/secundário , Pessoa de Meia-Idade
6.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 2503-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17270781

RESUMO

Hepatic resection is the current standard treatment for hepatic malignancies. During hepatic resection part of the liver containing the tumor is surgically removed. This type of surgery is associated with high blood loss of approximately 1 L. Blood loss is associated with increased complication rates, prolonged hospital stay and reduced patient survival, especially when transfusion is required. We present a device that allows coagulation of a plane of tissue 1 to 2 cm wide, including coagulation of large vessels. This enables reduction of blood loss to a minimum by performing surgery along the coagulated tissue plane. The device consists of a linear array of radiofrequency (RF) electrodes 1.5 cm apart. By application of RF current in bipolar mode between two adjacent electrodes, temperatures close to 100 degrees C are obtained in-between electrodes enabling coagulation of large vessels. Rapid switching of applied current between all adjacent electrode pairs enables rapid heating of a tissue slice. We present a prototype device including results from ex vivo and in vivo experiments.

7.
Med Biol Eng Comput ; 41(3): 317-23, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12803297

RESUMO

Radiofrequency (RF) ablation has become an important means of treatment of non-resectable primary and metastatic liver tumours. Recurrence of treated tumours is associated with cancer cell survival next to blood vessels. The paper examines the performance of classical monopolar, and two configurations of bipolar, RF ablation using a LeVeen ten-prong catheter. Finite element method models of monopolar and bipolar configurations were created at 5 mm distance from a vessel of the size of a typical portal vein (10 mm diameter). In one bipolar configuration, the probes were oriented in the same axial direction (asymmetric configuration); in the second bipolar configuration, the two probes were facing each other (symmetric configuration). The distribution of temperature and current density was analysed for three different flow conditions: normal flow, reduced flow due to portal hypertension and high flow. For normal flow, the distance between the formed coagulation zone and the blood vessel was 1.8 mm for monopolar, 1 mm for asymmetric bipolar, and 0.2 mm for symmetric bipolar, configurations. Symmetric bipolar RF ablation creates coagulation zones significantly closer to blood vessels compared with monopolar RF ablation. This may reduce tumour cell survival next to blood vessels and reduce recurrence rates.


Assuntos
Ablação por Cateter/métodos , Análise de Elementos Finitos , Neoplasias Hepáticas/cirurgia , Modelos Biológicos , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Temperatura
8.
Physiol Meas ; 24(2): 251-60, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12812412

RESUMO

Knowledge of electrical tissue conductivity is necessary to determine deposition of electromagnetic energy and can further be used to diagnostically differentiate between normal and neoplastic tissue. We measured 17 rats with a total of 24 tumours of the K12/TRb rat colon cancer cell line. In each animal we measured in vivo hepatic tumour and normal tissue conductivity at seven frequencies from 10 Hz to 1 MHz, at different tumour stages between 6 and 12 weeks after induction. Conductivity of normal liver tissue was 1.26 +/- 0.15 mS cm(-1) at 10 Hz, and 4.61 +/- 0.42 mS cm(-1) at 1 MHz. Conductivity of tumour was 2.69 +/- 0.91 mS cm(-1) at 10 Hz, and 5.23 +/- 0.82 mS cm(-1) at 1 MHz. Conductivity was significantly different between normal and tumour tissue (p < 0.05). We determined the percentage of necrosis and fibrosis at the measurement site. We fitted the conductivity data to the Cole-Cole model. For the tumour data we determined Spearman's correlation coefficients between the Cole-Cole parameters and age, necrosis, fibrosis and tumour volume and found significant correlation between necrosis and the Cole-Cole parameters (p < 0.05). We conclude that necrosis within the tumour and the associated membrane breakdown is likely responsible for the observed change in conductivity.


