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1.
World J Surg Oncol ; 14(1): 14, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26791083

RESUMO

BACKGROUND: The aim of current study is to verify usefulness of staging laparoscopy (stag-lap) for patient's selection and to find prognostic factors in patients with radiographically defined locally advanced (RD-LA) pancreatic ductal adenocarcinoma (PDAC). METHODS: The LA disease was defined as an unresectable disease without distant organ metastasis based on resectability status of NCCN guideline in this study. Stag-lap was performed in 67 patients with RD-LA (2007-2012) which were divided into 4 groups according to metastatic site: group CY (peritoneal fluid or washing cytology positive and without any distant organ metastasis); group P (peritoneal dissemination); group L (liver metastasis); group LA (peritoneal fluid or washing cytology negative and without any distant organ metastasis). Clinical backgrounds, survival curves, and prognostic factors were investigated. RESULTS: There were 16 patients in CY group (24%), 13 patients in P group (19%), 10 patients in L group (15%), and 28 patients in LA group (42%). Median survival time was 13 months in CY group and 11 months in LA group, which was significantly better than 7 months in P group, respectively (p<0.05). The rate of emergence of ascites in LA was significantly better than in CY or P groups (p<0.05). Multivariate analysis showed that the presence of partial response and administration of second-line chemotherapy were significantly independent prognostic factors. CONCLUSIONS: The majority of PDAC patients with RD-LA had occult distant organ metastasis. Clinical features and survival curves were different depending on the site of occult distant organ metastasis. Administration of second-line chemotherapy and responsiveness to chemotherapy were associated with favorable prognosis. Staging laparoscopy should be routinely performed in patients with RD-LA PDAC (UMIN000019936).


Assuntos
Carcinoma Ductal Pancreático/patologia , Laparoscopia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Radiografia , Estudos Retrospectivos , Análise de Sobrevida
2.
J Gastroenterol Hepatol ; 29(2): 403-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23869919

RESUMO

BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Desoxicitidina/análogos & derivados , Cuidados Paliativos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tegafur/administração & dosagem , Resultado do Tratamento , Uracila/administração & dosagem , Gencitabina
3.
JOP ; 14(6): 664-8, 2013 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-24216557

RESUMO

CONTEXT: Lymphoepithelial cysts of the pancreas are a rare disease of true pancreatic cysts, the cause of which is unknown. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. CASE REPORT: The present case report is a lymphoepithelial cyst of the pancreas that was resected laparoscopically. A 53-year-old man was incidentally found to have a cystic tumor in the tail of the pancreas after undergoing an abdominal ultrasound, which showed a 41x33 mm cystic mass in the pancreatic tail. He had no abdominal symptoms. Laparoscopic distal pancreatectomy and splenectomy were performed. Histologic examination revealed a lymphoepithelial cyst. CONCLUSION: Herein, we discuss the diagnostic difficulties and management decisions that face surgeons treating pancreatic cysts.


Assuntos
Pâncreas/cirurgia , Pancreatectomia/métodos , Cisto Pancreático/cirurgia , Diagnóstico Diferencial , Epitélio/patologia , Humanos , Laparoscopia , Tecido Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Cisto Pancreático/diagnóstico
4.
J Surg Res ; 173(2): 299-308, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21195425

RESUMO

OBJECTIVE: Pancreatic cancer is a malignant neoplasm with poor prognosis that might be associated with defective immune function. We aimed to determine the influence on survival of circulating myeloid dendritic cells (c-m-DCs), circulating lymphoid DCs (c-l-DCs), and DCs within the tumor tissue in patients with pancreatic cancer. PATIENTS AND METHODS: Between December 2001 and June 2006, of a total of 110 patients with ductal adenocarcinoma of the pancreas, 42 underwent pancreatectomy, and 68 had unresectable disease. Numbers of c-m-DCs and c-l-DCs were assessed by flow cytometry, and DCs in the tumor tissue by immunohistochemical staining with anti-fascin mAb. RESULTS: The percentage of the c-m-DCs subset in pancreatic cancer patients was significantly lower than in healthy volunteers, and the similar finding was observed between patients who underwent surgical resection and non-resection. Patients with a high percentage of c-m-DCs or with many DCs accumulated in the cancer tissue survived longer than patients with a low percentage or low number in peripheral blood or the tumor, respectively. Moreover, there was a positive correlation between c-m-DCs within peripheral blood mononuclear cells and the number of DCs per field in the cancer tissue. CONCLUSIONS: Preoperative c-m-DCs levels in the PBMC of patients with pancreatic cancer and DCs counts in the cancer tissue can be a prognostic factor after surgical resection. Modulating the distribution of DCs may be an effective therapy in pancreatic cancer patients with a dismal prognosis.


