RESUMO
BACKGROUND/AIMS: We have reported a clinically meaningful local-control effect and a hepatic metastatic tumor-regression effect of transcatheter peripancreatic arterial embolization-hepatic and splenic arterial infusion chemotherapy (TPPAE-HSAIC) for unresectable advanced pancreatic cancer. The aim of this study was to evaluate the clinical significance, of adjuvant surgical resection after TPPAE-HSAIC. METHODOLOGY: We assessed histopathological findings and outcomes of 6 patients who underwent surgical resection of tumors judged to be radically resectable after attaining tumor down-staging or long-term tumor control following TPPAE-HSAIC for pancreatic cancer initially diagnosed as unresectable. RESULTS: Clinical stage at the initial diagnosis was T4N0M0 Stage III in 4 patients and T4N0M1 Stage IV in 2 patients. The durations of TPPAE-HSAIC ranged from 5 to 46 months with a median of 19 months. An R0 resection was performed in 5 of the 6 patients (83%) and pathological down-staging, from the viewpoint of clinical stage, was observed in 4 patients. Of the 5 patients with R0 resection, one died from a postoperative complication at 7 months and another from pulmonary metastasis at 30 months post-operatively, while the other 3 patients have survived for 45 to 83 months to date. CONCLUSIONS: If surgical resection of pancreatic cancer initially diagnosed as unresectable can be carried out in patients responding favorably to TPPAE-HSAIC, the likelihood of long-term survival might be increased.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , GencitabinaRESUMO
Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.
Assuntos
Fibronectinas/metabolismo , Integrina alfa4beta1/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas Serina-Treonina Quinases , Animais , Anticorpos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Integrina alfa4beta1/efeitos dos fármacos , Integrina alfa4beta1/imunologia , Integrina alfa5beta1/metabolismo , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Camundongos , Camundongos SCID , Neoplasia Residual , Fosfatidilinositol 3-Quinases/metabolismo , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Taxa de Sobrevida , Fatores de Tempo , Células Tumorais CultivadasRESUMO
A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.
Assuntos
Adenocarcinoma Mucinoso/complicações , Carcinoma Ductal Pancreático/complicações , Fístula Pancreática/complicações , Neoplasias Pancreáticas/complicações , Obstrução Ureteral/etiologia , Doença Aguda , Idoso , Humanos , Masculino , Pancreatite/complicaçõesRESUMO
A 78-year-old man had been admitted to a previous hospital because of epigastralgia and a diagnosis of cholecystolithiasis had been made. He had been transferred to our institution for further examination. CT scan and US revealed chronic cholecystitis and gallstone, however, ERC revealed severe obstruction of the cystic duct and EUS revealed dilation of that duct and a solitary mass there. Carcinoma of the cystic duct was diagnosed, and we performed cholecystectomy and resection of the extrahepatic duct with two-field lymphadenectomy. The pathological specimen showed a round flat elevated mass localized in the cystic duct. Histopathologically, the diagnosis was well differentiated tubular adenocarcinoma of the cystic duct with limy bile and tiny gallstone.
Assuntos
Adenocarcinoma/complicações , Neoplasias dos Ductos Biliares/complicações , Colecistolitíase/complicações , Ducto Cístico , Adenocarcinoma/patologia , Idoso , Bile , Neoplasias dos Ductos Biliares/patologia , Colecistectomia , Colecistolitíase/cirurgia , Cálculos Biliares/complicações , Cálculos Biliares/cirurgia , Humanos , MasculinoRESUMO
Administration of imatinib exacerbated psoriasis vulgaris in a case of chronic myelogenous leukemia (CML). After the cessation of imatinib therapy, the psoriasis was alleviated. Upon readministration of imatinib, the psoriasis worsened despite the improvement of hematological and cytogenetic findings in the CML. Psoriasis is known to be an autoimmune skin disease characterized by Th1 cell-mediated hyperproliferation of keratinocytes, and the type 1 helper T (Th1) cell subset increased with imatinib therapy. Thus, the exacerbation of psoriasis was likely due to the increase in Th1 cells associated with imatinib therapy.