Assuntos
Neoplasias do Colo , Condutividade Elétrica , Neoplasias Hepáticas/diagnóstico , Animais , Linhagem Celular Tumoral , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Modelos Biológicos , Necrose , Transplante de Neoplasias , Ondas de Rádio , Ratos , Ratos Endogâmicos BN , Som
9.
Hum Gene Ther ; 13(14): 1711-21, 2002 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-12396624

RESUMO

The primary objective of this phase I study was to determine the safety of an autologous tumor vaccine given by intradermal injection of lethally irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected autologous melanoma and sarcoma cells. Secondary objectives included validation of the gene delivery technology (particle-mediated gene transfer), determining the host immune response to the tumor after vaccination, and monitoring patients for evidence of antitumor response. Sixteen patients were treated with either of two different doses of GM-CSF-treated tumor cells. One patient received treatment with both doses of tumor cells. No treatment-related local or systemic toxicity was noted in any patient. Patients administered 100% treated cells (i.e., with a preparation of tumor cells that had all been exposed to GM-CSF DNA transfection) had a more extensive lymphocytic infiltrate at the vaccine site than did patients given 10% treated cells (a preparation of tumor cells in which 10% had been exposed to GM-CSF transfection) or nontreated tumor. The generation of a systemic immune response to autologous tumor by a delayed-type hypersensitivity response to the intradermal placement of nontransfected tumor cells was noted in one patient. One patient had a transient partial response of metastatic tumor sites. The entire procedure, from tumor removal to vaccine placement, was accomplished in less than 6 hr in all patients. Four of 17 patient tumor preparations produced greater than 3.0 ng of GM-CSF per 10(6) cells per 24 hr in vitro. The one patient with greater than 30 ng of GM-CSF per 10(6) cells per 24 hr in vitro had positive DTH, a significant histologic inflammatory response, and clinically stable disease. This technique of gene transfer was safe and feasible, but resulted in clinically relevant levels of gene expression in only a minority of patients.


Assuntos
Biolística , Vacinas Anticâncer/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fatores Imunológicos/genética , Melanoma/terapia , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Vacinas de DNA/uso terapêutico , Vacinas Anticâncer/administração & dosagem , DNA Complementar/genética , Relação Dose-Resposta Imunológica , Estudos de Viabilidade , Ouro , Humanos , Hipersensibilidade Tardia/imunologia , Injeções Intradérmicas , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Lipossarcoma/patologia , Lipossarcoma/terapia , Melanoma/patologia , Melanoma/secundário , Segurança , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento , Células Tumorais Cultivadas/transplante , Vacinas de DNA/administração & dosagem
10.
Med Biol Eng Comput ; 40(1): 29-33, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11954705

RESUMO

The resistivity of swine liver tissue was measured in vivo, during induced ischaemia and post-mortem, so that associated changes in resistivity could be quantified. Plunge electrodes, the four-terminal method and a computer-automated measurement system were used to acquire resistivities between 10Hz and 1 MHz. Liver resistivity was measured in vivo in three animals at 11 locations. At 10 Hz, resistivity was 758 +/- 170 ohm x cm. At 1 MHz, the resistivity was 250 +/- 40 ohm x cm. The resistivity time course was measured during the first 10 min after the liver blood supply in one animal had been occluded. Resistivity increased steadily during occlusion. The change in resistivity of an excised tissue sample was measured during the first 12h after excision in one animal. Resistivity increased during the first 2h by 53% at 10 Hz and by 32% at 1 MHz. After 2h, resistivity decreased, probably owing to membrane breakdown. The resistivity data were fitted to a Cole-Cole circle, from which extracellular resistance Re, intracellular resistance Ri and cell membrane capacitance Cm were estimated. Re increased during the first 2h by 95% and then decreased, suggesting an increase in extracellular volume. Cm increased during the first 4 h by 40%, possibly owing to closure of membrane channels, and then decreased, suggesting membrane breakdown. Ri stayed constant during the initial 6h and then increased.


Assuntos
Isquemia/fisiopatologia , Fígado/fisiopatologia , Suínos/fisiologia , Animais , Impedância Elétrica , Fígado/irrigação sanguínea , Potenciais da Membrana
11.
IEEE Trans Biomed Eng ; 48(10): 1145-52, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11585038