Assuntos
Adenocarcinoma/imunologia , Células Dendríticas/patologia , Neoplasias Pancreáticas/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Análise de Sobrevida
5.
Liver Transpl ; 17(12): 1457-66, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21850691

RESUMO

Ischemia/reperfusion (I/R) injury in liver grafts, which is initiated by cold preservation and is augmented by reperfusion, is a major problem that complicates graft quality, posttransplant patient care, and outcomes of liver transplantation (LT). Kupffer cells (KCs) play important roles in I/R injury; however, little is known about their changes during cold preservation. We examined whether a pretreatment with carbon monoxide (CO), a cytoprotective product of heme degradation, could influence KC activity during cold storage and protect liver grafts against LT-induced I/R injury. In vitro, primary rat KCs were stimulated for 24 hours under hypothermic conditions (4°C, 20% O(2)), with lipopolysaccharide, or under hypoxic conditions (37°C, 5% O(2)) with or without a CO pretreatment. When rat KCs were exposed to hypothermic conditions, they produced reactive oxygen species (ROS), but they did not produce tumor necrosis factor α (TNF-α) or nitric oxide. The preincubation of KCs with CO up-regulated heat shock protein 70 (HSP70) and inhibited ROS generation. When liver grafts from donor rats exposed to CO (250 ppm) for 24 hours were transplanted after 18 hours of cold preservation in University of Wisconsin solution, HSP70 expression increased in these grafts versus control grafts, and serum aspartate aminotransferase and alanine aminotransferase levels as well as necrotic areas and inflammatory infiltrates were significantly reduced after LT. CO-pretreated liver grafts showed less up-regulation of TNF-α and inducible nitric oxide synthase messenger RNA (mRNA) and reduced expression of proapoptotic B cell lymphoma 2-associated X protein mRNA, cleaved caspase-3, and poly(adenosine diphosphate ribose) polymerase. In conclusion, the pretreatment of donors with CO ameliorates LT-associated I/R injury with increased hepatic HSP70 expression, particularly in the KC population.


Assuntos
Monóxido de Carbono/administração & dosagem , Isquemia Fria/efeitos adversos , Células de Kupffer/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Substâncias Protetoras/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Administração por Inalação , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Citoproteção , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP70/metabolismo , Mediadores da Inflamação/metabolismo , Células de Kupffer/metabolismo , Células de Kupffer/patologia , Masculino , Necrose , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética
6.
Med Mol Morphol ; 43(4): 235-40, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21267701

RESUMO

Primary splenic mucinous cystadenocarcinoma (MCCa) is extremely rare, and only six cases appear to have been reported previously. We present herein a case of primary splenic MCCa resulting in pseudomyxoma peritonei (PMP). A 66-year-old Japanese woman presented to a hospital with a chief complaint of upper abdominal pain and a 7-year history of splenic cyst. Cyst rupture was noted on computed tomography, and splenectomy was performed. The abdominal cavity was filled with a large amount of gelatinous ascites, with the appearance of PMP. On the cut surface, multiple cysts containing mucinous material were found within and outside the spleen. Microscopically, splenic parenchyma was occupied by large mucinous pools focally lined with mucinous epithelial cells and mesothelial cell-like cells, which were considered benign. Outside the spleen, a low-grade MCCa component was found. No ectopic pancreatic or intestinal tissue was identified. Although most PMP cases are known to be caused by low-grade mucinous appendiceal tumor, the present case represents the first report of a splenic MCCa resulting in PMP.


