RESUMO
BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/patologia , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Vômito/induzido quimicamente , Vômito/patologia , GencitabinaRESUMO
AIMS: To evaluate the efficacy of reduction hepatectomy followed by transcatheter arterial chemoembolization (TACE) for advanced T-Staged hepatocellular carcinomas (HCCs). METHODS: A retrospective analysis of 39 consecutive patients who underwent reduction hepatectomy followed by TACE for advanced T-Staged HCCs was undertaken. RESULTS: Reduction hepatectomies, including 20 major ones, were performed. After a median interval of 30 days, the hepatectomies were followed by TACE using farmorubicin. Actual overall 3-year survival after surgery was 32%. Indocyanine green R(15) > or =15%, preoperative AFP > or =2000 ng/ml, and tumour reduction rate <98% were predictive of decreased overall survival. When the three prognostic factors were used in a scoring system, with one point assigned for each factor, the 3-year survival rates of patients with scores of 0, 1, 2, and 3 were 71%, 40%, 0%, and 0% respectively. CONCLUSIONS: Reduction hepatectomy followed by TACE is effective in patients with advanced T-Staged HCCs who have none of the 3 poor prognostic factors. Reduction surgery followed by TACE is one of the options for controlling advanced T-Staged HCCs in patients who are not candidates for curative resection or TACE alone.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Quimioterapia Adjuvante , Epirubicina/administração & dosagem , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , alfa-Fetoproteínas/análiseRESUMO
AIMS: The efficacy of surgical resection for multiple colorectal hepatic metastases (MCHM) has been controversial. We examined the survival of patients who received surgery for MCHM and examined the factors associated with survival. METHODS: A retrospective analysis was performed of 50 consecutive patients who received hepatic resections for MCHM, defined as four or more metastatic lesions of colorectal cancer. RESULTS: Overall survival after hepatic resection for MCHM was 48% at 3years and 43% at 5years (median survival, 22.3months). Multivariate analyses revealed that a coefficient of variation (CV) in volume of hepatic metastases in each individual patient above 1.8 (P=0.01, HR=4.08, 95% CI=1.33-12.5) was the only poor prognostic factor after resection of MCHM. CONCLUSIONS: A CV in volume of hepatic metastases in each individual patient above 1.8 predicts poor survival after hepatectomy of MCHM. Thus, the CV in volume of hepatic metastases in each individual patient might be useful in planning the therapeutic strategy for patients with MCHM.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Taxa de SobrevidaRESUMO
We report partial pancreatic head resection of intraductal papillary mucinous carcinoma originating in a branch of the duct of Santorini. The tumor was located in the ventral part of pancreatic head at a distance from the Wirsung duct. Magnetic resonance cholangiopancreatography accurately showed the communication between the duct of Santorini and the cystic tumor, and was useful for determining the part of the pancreas to be resected. Both the duct of Wirsung and the duct of Santorini were preserved. Partial pancreatic head resection would play an important role in surgical management of low-grade malignant neoplasm.
Assuntos
Adenocarcinoma Mucinoso/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/cirurgia , Ductos Pancreáticos/cirurgia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatectomia/métodos , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologiaRESUMO
BACKGROUND: Partial pancreatic head resection has been recommended for intraductal papillary mucinous tumor (IPMT). We report the usefulness of preoperative assessment by magnetic resonance cholangiopancreatography (MRCP) compared with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied 12 cases of surgically resected IPMT in the pancreatic head. The MRCP and ERCP images were interpreted, and we examined the detection rate of each imaging technique for the Wirsung duct, the Santorini duct, the entire cystic tumor, and the communication between the tumor and the ducts. RESULTS: In all cases MRCP correctly identified the entire cystic tumor, and the communication between the tumor and the pancreatic ducts was seen in 64% of cases. In contrast, the detection rate by ERCP of the entire cystic tumor and of the communication between the cystic tumor and the ducts was only 8% and 18%, respectively. CONCLUSION: MRCP clearly showed the relationship of the cystic tumor and the pancreatic ducts and was very useful for preoperative imaging for partial pancreatic head resection.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Cistadenoma Mucinoso/diagnóstico , Imageamento por Ressonância Magnética , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico , Cuidados Pré-Operatórios , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Patients with intraductal papillary mucinous tumor have a favorable prognosis after surgical treatment. When this neoplasm is located in the head of the pancreas, resection has conventionally required pancreatoduodenectomy. Although pancreatoduodenectomy can now be performed with a low mortality rate, morbidity still occurs frequently. METHODS: Between November 1982 and January 1999, 38 intraductal papillary mucinous tumors of the pancreas were resected at the Chiba University Hospital. Seven patients (18%) underwent inferior head resection of the pancreas. In this preliminary study, the operative technique is presented, and its efficacy in improvement of quality of life is evaluated. RESULTS: Patients with intraductal papillary mucinous tumor underwent resection with no perioperative mortality. After discharge from hospital, 6 patients who underwent inferior head resection were still alive without recurrent disease after a median follow-up of 3 years. However, 1 patient developed peritoneal dissemination and died 18 months after inferior head resection. Patients had regained 98% of preoperative weight 1 year after inferior head resection. N-benzoyl-L-tyrosyl-p-amino-benzoic acid (BT-PABA) excretion test showed the same value before (73%) and after (73%) inferior head resection (n = 7). Pancreatic fistulas occurred more frequently after inferior head resection (38%), but the incidence of major complications was similar between inferior head resection and other types of pancreatic head resection. CONCLUSIONS: Pancreatic function was well preserved, and patients regained 98% of preoperative weight after inferior head resection of the pancreas. The authors concluded that the limited involvement of intraductal papillary mucinous tumors enables the surgeons to perform inferior head resection of the pancreas.