RESUMO

Radio-frequency (RF) ablation has become an important means of treatment of nonresectable primary and metastatic liver tumors. Major limitations are small lesion size, which make multiple applications necessary, and incomplete killing of tumor cells, resulting in high recurrence rates. We examined a new bipolar RF ablation method incorporating two probes with hooked electrodes (RITA model 30). We performed monopolar and bipolar in vivo experiments on three pigs. The electrodes were 2.5 cm apart and rotated 45 degrees relative to each other. We used temperature-controlled mode at 95 degrees C. Lesion volumes were 3.9+/-1.8 cm3 (n=7) for the monopolar case and 12.2 +/- 3 cm3 (n=10) for the bipolar case. We generated finite-element models (FEMs) of monopolar and bipolar configurations. We analyzed the distribution of temperature and electric field of the finite element model. The lesion volumes for the FEM are 7.95 cm3 for the monopolar and 18.79 cm3 for the bipolar case. The new bipolar method creates larger lesions and is less dependent on local inhomogenities in liver tissue-such as blood perfusion-compared with monopolar RF ablation. A limitation of the new method is that the power dissipation of the two probes cannot be controlled independently in response to different conditions in the vicinity of each probe. This may result in nonuniform lesions and decreased lesion size.


Assuntos
Ablação por Cateter/instrumentação , Fígado/cirurgia , Animais , Eletrodos , Análise de Elementos Finitos , Neoplasias Hepáticas/cirurgia , Suínos
12.
Cancer ; 92(5): 1288-98, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11571745

RESUMO

BACKGROUND: Studies that prospectively and simultaneously evaluate, within the first year of diagnosis, the impact of surgery and chemotherapy on quality of life (QOL) of younger women (60 years or younger) with early stage breast carcinoma are limited. METHODS: Quality of life of 103 women who had surgery (lumpectomy, 49; mastectomy, 54) approximately 1 month before the start of the study was evaluated at baseline and again after 5 months. Thirty-two women received chemotherapy during the study. RESULTS: Over time, subjects reported improvement in body image and physical, emotional, and functional well-being (P < 0.001). They were less bothered by swollen/tender arms and worried less about risk of cancer to family members (P < 0.001). However, satisfaction with sex life, social support, and social/family well-being declined (P < 0.001). In the period closer to surgery, women with mastectomy reported poorer body image (P = 0.001) and worse functional (P = 0.08) and physical well-being (P = 0.10). Women with lumpectomy worried more about the effects of stress on their illness (P < 0.01) and had lower emotional well-being (P = 0.06). By 6 months after surgery, the two groups reported similar QOL scores. Chemotherapy had a negative impact on women's sexual functioning (P = 0.01) and their physical well-being (P = 0.09). Women who received chemotherapy also reported more shortness of breath (P = 0.07). Post hoc analysis showed that women with breast reconstruction had higher emotional well-being at baseline than those with lumpectomy (P = 0.001) and mastectomy alone (P < 0.01). CONCLUSIONS: Younger women with breast carcinoma could experience a range of adjustment problems at various points in the treatment cycle. Interventions that would help reduce the negative impact of treatment on QOL need to be designed and integrated into routine clinical practice.


Assuntos
Adaptação Psicológica , Neoplasias da Mama , Qualidade de Vida , Adulto , Antineoplásicos/uso terapêutico , Imagem Corporal , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia/psicologia , Mastectomia Segmentar/psicologia , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos
13.
J Gastrointest Surg ; 5(2): 206-13, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11331484