Assuntos
Cistadenocarcinoma Mucinoso/patologia , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Neoplasias Esplênicas/patologia , Idoso , Cistadenocarcinoma Mucinoso/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia , Esplenectomia/métodos , Neoplasias Esplênicas/cirurgia
7.
Gan To Kagaku Ryoho ; 37(12): 2271-3, 2010 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-21224544

RESUMO

We explored the outcome of the multi-disciplinary management for obtaining long-term survivors in patients with pancreatic cancer that extended beyond the pancreas. This single-institution experience indicates that surgical resection following the neoadjuvant chemoradiation (NACRT) therapy is able to increase the resectability rate with clear margins and to decrease the rate of metastatic lymph nodes, resulting in improved prognosis of curative cases with pancreatic cancer that extended beyond the pancreas.


Assuntos
Neoplasias Pancreáticas/terapia , Idoso , Feminino , Humanos , Metástase Linfática/prevenção & controle , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Prognóstico
8.
Stem Cells ; 26(2): 330-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17975222

RESUMO

Following transplantation of green fluorescent protein (GFP)-labeled bone marrow (BM) into irradiated, wild-type Sprague-Dawley rats, propagated GFP(+) cells migrate to adipose tissue compartments. To determine the relationship between GFP(+) BM-derived cells and tissue-resident GFP(-) cells on the stem cell population of adipose tissue, we conducted detailed immunohistochemical analysis of chimeric whole fat compartments and subsequently isolated and characterized adipose-derived stem cells (ASCs) from GFP(+) BM chimeras. In immunohistochemistry, a large fraction of GFP(+) cells in adipose tissue were strongly positive for CD45 and smooth muscle actin and were evenly scattered around the adipocytes and blood vessels, whereas all CD45(+) cells within the blood vessels were GFP(+). A small fraction of GFP(+) cells with the mesenchymal marker CD90 also existed in the perivascular area. Flow cytometric and immunocytochemical analyses showed that cultured ASCs were CD45(-)/CD90(+)/CD29(+). There was a significant difference in both the cell number and phenotype of the GFP(+) ASCs in two different adipose compartments, the omental (abdominal) and the inguinal (subcutaneous) fat pads; a significantly higher number of GFP(-)/CD90(+) cells were isolated from the subcutaneous depot as compared with the abdominal depot. The in vitro adipogenic differentiation of the ASCs was achieved; however, all cells that had differentiated were GFP(-). Based on phenotypical analysis, GFP(+) cells in adipose tissue in this rat model appear to be of both hematopoietic and mesenchymal origin; however, infrequent isolation of GFP(+) ASCs and their lack of adipogenic differentiation suggest that the contribution of BM to ASC generation might be minor.


Assuntos
Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Transplante de Medula Óssea , Proteínas de Fluorescência Verde/metabolismo , Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Animais , Animais Geneticamente Modificados , Antígenos CD/metabolismo , Diferenciação Celular , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Fenótipo , Quimera por Radiação , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo
9.
Hepatogastroenterology ; 56(90): 529-34, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19579636

RESUMO

BACKGROUND/AIMS: Accurate pre-operative staging in patients with pancreatic cancer is crucial for avoiding unnecessary laparotomy and for selecting patients accurately for curative resection. In this study, tumor resectability and residual tumor grading in patients evaluated by MD-CT (Multi-detector row CT) or by SD-CT (single-detector CT) were compared to determine whether more accurate imaging has a significant clinical impact on patient selection and surgical outcomes. METHODOLOGY: One hundred-fifty consecutive patients with pancreatic cancer evaluated from January 2000 to April 2005 were included in this retrospective study. Seventy pancreatic cancer patients underwent pre-operative evaluation using SD-CT and angiography (5-7 mm slice thickness, 1st period 2000-2002), and 80 patients underwent MD-CT (1.25 mm slice thickness, 2nd period 2002-2005). RESULTS: The introduction of MD-CT had a significant impact on the selection of suitable patients, this group showing a lower frequency of surgical intervention in cases of incurable disease (p = 0.0383). Pre-operative evaluation using MD-CT in the resected cases also provided a higher percentage of accurate R0/R1 grading relative to SD-CT evaluations (p = 0.0164). CONCLUSION: MD-CT imaging has a significant impact on preventing unnecessary exploratory surgery and on the selection of appropriate pancreatic cancer patients for surgical resection.