Assuntos
Adenocarcinoma Mucinoso/cirurgia , Carcinoma Papilar/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/mortalidade , Adulto , Idoso , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Qualidade de Vida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We report a case of intrahepatic cholangiocarcinoma treated by extended right lobectomy and resection of the inferior vena cava (IVC) and portal vein. A 53-year-old man was referred with elevated serum alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels on April 23, 1999. He was not jaundiced and did not have any symptoms. Endoscopic retrograde cholangiopancreatography (ERCP) revealed irregular strictures in both the anterior and posterior segmental ducts. Contrast-enhanced computed tomography (CT) scan demonstrated a low-density tumor with an unclear margin in the right lobe of the liver. The patient underwent extended right hepatic lobectomy and total caudate lobectomy. Partial resection of the IVC (6 cm) was performed under total hepatic vascular exclusion. The main portal trunk and left portal vein were resected and reconstructed with an end-to-end anastomosis. Macroscopically, a 5.0 x 5.0 x 4.5-cm periductal infiltrating-type tumor occupied the right hepatic parenchyma along the posterior and anterior segmental ducts. Histological examination revealed moderately differentiated tubular adenocarcinoma with marked perineural invasion. Lymph node metastasis was observed in the hepatoduodenal ligament and posterior surface of the pancreatic head. The resected margins of the common bile duct and left hepatic duct were free of tumor. The patient's postoperative course was uneventful, and he was discharged from hospital on the 28th postoperative day. Nine months after the operation, he suddenly developed obstructive jaundice, and died with recurrent disease. This is the first reported case of intrahepatic cholangiocarcinoma treated with major hepatectomy and resection of the IVC and portal vein except ex situ procedure. This aggressive surgical approach may offer hope for patients with intrahepatic cholangiocarcinoma involving the IVC.
Assuntos
Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Veia Cava Inferior/cirurgia , Anastomose Cirúrgica , Colangiocarcinoma/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Veia Porta/patologia , Veia Cava Inferior/patologiaRESUMO
BACKGROUND: An increasing number of intraductal papillary mucinous tumors of the pancreas have been reported in recent years. The indolent character and favorable prognosis of this neoplasm have been described. METHODS: Intraductal papillary mucinous tumors were classified into main duct type (n = 8) and branch type (n = 28) according to the dominant location of the tumor. This single-institute study examined the clinicopathological features and outcome after surgical resection in patients with intraductal papillary mucinous tumors. RESULTS: The gender, age, tumor size, and prognosis were quite similar for the main duct type and branch type groups. Branch type tumors were more frequently located in the head of the pancreas than were main duct type tumors. Histological examination revealed that 88% of main duct type tumors were adenocarcinomas; however, only 46% of branch type tumors were adenocarcinomas. Five-year survival rates for the patients with all main duct type tumors (n = 8), main duct type adenocarcinoma (n = 7), all branch type tumors (n = 28), and branch duct adenocarcinoma (n = 13) were 100%, 100%, 90.6%, and 90.9%, respectively. CONCLUSIONS: Intraductal papillary mucinous tumors had a favorable prognosis after surgical treatment. A curative pancreatectomy should be indicated for this localized malignant tumor.