RESUMO

Only 5% to 10% of metastatic and primary liver tumors are amenable to surgical resection. Hepatic cryoablation has increased the number of patients who are suitable for curative treatment. The aim of this study was to evaluate survival and intrahepatic recurrence in patients treated with cryoablation and resection. From June 1994 to July 1999, thirty-eight surgically unresectable patients underwent a total of 42 cryoablative procedures for 65 malignant hepatic lesions. Twenty patients underwent cryoablation alone, and 18 patients were treated with a combination of resection and cryoablation, with a minimum of 18 months' follow-up. The 38 patients had the following malignancies: primary hepatocellular carcinoma (n = 8) and metastases from colorectal cancer (n = 21), neuroendocrine tumors (n = 3), ovarian cancer (n = 3), leiomyosarcoma (n = 1), testicular cancer (n = 1), and endometrial cancer (n = 1). Patients were evaluated preoperatively with spiral CT scans and intraoperatively with ultrasound examinations for lesion location and cryoprobe guidance. Local recurrence was detected by CT. Major complications included bleeding in three patients and acute renal failure, transient liver insufficiency, and postoperative pneumonia in one patient each. Two patients (5%) died during the early postoperative interval; mean hospital stay was 7.1 days. Median follow-up was 28 months (range 18 to 51 months). Overall survival according to Kaplan-Meier analysis was 82%, 65%, and 54% at 12, 24, and 48 months, respectively. Forty-eight-month survival was not significantly different between those patients undergoing cryoablation alone (64%) and those treated with a combination of resection and cryoablation (42%). Disease-free survival at 45 months was 36% for patients undergoing cryoablation plus resection compared to 25% for those undergoing cryoablation alone. Local recurrences were detected at five cryosurgical sites, for a rate of 12% overall (5 of 42), 11% (2 of 18) for patients in the cryoablation plus resection group, and 12% (3 of 24) for those in the cryoablation alone group. For patients with colorectal metastases, survival was 70% at 30 months compared to 33% for hepatocellular cancer and 66% for other types of tumors. Patients with tumors larger than 5 cm or numbering more than three did not have significantly decreased survival. Cryoablation of hepatic tumors is a safe and effective treatment for some patients not amenable to resection. The combination of cryoablation and resection results in survival comparable to that achieved with cryoablation alone.


Assuntos
Criocirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Contraindicações , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
14.
J Vasc Surg ; 33(4): 806-11, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11296336

RESUMO

PURPOSE: Aneurysms of the visceral arteries are infrequently encountered. Many are found incidentally and are thought to have a benign outcome. To better characterize these lesions and their clinical course, we reviewed our experience with visceral artery aneurysms (VAAs) at a single institution. METHODS: A retrospective analysis of all VAAs diagnosed at our institution over the past 10 years was performed. The presentation, management, and outcome of therapy was examined for each patient. RESULTS: Thirty-four VAAs in 26 patients were diagnosed over the past 10 years. Four patients had multiple VAAs: splenic (17), hepatic (7), celiac (3), superior mesenteric (2), gastroduodenal (2), pancreaticoduodenal (1), right gastric (1), ileal (1) artery aneurysms. Associated aneurysms were found in 31% of patients and involved the thoracic aorta (3 patients), abdominal aorta (4 patients), renal arteries (2 patients), iliac artery (3 patients), lower extremity (1 patient), and intracranium (1 patient). In 15 patients (58%), VAAs were detected before rupture by chance or because abdominal symptoms resulted in diagnostic evaluation. Eight of these underwent elective surgery, and there were no deaths. Of those 15 patients with known VAAs, one patient died of rupture and hemorrhage from an untreated splenic artery aneurysm. Eleven patients (42%) presented unexpectedly with rupture, and two died despite prompt surgical treatment. The mortality rate in patients who had ruptured VAAs was 25%, including those who presented with ruptured aneurysms and those observed whose aneurysms eventually ruptured. CONCLUSIONS: Aneurysms of the visceral arteries are rare but important vascular lesions. Associated aneurysms are common. Because of the risk of rupture, often with a fatal outcome, an aggressive approach to the treatment of VAA is essential.


Assuntos
Aneurisma Roto/cirurgia , Vísceras/irrigação sanguínea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico , Aneurisma Roto/mortalidade , Angiografia Digital , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
15.
Cancer Gene Ther ; 8(2): 118-27, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11263527

RESUMO

IL-12 gene therapy results in tumor regression in some, but not all, murine models. We hypothesized that expression of B7.1 on the tumor cell surface was necessary for IL-12-mediated tumor regression. In addition, we hypothesized that all cells must express B7.1 for this to be effective. To evaluate this hypothesis, tumor nodules were established in mice with either wild-type B16 melanoma or with B16 melanoma modified to express B7.1. IL-12 cDNA was transferred to the tumor by particle-mediated gene transfer. All tumors modified to express B7.1 regressed completely after IL-12 cDNA treatment. When the percent of B7.1-transfected B16 cells was decreased to 50%, no animals survived after treatment. Animals rendered tumor-free were then challenged with wild-type B16. Fifty percent of mice was protected from this tumor challenge. Expression of CD28 (the stimulatory B7.1 ligand) was significantly increased in both CD8(+) T cells and natural killer cell populations of mice rejecting tumor challenge compared to mice with tumor growth. These results suggest that the costimulatory molecule B7.1 is required for initial tumor sensitivity to IL-12 gene therapy and that protection from subsequent challenge with B7.1 (-) tumor is mediated by CD28(+) immune effector cells.