Assuntos
Neoplasias Pancreáticas/diagnóstico por imagem , Seleção de Pacientes , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Análise de Sobrevida
10.
Liver Transpl ; 14(3): 346-57, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18306376

RESUMO

The interaction of donor passenger leukocytes and host leukocytes in recipient secondary lymphoid tissues during the early posttransplantation period is crucial in directing host immune reactions toward allograft rejection or acceptance. Responsible T cell clones could be activated through the direct and indirect pathways of allorecognition. We examined the role of the indirect pathway in liver transplantation (LT) tolerance by depleting host antigen-presenting cells (APC) with phagocytic activity [e.g., cluster domain (CD)68+/CD163+ macrophages, CD11c+ dendritic cells (DC)] using liposome-encapsulating clodronate (LP-CL). After Lewis rat cell or liver graft transplantation, Brown Norway (BN) rat recipients pretreated with LP-CL showed a significantly reduced type 1 helper T cell cytokine up-regulation than control-LP-treated recipients. In the LT model, LP-CL treatment and host APC depletion abrogated hepatic tolerance; Lewis liver grafts in LP-CL-treated-BN recipients developed mild allograft rejection, failed to maintain donor major histocompatibility complex (MHC) class II+ leukocytes, and developed chronic rejection in challenged donor heart allografts, while control-LP-treated BN recipients maintained tolerance status and donor MHC class II+ hepatic leukocytes. Furthermore, in the BN to Lewis LT model, LP-CL recipient treatment abrogated spontaneous hepatic allograft acceptance, and graft survival rate was reduced to 43% from 100% in the control-LP group. In conclusion, the study suggests that host cells with phagocytic activity could play significant roles in developing LT tolerance.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Tolerância Imunológica/imunologia , Transplante de Fígado/imunologia , Tolerância ao Transplante/imunologia , Animais , Células Apresentadoras de Antígenos/patologia , Ácido Clodrônico/administração & dosagem , Células Dendríticas/imunologia , Células Dendríticas/patologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Leucócitos/imunologia , Leucócitos/patologia , Lipossomos , Transplante de Fígado/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Fagocitose/imunologia , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew
11.
Asian Pac J Cancer Prev ; 19(7): 1753-1759, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30049183

RESUMO

Objective: The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods: This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results: Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma.Conclusions: Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Fluordesoxiglucose F18 , Doenças Profissionais/patologia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Adulto , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/epidemiologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/epidemiologia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico por imagem , Doenças Profissionais/epidemiologia , Prognóstico
12.
Cancer Chemother Pharmacol ; 81(3): 461-468, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29305639

RESUMO

PURPOSE: To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. METHODS: A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m2) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2). RESULTS: Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confirmed as the maximum tolerated dose and Level - 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group. CONCLUSIONS: Level - 2 was confirmed as the RD (GEM 800 mg/m2 and S-1 50 mg/m2) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy.