Assuntos
Cistadenoma Mucinoso/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Cistadenoma Mucinoso/mortalidade , Cistadenoma Mucinoso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Análise de SobrevidaRESUMO
BACKGROUND: A reflux of pancreatic juice into the biliary tract caused by pancreaticobiliary maljunction (PBM) has been considered important in the development of biliary tract carcinogenesis in choledochal cysts. We excised extrahepatic bile ducts in patients with choledochal cysts to terminate the reflux of pancreatic juice. We investigated whether this surgery could stop the development of the residual bile duct carcinoma. METHODS: Fifty-six patients with a diagnosis of PBM with choledochal dilatation underwent surgical excision of extrahepatic bile ducts. We applied a person-year method to compare the relative risks (observed number/expected number) of biliary tract carcinoma before and after surgery. RESULTS: In 3 patients, bile duct carcinoma developed in residual dilated segments 19 years 6 months, 8 years 8 months, and 2 years 5 months, respectively, after surgery. Although the relative risk in the post-surgery group was slightly decreased by surgery, it was still high compared with that of the general population. CONCLUSIONS: The incidence of bile duct carcinoma is still high, even after excision of extrahepatic bile ducts in PBM patients with choledochal dilatation. For these patients, careful long-term follow-up is necessary, especially after operations that leave the dilated bile ducts, such as cases of Todani's type IV-A.
Assuntos
Neoplasias dos Ductos Biliares/prevenção & controle , Ductos Biliares Extra-Hepáticos/anormalidades , Ductos Biliares Extra-Hepáticos/cirurgia , Carcinoma/prevenção & controle , Ductos Pancreáticos/anormalidades , Adolescente , Adulto , Idoso , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/etiologia , Refluxo Biliar/cirurgia , Carcinoma/epidemiologia , Carcinoma/etiologia , Cisto do Colédoco/complicações , Cisto do Colédoco/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The anti-tumor effects of high-energy shock waves (HESW) in combination with cisplatin (CDDP) and ATX-70, as a photosensitizer, were investigated in vitro and in vivo. METHODS: Active oxygen generation by HESW was studied by means of electron spin resonance (ESR) system. The anti-tumor effects of HESW in combination with cisplatin (CDDP) and ATX-70 was investigated in vitro and in vivo. RESULTS: HESW exposure induced singlet oxygen or hydroxyl radical. Adding ATX-70 enhanced the cell damage induced by HESW dose-dependently. Ascorbic acid inhibited the combined effect of HESW and ATX-70. Adding CDDP did not enhanced cell damage by HESW. The combined therapy of HESW, CDDP and ATX-70 showed further inhibition of tumor growth in vivo. CONCLUSIONS: These results indicate that HESW activated ATX-70, and that the anti-tumor effect of HESW and ATX-70 was caused by active oxygen generation. HESW is able to be utilized with any other cancer treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ondas de Choque de Alta Energia/uso terapêutico , Neoplasias Hepáticas Experimentais/terapia , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cisplatino/administração & dosagem , Terapia Combinada , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres , Radical Hidroxila/análise , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Estresse Oxidativo , Oxigênio/análise , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/administração & dosagem , Porfirinas/farmacologia , Espécies Reativas de Oxigênio , Oxigênio Singlete , Células Tumorais Cultivadas/transplanteRESUMO
BACKGROUND/AIMS: In this preliminary study, we investigated the efficacy of combined radiofrequency thermal ablation therapy (RFA) with hepatic arterial infusion chemotherapy (HAI) in the treatment of multiple liver metastases from colorectal cancer. METHODOLOGY: Nine patients with bilobular multiple metastases was treated. The number of nodules was 6.0 +/- 3.9 (range: 2-13), and the size was 2.1 +/- 1.0 cm (range: 0.5-4.8 cm) in diameter. RFA was performed using a RF generator operating at 460 kHz with a 15-gauge, 4-prong custom RF needle. Treatment temperature was kept at 90-110 degrees C for 5 min. 5-Fluorouracil (5-FU) was administered by weekly 750-1250 mg/body/5 h as the regimen of HAI. RESULTS: During a 15.2-month follow-up period, 6 of 9 patients survived more than 1 year. Three of the 6 survived more than 2 years. Serum CEA level in 5 patients dropped from 24.5 +/- 9.5 ng/ml to 10.3 +/- 5.5 ng/ml. Local recurrence was observed in 5 patients and new lesions in 4. Extrahepatic recurrence was observed in 5 patients. There were no serious complications but one HAI-related cerebral thrombosis. CONCLUSIONS: Combined RFA with HAI would be effective and safe. This modality provides a new option for the treatment of multiple liver metastases from colorectal cancer.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Hipertermia Induzida , Infusões Intra-Arteriais , Neoplasias Hepáticas/secundário , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