Assuntos
Antígeno B7-1/metabolismo , Terapia Genética , Imunoconjugados , Interleucina-12/genética , Melanoma Experimental/terapia , Abatacepte , Animais , Antígenos CD , Antígenos de Diferenciação/metabolismo , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antígeno CTLA-4 , Feminino , Citometria de Fluxo , Células Matadoras Naturais/metabolismo , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Baço/patologia , Transfecção
16.
Hum Gene Ther ; 12(2): 149-60, 2001 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-11177552

RESUMO

We have reported that particle-mediated interleukin 12 (IL-12) gene transfer into the skin overlying the local tumor inhibits systemic metastases. To further characterize this effect, we compared the antitumor and antimetastatic effects of IL-12 cDNA delivered at the local tumor site versus at a site distant from the primary tumor, in a spontaneous metastasis model of LLC-F5 tumor. Local IL-12 gene delivery into the skin overlying the intradermal tumor (local IL-12 treatment) on days 7, 9, and 11 after tumor implantation resulted in the most suppression of the growth of the primary LLC-F5 tumor, whereas IL-12 gene transfer into the skin distant from the tumor (distant IL-12 treatment) was less effective. In contrast, both local IL-12 and distant IL-12 treatment, followed by tumor excision, inhibited lung metastases to a similar extent, resulting in significantly extended survival of test mice. The results of in vivo studies using depleting anti-asialo GM1 antibody and anti-CD4/anti-CD8 monoclonal antibodies, or neutralizing anti-interferon gamma (IFN-gamma) monoclonal antibody demonstrated that natural killer (NK) cells, CD8(+) T cells, and IFN-gamma contributed to the antimetastatic effects in both treatment groups. Furthermore, the levels of mRNA expression of vascular endothelial growth factor and matrix methalloproteinase 9 at the tumor microenvironment were suppressed after both local and distant IL-12 treatment. These results suggest that the current particle-mediated IL-12 gene delivery in the spontaneous LLC-F5 metastasis model can confer antimetastatic activities, irrespective of the gene transfection site, via a combination of several mechanisms involving CD8(+) T cells, NK cells, IFN-gamma, and antiangiogenesis.


Assuntos
Técnicas de Transferência de Genes , Neoplasias Pulmonares/prevenção & controle , Neoplasias Experimentais/prevenção & controle , Pele/metabolismo , Animais , Linfócitos T CD8-Positivos/imunologia , Primers do DNA/química , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/metabolismo , Feminino , Expressão Gênica , Terapia Genética , Imunidade Celular , Injeções Intraperitoneais , Interferon gama/metabolismo , Interleucina-12/genética , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Linfocinas/genética , Linfocinas/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Citotóxicos/imunologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
17.
AJR Am J Roentgenol ; 176(3): 789-95, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11222227

RESUMO

OBJECTIVE: This study determined the effect of vascular occlusion on radiofrequency lesion shape, volume, and temperature in a porcine liver model. SUBJECTS AND METHODS: Radiofrequency lesions (n = 33) were created in the livers of six domestic pigs in vivo using a multiprong radiofrequency electrode. Lesions were randomly assigned to one of four vascular occlusion groups: portal vein, hepatic artery, Pringle maneuver (both hepatic artery and portal vein), or no occlusion. Radiofrequency parameters were time, 7 min; power, 50 W; and target temperature, 100 degrees C. Temperatures were measured 5, 10, and 15 mm from the electrode. After the animals were sacrificed, the lesions were excised. Lesion volume, diameter, and shape; maximum temperature; and time exposed to lethal temperatures (42-60 degrees C) were determined. RESULTS: Lesion volume was greatest with the Pringle maneuver lesions (12.6 +/- 4.8 cm(3)), followed by occlusion of the portal vein (8.6 +/- 3.8 cm(3)), occlusion of the hepatic artery (7.6 +/- 2.9 cm(3)), and no occlusion (4.3 +/- 1.0 cm(3)) (p < 0.05). Maximum lesion diameter was similar with the Pringle maneuver (3.3 +/- 0.3 cm), the portal vein (3.3 +/- 0.2 cm), and the hepatic artery (3.2 +/- 0.2 cm) groups compared with no occlusion (2.6 +/- 1.0 cm) (p < 0.05). Minimum lesion diameter ranged from 2.9 cm for Pringle maneuver lesions to 1.0 cm for lesions with no occlusion (p < 0.05). Vascular occlusion increased the time tissue was exposed to lethal temperatures (> 42-60 degrees C) and created more spherical lesions than no occlusion. CONCLUSION: Vascular occlusion combined with radiofrequency ablation increases the volume of necrosis, creates a more spherical lesion, and increases the time tissue is exposed to lethal temperatures when compared with radiofrequency alone. Most of this vascular occlusion effect could be accomplished with hepatic artery occlusion alone.