Assuntos
Neoplasias do Sistema Biliar/tratamento farmacológico , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Desoxicitidina/análogos & derivados , Monitoramento de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ácido Oxônico , Tegafur , Administração Intravenosa , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Quimioterapia Adjuvante/métodos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/farmacocinética , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/farmacocinética , Resultado do Tratamento , Gencitabina
13.
Circulation ; 112(4): 587-91, 2005 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-16027253

RESUMO

BACKGROUND: Autologous vein grafts and balloon angioplasty are still commonly used for arterial reconstructive procedures. Their success is limited by the development of intimal hyperplasia (IH). Biliverdin (BVD), one of the by-products of heme degradation, has been shown to have potent antioxidant and antiinflammatory effects. We hypothesized that BVD administration would protect vascular tissue against vascular injury. METHODS AND RESULTS: The effects of BVD administration against IH after vascular injury were analyzed in an arterialized vein graft model and a balloon injury model in rats. BVD treatment significantly suppressed the development of IH in both models compared with those without BVD. The mechanisms by which BVD treatment inhibits IH development might include decreasing c-Jun NH2 terminal kinase activation and preventing apoptosis of endothelial cells. BVD also suppressed vascular smooth muscle cell migration in vitro. CONCLUSIONS: BVD administration prevented IH associated with arterialized vein graft vasculopathy or balloon angioplasty-induced vessel injury. These results suggest that a treatment regimen with exogenous BVD administration could provide an effective therapeutic adjunct to facilitate transfer of experimental treatments for vascular injury to the clinic.


Assuntos
Biliverdina/farmacologia , Túnica Íntima/patologia , Doenças Vasculares/tratamento farmacológico , Animais , Apoptose , Movimento Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Hiperplasia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Fosforilação , Ratos , Ratos Endogâmicos Lew , Doenças Vasculares/patologia
14.
Transplantation ; 81(3): 438-44, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16477232

RESUMO

BACKGROUND: Unequivocal eradication of donor leukocyte microchimerism from recipients of long-surviving organ transplants has never been reported. Here we describe a drastic attempt to accomplish this objective. METHODS: In control experiments, a rank order of microchimerism and of associated donor specific nonreactivity was produced in Brown-Norway (BN) rats by transplantation of Lewis (LEW) liver, bone marrow cell (BMC) and heart allografts under a brief course of tacrolimus. The degree of microchimerism at 60 and 110 days was estimated with semiquanitative immunocytochemical and PCR techniques. Tolerance at 110 days was assessed in the different control groups by challenge transplantation of naïve LEW hearts. In parallel experimental groups, an attempt was made to eliminate microchimerism from the BN recipients. The animals were submitted at 60 days to 9.5-Gy total body irradiation (TBI), reconstituted immediately with naïve BN BMC, and tested for donor specific nonreactivity by LEW heart transplantation at 110 days. RESULTS: After the TBI-reconstitution at 60 days, microchimerism was undetectable in BMC recipients at 110 days, significantly reduced in heart recipients, and least affected in liver recipients. Except in liver recipients, abrogation of LEW-specific nonreactivity was demonstrated by rejection of the priming grafts, or by rejection of the challenge heart grafts, and by in vitro immune assay. CONCLUSIONS: It is difficult to eliminate microchimerism in organ recipients once the donor cells have settled into tissue niches.


Assuntos
Leucócitos , Transplante de Órgãos , Quimeras de Transplante , Animais , Células da Medula Óssea/patologia , Células da Medula Óssea/efeitos da radiação , Transplante de Medula Óssea , DNA/análise , Feminino , Rejeição de Enxerto/patologia , Coração/efeitos da radiação , Transplante de Coração , Leucócitos/química , Leucócitos/imunologia , Leucócitos/efeitos da radiação , Fígado/patologia , Fígado/efeitos da radiação , Transplante de Fígado , Teste de Cultura Mista de Linfócitos , Masculino , Miocárdio/patologia , Quimera por Radiação , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Tolerância ao Transplante , Transplante Homólogo , Irradiação Corporal Total
15.
Transplantation ; 81(2): 220-30, 2006 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-16436966