A 46-yr-old woman was admitted to our hospital with mild epigastric pain. Ultrasonography and computed tomography revealed an extremely thickened gallbladder wall. Endoscopic retrograde cholangiopancreatography demonstrated that the main pancreatic duct joined the nondilated common bile duct at the outer point of the duodenal wall (P-C type of pancreaticobiliary maljunction), and the cystic duct joined the common channel directly. The intraoperative amylase levels of the bile juices both in the common bile duct and the cystic duct were high. A cholecystectomy was performed. The wall of the gallbladder was markedly thick, yellowish, elastic, and soft. Histologically, Rokitansky-Aschoff sinus proliferation, hypertrophy of smooth muscles, and fibrosis were seen. The diagnosis was a generalized type of adenomyomatosis. The pathogenesis of the adenomyomatosis was believed to result from chronic stimulation as a result of pancreatic juice reflux. The etiology of this unusual type of junction was considered to be the result of the combination of pancreaticobiliary maljunction and an anomaly of lower junction of the cystic duct.
Assuntos
Adenomioma/complicações , Ducto Colédoco/anormalidades , Ducto Cístico/anormalidades , Neoplasias da Vesícula Biliar/complicações , Ductos Pancreáticos/anormalidades , Adenomioma/diagnóstico por imagem , Adenomioma/patologia , Amilases/análise , Bile/enzimologia , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Ducto Colédoco/diagnóstico por imagem , Ducto Cístico/diagnóstico por imagem , Feminino , Fibrose , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Humanos , Hipertrofia , Pessoa de Meia-Idade , Músculo Liso/patologia , Ductos Pancreáticos/diagnóstico por imagem , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
The effects of prostaglandin E1 (PGE1) and tyrosine kinase inhibitors on hepatic energy status and protein synthesis in ischemic livers were studied using 31P-magnetic resonance spectroscopy in a rat model. The continuous administration of PGE1 significantly increased the beta-adenosine triphosphate/inorganic phosphate (beta-ATP/Pi) ratio and hepatic protein synthesis rate (HPS) after ischemia-reperfusion injury. Microscopic examination showed that the continuous administration of PGE1 inhibited the development of sinusoidal hemorrhage and edema. Thus, it was concluded that PGE1 has a beneficial effect on ischemia-reperfusion injury in the liver. Pretreatment with tyrosine kinase inhibitor also increased the beta-ATP/Pi ratio; however, when tyrosine kinase inhibitor was injected before ischemia, the HPS became significantly reduced. Based on these data, the protective effect of tyrosine kinase inhibitor is unconvincing.
Assuntos
Alprostadil/farmacologia , Metabolismo Energético/efeitos dos fármacos , Isquemia/metabolismo , Fígado/irrigação sanguínea , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Traumatismo por Reperfusão/metabolismo , Animais , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Radioisótopos de Fósforo , Ratos , Ratos WistarRESUMO
We used computer-based virtual endoscopy techniques as a novel approach to clarify the three-dimensional (3D) surgical anatomy of the pancreas and of mucin-producing pancreatic tumors. Thirteen cases (18 lesions) of mucin-producing pancreatic tumors were investigated by virtual pancreatoscopy. Virtual endoscopic images were generated with virtual endoscopy software application on UNIX workstations. We created surface-rendered virtual endoscopic images derived from a computer reconstruction of the cross-sectional magnetic resonance imaging data. Virtual endoscopy could visualize the surfaces of the pancreatic duct and the bile duct, and also demonstrated all cystic tumors. The surfaces of malignant mucin-producing pancreatic tumors were illustrated as being more irregular than those of benign lesions. The virtual endoscopic technique could demonstrate not only a surface-rendered endoscopic image of the tumors but also a 3D reconstructed image of the pancreas. The relationship to anatomic structures located outside the surfaces is continuously maintained and displayed at the same time. Virtual pancreatoscopy was useful for surgical planning of minimally invasive resection of the pancreas.