Assuntos
Antineoplásicos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Psoríase/induzido quimicamente , Pirimidinas/efeitos adversos , Antineoplásicos/uso terapêutico , Benzamidas , Humanos , Mesilato de Imatinib , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Psoríase/imunologia , Pirimidinas/uso terapêutico , Células Th1/imunologiaRESUMO
We evaluated the effect of biliary endoprotheses for 20 malignant stenosis patients by an expandable metallic stent and hydrophilic heparinized tube (H-PSD) connected to an implantable port (IP), which reduces bacterial adherence. Group A consisted of 6 patients of cholangiocarcinoma who underwent hepatic arterial infusion chemotherapy associated with radiotherapy. Groups B and C consisted of 8 and 6 patients of stage IVa and IVb pancreatic carcinoma, respectively, who underwent hepatic and splenic arterial infusion chemotherapy following transcatheter peripancreatic arterial embolization. The 50% patent time was 12 months, 6 months and 7 months in groups A, B and C and the 50% overall survival time was 16 months, 23 months and 13 months, respectively. There were two complications, 1 case of infection around the IP in which the IP was withdrawn, and 3 cases of cholangitis in which we had easy access to the bile duct via IP. This technique appears to offer significant benefit in selecting patients with this type of biliary obstruction.
Assuntos
Colangiocarcinoma/complicações , Colestase/terapia , Stents , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Stents/efeitos adversos , Resultado do TratamentoRESUMO
We performed intraperitoneal and intrapleural dosing gemcitabine (GEM) to eight patients with advanced pancreatic cancer having peritoneal or pleural carcinomatosis and evaluated its actions and safety. GEM (500 mg/m2) was infused into the abdominal cavity or thoracic cavity after drainage of peritoneal or pleural effusion. We checked the change of serum GEM concentration and the side effects after the GEM administration. Then, we repeated the GEM administration observing their systematic symptoms and evaluated the alteration of peritoneal or pleural effusion and cytology. Plasma concentration of GEM by infusing into the abdominal cavity or thoracic cavity was lower than by intravenous injection. In three of the five cases of peritoneal carcinomatosis, intraperitoneal administration revealed a decrease of peritoneal effusion. In two of the three cases of pleural carcinomatosis, intrapleural administration revealed a decrease of pleural effusion. Four cases had leukocytopenia of grade 1/2, three cases had thrombocytopenia, and two cases had alopecia as side effects, although all of them were minor side effects. Intraperitoneal and intrapleural dosing GEM had minor side effects and could improve QOL for the patients with advanced pancreatic cancer associated with peritoneal or pleural carcinomatosis.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/sangue , Carcinoma/patologia , Carcinoma/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/sangue , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Cavidade Pleural , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/secundário , GencitabinaRESUMO
A 63-year-old woman had previously been admitted to another hospital due to fever, abdominal pain and diarrhea. She was treated with fasting, antibiotics and G-CSF administration because of the coexistence of neutropenia, and the symptoms improved. However, discontinuation of G-CSF administration resulted in a recurrence of the neutropenia accompanied with enterocolitis. After admission to our hospital, a diagnosis for idiopathic AIN was performed as she tested positive in both granulocyte immunofluorescence and granulocyte agglutination tests. Administration of corticosteroid following G-CSF resulted in a continuous increase in the neutrophil count and the disappearance of anti-neutrophil autoantibodies.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Enterocolite/etiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/tratamento farmacológico , Prednisolona/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , RecidivaRESUMO
We treated two chronic phase chronic myelogenous leukemia patients with imatinib mesylate. Hematological complete remission and significant regression of bone marrow fibrosis were observed in both patients. The large amount of TGF-beta produced by increased bone marrow megakaryocytes might have caused the myelofibrosis, and it was revealed that imatinib mesylate brought about regression of the myelofibrosis by reducing the number of megakaryocytes in both patients.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Pirimidinas/uso terapêutico , Idoso , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Masculino , Prognóstico , Indução de RemissãoRESUMO
We previously reported the clinical efficacy based on hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer after transcatheter peripancreatic arterial embolization (TPPAE). However, this medical treatment pointed out a few problems in which the method had its complexity and a limited use of embolus micro-coil numbers. Then, we tried to improve the method in solving those problems. In order to reduce the embolus micro-coil numbers for TPPAE, we divided the micro-coil into several parts. We also devised the method of HSAIC. We used one catheter with a side hole, so that the catheter was able to supply a therapeutic drug for arterial infusion chemotherapy, both to the common hepatic artery and splenic artery. The effective rate for eleven cases was 72.7%, and there were no significant differences from the cases treated with the conventional method of TPPAE-HSAIC. Therefore, the devised treatment was considered to be an easy and useful method for TPPAE and HSAIC.