RESUMO

BACKGROUND: Carbon monoxide (CO), a byproduct of heme catalysis, has lately received considerable attention as a regulatory molecule in cellular and biological processes. CO has been shown to provide potent protection against a variety of tissue injuries. We hypothesized in this study that low concentration CO would be beneficial for organ allografts, which frequently undergo several types of injury such as ischemia/reperfusion, alloimmune reaction, and inflammation METHODS: The efficacy of low-dose CO was examined in a fully allogeneic LEW to BN rat heterotopic heart transplantation (HHTx) model. Recipients were kept in air or exposed to low-dose CO (20 ppm) for 14, 28, or 100 days after HHTx under short-course tacrolimus RESULTS: CO treatment (d0-28, 0-100) was remarkably effective in prolonging heart allograft survival to a median of >100 from 45 days in the air-control group, with significant reductions of arteritis, fibrosis, and cellular infiltration, including macrophages and T cells. CO inhibited intragraft upregulation of Th1 type cytokines (IL-2, IFNgamma), proinflammatory mediators (IL-1beta, TNFalpha, IL-6, COX-2), and adhesion molecule. Shorter CO exposure in early (0-13d) and late (14-28d) posttransplant periods also prolonged graft survival, with a significant inhibition of inflammatory mediators CONCLUSIONS: These results show that low dose CO inhalation protects heart allografts and can considerably prolong their survival. CO appears to function via multiple mechanisms, including direct inhibition of Th1 type cytokine production and regulation of inflammatory responses.


Assuntos
Monóxido de Carbono/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Transplante de Coração/imunologia , Transplante de Coração/métodos , Mediadores da Inflamação/metabolismo , Linfócitos T/imunologia , Administração por Inalação , Animais , Sequência de Bases , Citocinas/genética , DNA/genética , Transplante de Coração/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Fatores de Tempo , Transplante Homólogo
16.
Surgery ; 138(2): 229-35, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16153431

RESUMO

BACKGROUND: Carbon monoxide (CO), a product of heme degradation by heme oxygenase, induces cytoprotection against ischemia/reperfusion (I/R) injury in a variety of organs such as the heart, lung, kidney, and small intestine. We examined whether CO would protect liver grafts against cold I/R injury associated with transplantation. METHODS: Orthotopic liver transplantation (OLT) was performed in syngeneic Lewis rats with 18 hours preservation in cold University of Wisconsin solution. Recipients were exposed to air or CO (100 ppm) for 1 hour before and 24 hours after OLT. Recipients were sacrificed 0.5 to 48 hours post-transplant. RESULTS: CO inhalation significantly decreased serum aspartate aminotransferase and alanine aminotransferase levels and suppressed hepatic necrosis formation and neutrophil accumulation at 6 to 48 hours after OLT, compared with air control. The expressions of tumor necrosis factor alpha, intercellular adhesion molecule 1, and inducible nitric oxide synthase messenger RNA in the liver graft were significantly inhibited in the CO-treated group at 1 hour after reperfusion. Hepatic nuclear factor-kappaB activation did not differ between the groups. CONCLUSIONS: The results demonstrate that exogenous CO treatment suppresses early proinflammatory gene expression and neutrophil infiltration, and efficiently ameliorates hepatic I/R injury. The possible mechanism by which CO protects the liver against cold I/R does not seem to be associated with downregulation of the nuclear factor-kappaB-signaling pathway.


Assuntos
Monóxido de Carbono/farmacologia , Criopreservação , Transplante de Fígado , Traumatismo por Reperfusão/tratamento farmacológico , Administração por Inalação , Animais , Monóxido de Carbono/sangue , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Hemoglobinas/metabolismo , Molécula 1 de Adesão Intercelular/genética , Masculino , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
17.
Intern Med ; 54(21): 2711-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26521898