Assuntos
Simulação por Computador , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/cirurgia , Adenoma/cirurgia , Adulto , Idoso , Endoscopia do Sistema Digestório , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pâncreas/anatomia & histologia , Ductos Pancreáticos/anatomia & histologia , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , Interface Usuário-ComputadorRESUMO
The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.
Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias Pancreáticas/patologia , Polienos/farmacologia , Animais , DNA de Neoplasias/biossíntese , Farnesiltranstransferase , Genes ras/genética , Humanos , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Mutação Puntual , Alcamidas Poli-Insaturadas , Proteínas Quinases/metabolismo , Células Tumorais CultivadasAssuntos
Biópsia por Agulha/instrumentação , Sobrevivência de Enxerto , Transplante de Fígado/fisiologia , Fígado/metabolismo , Agulhas , Biossíntese de Proteínas , Animais , Biomarcadores , Biópsia por Agulha/métodos , Desenho de Equipamento , Fígado/citologia , Masculino , Preservação de Órgãos , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Traumatismo por ReperfusãoRESUMO
BACKGROUND/AIMS: We have previously reported that the hepatic protein synthesis rate, calculated as the uptake rate of L-[4.5 3H] leucine by the protein fraction during a 10-min incubation of a 16-G needle biopsy specimen of liver tissue, represents a high level of liver function and is therefore useful for evaluating liver function. We investigated the hepatic protein synthesis rate level in a pre-transplant liver to learn if it might predict the outcome in a rat orthotopic liver transplantation model. METHODS: Grafts were stored, liver specimens were obtained using a 21-G Chiba type II skinny needle, and the hepatic protein synthesis rate was calculated. Subsequently, liver transplantation was performed, and the hepatic protein synthesis rate level of revascularized liver, tissue blood flow rate, serum alanine aminotransferase, lactate dehydrogenase, hyaluronic acid, ketone body rate, and 2-week survival were examined. RESULTS: The hepatic protein synthesis rate of pretransplant liver was correlated with parameters of post-transplant liver function: hepatic protein synthesis rate of the revascularized liver (r=0.92, p<0.0001), tissue blood flow rate (r=0.77, p<0.004), serum alanine aminotransferase (r=-0.69, p<0.003), lactate dehydrogenase (r=-0.54, p<0.03), hyaluronic acid (r=-0.86, p<0.0002), and ketone body rate (r=0.57, p<0.02). Pretransplant hepatic protein synthesis rate in survivors was 263.6+/-54.2 nmol/mg protein/10 min, while that in nonsurvivors was significantly lower at 162.0+/-39.0 (p<0.0001). When evaluation was made using a logistic regression model, the accuracy predicted using the value of hepatic protein synthesis rate was 95% (19/20). CONCLUSIONS: These results suggest that measuring the hepatic protein synthesis rate of the grafts with a 21-G Chiba type II skinny needle may be a predictive criterion in the assessment of graft viability.
Assuntos
Isquemia/metabolismo , Fígado/metabolismo , Alanina Transaminase/sangue , Animais , Velocidade do Fluxo Sanguíneo , Temperatura Baixa , Sobrevivência de Enxerto , Ácido Hialurônico/sangue , Corpos Cetônicos/sangue , L-Lactato Desidrogenase/sangue , Fígado/irrigação sanguínea , Testes de Função Hepática , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Valor Preditivo dos Testes , Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Taxa de Sobrevida , Fatores de TempoAssuntos
Diabetes Mellitus Experimental/cirurgia , Sobrevivência de Enxerto , Transplante das Ilhotas Pancreáticas/fisiologia , Transplante de Pâncreas/fisiologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Transplante das Ilhotas Pancreáticas/patologia , Fígado/metabolismo , Masculino , Transplante de Pâncreas/patologia , Biossíntese de Proteínas , Ratos , Ratos Endogâmicos , Transplante IsogênicoRESUMO
We developed a new technique for partial resection of the head of the pancreas with an end-to-side pancreaticoduodenostomy, while preserving the duodenum, the common bile duct, and the upper part of the head of the pancreas around the duct of Santorini. A resection of the inferior head of the pancreas was performed in a patient with an intraductal mucin-producing tumor of the pancreas. This procedure is considered to be appropriate for treating both benign disease and noninvasive malignant disease involving either the uncinate process or the duct of Wirsung, because it removes both the uncinate process and the pancreatic tissue around the duct of Wirsung. We thus believe that a resection of the inferior head of the pancreas with an end-to-side pancreaticoduodenostomy can help play a significant role in the management of patients with benign diseases and localized malignant tumors of the pancreas.