Assuntos
Ablação por Cateter , Artéria Hepática , Fígado/cirurgia , Veia Porta , Animais , Constrição , Feminino , Fígado/patologia , Suínos , Fatores de Tempo
18.
AJR Am J Roentgenol ; 175(3): 705-11, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10954454

RESUMO

OBJECTIVE: The objective of this study was to compare CT and sonography for monitoring radiofrequency (RF) lesions in porcine livers. SUBJECTS AND METHODS: RF lesions (n = 12) were created in three pig livers by applying 13 min of current to a multielectrode RF probe with a target temperature of 95 degrees C. Helical unenhanced CT and corresponding axial sonography were performed before ablation, at 2 min, 8 min, and immediately after ablation. Contrast-enhanced CT was performed after ablation. CT scans and sonograms were evaluated by blinded observers for conspicuity of the RF lesion, edge detection (visibility of liver-lesion interface), and artifacts. Hounsfield units were recorded at every time interval, and radiologic-pathologic correlation for lesion size and configuration was performed. RESULTS: Mean size of RF lesions was 3. 03 +/- 0.9 cm. On CT, RF lesions had consistently lower attenuation values than surrounding liver (22.2 H lower than liver at 8 min, p < 0.0001). Echogenicity was variable with sonography (hypoechoic = 59%, hyperechoic = 25%, isoechoic = 16%). Unenhanced CT significantly improved conspicuity, edge detection of RF lesions, and decreased artifacts compared with sonography (p < 0.05). Contrast-enhanced CT improved RF lesion detection, border discrimination, and artifacts compared with sonography (p < 0.05). Unenhanced CT had the best correlation to pathologic size (r = 0.74), followed by contrast-enhanced CT (r = 0.72) and sonography (r = 0.56). Contrast-enhanced CT best correlated with lesion shape, but slightly overestimated size because of areas of ischemia peripheral to the RF lesion. CONCLUSION: In this animal model, unenhanced CT was an effective way to monitor RF ablation compared with sonography because of increased lesion discrimination, reproducible decreased attenuation during ablation, and improved correlation to pathologic size.


Assuntos
Hepatectomia/métodos , Cuidados Intraoperatórios/métodos , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Animais , Ablação por Cateter , Fígado/cirurgia , Suínos , Ultrassonografia
19.
Int J Gynecol Pathol ; 19(3): 243-7, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10907173

RESUMO

Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low- and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Metástase Linfática/diagnóstico , Neoplasias Vulvares/patologia , Anticorpos Monoclonais , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Excisão de Linfonodo , Linfonodos/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Vulvares/cirurgia
20.
J Laparoendosc Adv Surg Tech A ; 10(6): 297-304, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11132907

RESUMO

The refinement of minimally invasive surgical techniques has impacted all areas of surgical practice. Laparoscopic approaches to lumbar spine fusion via the transperitoneal and retroperitoneal routes have similarly evolved with the development of new techniques and instruments unique to this procedure. The benefits of laparoscopic fusion techniques include shorter hospital stay, improved postoperative relief of pain, and preservation of critical spinal musculature. A general surgical laparoscopist is a critical member of the operative team. Although the technical details of the procedure are becoming standardized, patient selection is critical to maximize benefit and minimize risk.


Assuntos
Laparoscopia , Fusão Vertebral/métodos , Cirurgia Geral , Humanos
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