Assuntos
Embolização Terapêutica/métodos , Neoplasias Pancreáticas/terapia , Cateterismo/métodos , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Artéria EsplênicaRESUMO
A 40-year-old female visited our hospital with general malaise. She was diagnosed with gastric carcinoma with multiple skin, bone, and bilateral ovary metastases. Chemotherapy with 5-FU (1,000 mg/w) and cisplatin (10 mg/w) was performed in the outpatient clinic. Two years after the initial diagnosis, CEA was elevated. She then was given chemotherapy of CPT-11 (40 mg/w) in the outpatient clinic after 1 cycle of combined chemotherapy of CPT-11 and cisplatin. She died 38 months after the initial diagnosis. Weekly 5-FU/CDDP or low-dose CPT-11 appear to be effective for such a gastric carcinoma with systemic metastases without impairing quality of life.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Camptotecina/análogos & derivados , Neoplasias Ovarianas/secundário , Neoplasias Cutâneas/secundário , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Camptotecina/administração & dosagem , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Neoplasias Ovarianas/tratamento farmacológico , Prognóstico , Qualidade de Vida , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Gástricas/patologiaRESUMO
We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.
Assuntos
Angiografia , Embolização Terapêutica/métodos , Neoplasias Pancreáticas/terapia , Tomografia Computadorizada por Raios X , Cateterismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/irrigação sanguíneaRESUMO
We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.
Assuntos
Tumor Carcinoide/tratamento farmacológico , Tumor Carcinoide/secundário , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Amido/administração & dosagem , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Biodegradação Ambiental , Tumor Carcinoide/patologia , Feminino , Artéria Hepática , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Mitomicina/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , GencitabinaAssuntos
Colecistite/complicações , Abscesso do Psoas/etiologia , Idoso , Drenagem , Humanos , Masculino , Abscesso do Psoas/cirurgiaRESUMO
We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioembolização Terapêutica , Desoxicitidina/análogos & derivados , Infusões Intra-Arteriais , Neoplasias Pancreáticas/terapia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Desoxicitidina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/secundário , Masculino , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , GencitabinaRESUMO
Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft-versus-host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)-beta from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF-beta concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF-beta concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells.
Assuntos
Doença Enxerto-Hospedeiro/complicações , Trombocitopenia/etiologia , Trombopoetina/análise , Adulto , Medula Óssea/química , Doença Crônica , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia/complicações , Leucemia/terapia , Contagem de Plaquetas , Trombopoetina/sangue , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/sangueRESUMO
The degree of acute graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been observed to be, unexpectedly, of an equal level to that after bone marrow transplantation. To explain this phenomenon, we hypothesized that granulocyte-colony stimulating factor (G-CSF) administration may induce transforming growth factor (TGF)-beta producing T cells in the donors. Five donors received 10 microg/kg G-CSF subcutaneously for 4 days. The TGFbeta mRNA expression in CD4(+) cells as measured by real time reverse transcription-polymerase chain reaction increased after G-CSF administration. This elevation is considered to be one additive mechanism of repression of acute GVHD after allo-PBSCT.
Assuntos
Doadores de Sangue , Linfócitos T CD4-Positivos/metabolismo , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Fator de Crescimento Transformador beta/genética , Linfócitos T CD4-Positivos/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Contagem de Linfócitos , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th1 , Células Th2 , Transplante HomólogoRESUMO
Obliteration of portal-systemic shunts is effective for portosystemic encephalopathy but is often associated with complications such as retention of ascites and worsening of esophageal varices. Selective embolization of the splenic vein was performed on six patients with hepatic encephalopathy and splenorenal shunts. Hepatic encephalopathy was not observed in four patients after the procedure. Neither retention of ascites nor rupture of esophageal varices was observed because postoperative elevation of portal venous pressure was not as great as that seen when shunt obliteration is performed. This procedure can be an effective and safe treatment option for hepatic encephalopathy with a splenorenal shunt.