RESUMO
BACKGROUND: The primary end points of this study were to determine the dose-limiting toxic effects (DLTs), maximum tolerated dose, and a recommended phase II dose of a synthetic serine protease inhibitor, nafamostat mesilate, in combination with full-dose gemcitabine in patients with unresectable locally advanced or metastatic pancreatic cancer. The secondary end point was to assess therapeutic response. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer received gemcitabine (1 000 mg/m(2) i.v. for 30 min) on days 1, 8, and 15, with nafamostat mesilate (continuous regional arterial infusion for 24 h through a port-catheter system) on days 1, 8, and 15; this regimen was repeated at 28-day intervals. The initial dose of nafamostat mesilate was 2.4 mg/kg and was escalated in increments of 1.2 mg/kg until a dose of 4.8 mg/kg was achieved. A standard '3+3' phase I dose-escalation design was used. Therapeutic response and clinical benefit response were assessed. RESULTS: Twelve patients were enrolled in this study. None of the patients experienced DLTs, and nafamostat mesilate was well tolerated at doses up to 4.8 mg/kg in combination with full-dose gemcitabine. This combination chemotherapy yielded a reduction of a high serum level of the tumor marker CA19-9. Pain was reduced in three of seven patients without oral morphine sulfate. Overall survival was 7.1 months for all patients. CONCLUSION: This phase I study was carried out safely. This combination chemotherapy showed beneficial improvement in health-related quality of life. The recommended phase II dose of nafamostat mesilate in combination with full-dose gemcitabine is 4.8 mg/kg.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Guanidinas/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidinas , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Desoxicitidina/uso terapêutico , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Guanidinas/química , Humanos , Infusões Intra-Arteriais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estrutura Molecular , Indução de Remissão , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Liver failure often develops after extensive liver resection. Preoperative portal vein embolization to induce compensatory hypertrophy in the predicted remnant liver decreases clinical complications after hepatectomy. The aim of this study was to examine whether hyperbaric oxygenation (HBO) after portal vein embolization increases compensatory hypertrophy of the predicted liver remnant. We performed portal vein ligation and HBO in rats to investigate whether HBO after portal vein embolization increases compensatory hypertrophy of the predicted remnant liver. METHODS: Rats were divided into four groups that underwent (1) laparotomy only (control group); (2) right portal vein ligation (RPL group); (3) RPL followed by HBO at 2 atm (HBO-2 atm group; 1 h/day, 5 days/week for 2 weeks); or (4) RPL followed by HBO at 3 atm (HBO-3 atm group). Laparotomy was repeated after 2 weeks in each group; serum levels of albumin and hepatocyte growth factor (HGF) were measured, and the ratio of the weights of nonligated to ligated hepatic segments and the percentage of hepatocytes expressing proliferating cell nuclear antigen (PCNA) in ligated hepatic segments were determined. RESULTS: In rats that had received HBO after RPL, serum levels of HGF, weight ratios of nonligated to ligated hepatic segments, and the percentage of PCNA-positive hepatocytes in nonligated liver were significantly higher than those in the control group. Furthermore, rats that had undergone 3-atm HBO after RPL had significantly higher serum levels of HGF and percentages of PCNA-positive hepatocytes in nonligated hepatic segments. CONCLUSIONS: Preoperative HBO after portal vein embolization may be useful for inducing compensatory hypertrophy of the predicted remnant liver.
Assuntos
Embolização Terapêutica , Oxigenoterapia Hiperbárica , Regeneração Hepática , Fígado/fisiologia , Veia Porta , Animais , Fator de Crescimento de Hepatócito/sangue , Hepatócitos/química , Ligadura , Fígado/irrigação sanguínea , Fígado/cirurgia , Falência Hepática/prevenção & controle , Masculino , Tamanho do Órgão , Complicações Pós-Operatórias/prevenção & controle , Antígeno Nuclear de Célula em Proliferação/análise , Ratos , Ratos Sprague-Dawley , Albumina SéricaRESUMO
We took culture of throat swab from 77 subjects who were negative for infection of HBV, HCV, HIV and syphilis infection before and after endoscopy. Moreover, the existence of bacterium including Helicobacter pylori at overcoat of endoscopic instrument was investigated right after examination and after disinfection of endoscope. Povidoneiodine, 70% alcohol and 1% benzalkonium chloride was used as a disinfectant for endoscope, and it took less than 10 minutes to wash by hand to disinfection. alpha-haemolytic streptococci, Staphylococcus epidermids, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Candida, Pseudomonas aeruginosa and MRSA were cultured in throat swab. The rate of adhesion of bacterium especially such as Candida, K. pneumoniae and S. epidermids to endoscope was considerably high. 23 of 77 subjects had H. pylori infection, and the adhesion of H. pylori to endoscope was found to be 65.2% of the subjects. On the contrast, no bacterium was detected from the endoscopic instrument after careful disinfection. These findings stress the importance of postoperative disinfection of the endoscope to prevent the chance to acquire bacterial infection.