RESUMO

A 74-year-old man was diagnosed with small cell carcinoma arising from the extrahepatic bile duct according to a histological examination of the biopsy specimen obtained during endoscopic retrograde cholangiopancreatography. Additionally, bulky hilar lymphadenopathy was observed, and the patient was treated with the combination of radiation and chemotherapy (cisplatin and irinotecan). Post-therapy, he underwent pancreaticoduodenectomy. The histological examination of the resected specimen revealed no residual cancer cells in the bile duct wall and a small amount of cancer cells in only a single lymph node. Due to this multidisciplinary therapy, the patient showed no signs of recurrence 12 months postoperatively.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Extra-Hepáticos , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/terapia , Ducto Colédoco/patologia , Pancreaticoduodenectomia , Idoso , Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/radioterapia , Ductos Biliares Extra-Hepáticos/diagnóstico por imagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Colangiopancreatografia Retrógrada Endoscópica , Cisplatino/administração & dosagem , Humanos , Irinotecano , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Pancreaticoduodenectomia/métodos , Radiossensibilizantes/administração & dosagem , Resultado do Tratamento
18.
Exp Biol Med (Maywood) ; 228(6): 724-9, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12773705

RESUMO

The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.


Assuntos
Raios Infravermelhos/uso terapêutico , Pele/efeitos da radiação , Cicatrização/efeitos da radiação , Animais , Colágeno/análise , Colágeno/ultraestrutura , Modelos Animais de Doenças , Fibroblastos/química , Fibroblastos/metabolismo , Hipertermia Induzida/métodos , Imuno-Histoquímica/métodos , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Pele/citologia , Pele/metabolismo , Temperatura Cutânea/efeitos da radiação , Fator de Crescimento Transformador beta/metabolismo
19.
Anticancer Res ; 22(4): 2137-45, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12174895

RESUMO

The effects of biological response modifiers (BRMs) on the functions of two types of dendritic cells (DCs) were examined in relation to anti-tumor therapy. The two BRMs studied in our assay system were OK432 (a streptococcal preparation) and KP-40 (Propionibacterium avidum: a heat-inactivated bacterial vaccine). Recently, techniques for isolating human DCs from peripheral blood have been established, and DCs can be divided into two subsets: CD11c+ DCs (myeloid DC population) and CD11c- DCs (lymphoid DC population). Both OK432 and KP-40 were found to up-regulate the activity of myeloid-lineage DCs: the expression of major histocompatibility complex (MHC) class II molecules and adhesion/costimulatory molecules increased, and the production of IL-12 also increased. Therefore, DCs pulsed with OK432 and KP-40 could be applied to vaccination as a new adjuvant for specific immunotherapies.


Assuntos
Adjuvantes Imunológicos/farmacologia , Dendritos/imunologia , Picibanil/farmacologia , Vacinas de Produtos Inativados/farmacologia , Anticorpos Monoclonais , Antígenos CD/análise , Antígenos CD/imunologia , Vacinas Bacterianas , Células Cultivadas , Dendritos/efeitos dos fármacos , Citometria de Fluxo , Humanos
20.
J Hepatobiliary Pancreat Sci ; 21(7): 473-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24339364

RESUMO

BACKGROUND: The most common postoperative complication after distal pancreatectomy (DP) is still postoperative pancreatic fistula (POPF), which is closely associated with other major complications and remains an unsolved problem. METHODS: This retrospective study included 47 consecutive patients who underwent a distal pancreatectomy with (DP-PG group, n = 21) or without (DP group, n = 26) duct-to-mucosa pancreaticogastrostomy from June 2010 to May 2012. Clinical data including POPF-related complications (POPF, fluid collection, intra-abdominal abscess, bleeding and delayed gastric emptying) as a primary endpoint were compared between the two groups. RESULTS: The frequencies of POPF-related complications as well as overall POPF and complications in the DP-PG group were lower than in the DP group (P = 0.037, P < 0.001, respectively). The 30 days morbidity after hospital discharge in the DP-PG group was less than in the DP group (P = 0.014). In both groups median hospital stay was similar. Although additional time needed for pancreaticogastrostomy was 35 (20-55) min, there was no difference in operative times. Patients in the DP group had a higher medical cost for hospitalization than the DP-PG group (P = 0.048). CONCLUSION: Pancreaticogastrostomy as an additional procedure following distal pancreatectomy was associated with a reduced rate of POPF-related complications that resulted in relatively lower medical cost for hospitalization.


Assuntos
Gastrostomia/métodos , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/complicações , Adulto , Idoso , Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
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