RESUMEN
AIM: This randomized phase III trial compared hepatic arterial infusion (HAI) chemotherapy with 5-fluorouracil (5-FU) followed by uracil/tegafur (UFT) and leucovorin (LV) versus UFT/LV alone for patients with curatively resected liver metastases from colorectal cancer (CRC). METHODS: The study was designed to include 280 patients to be randomized to receive either HAI with 5-FU followed by UFT/LV (Arm A) or UFT/LV alone (Arm B) to assess whether HAI chemotherapy improved disease-free survival (DFS). RESULTS: Forty-four patients were randomized. Three-year DFS was relatively worse in the experimental arm although this difference was not statistically significant (43.5% in Arm A vs. 58% in Arm B; hazard ratio [HR], 1.304; P = 0.534). The experimental arm also tended to have a worse 3-year overall survival rate (80.2% in Arm A vs. 85.2% in Arm B; HR, 2.255; P = 0.192). There was no significant difference in the frequency of Grade 3 or higher toxicities between the two arms. CONCLUSION: Although this study was limited by a small sample size after early study termination, our analysis found that HAI with 5-FU followed by UFT/LV did not improve the DFS of patients with curatively resected liver metastases from CRC compared with UFT/LV alone. The future studies are necessary to evaluate the survival benefit of HAI in combination with newer systemic chemotherapeutic agents for patients with resectable liver metastases from CRC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Arteria Hepática , Humanos , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tegafur/administración & dosificación , Tegafur/efectos adversosRESUMEN
BACKGROUND: The feasibility and efficacy of adjuvant hepatic arterial infusion (HAI) in preventing the development of liver metastases in patients with advanced colon carcinoma have not been validated. The aim of this randomized controlled study was to compare the feasibility of HAI and the protective effect against liver metastasis after curative resection to those of systemic chemotherapy. METHODS: Between July 2000 and June 2003, 91 patients were enrolled. Patients were randomly assigned to receive 5-fluorouracil (5-FU) via continuous venous infusion (CVI) or intra-hepatic arterial weekly high-dose 5-FU (WHF). The primary endpoint was overall survival (OS). RESULTS: In the WHF group, the cumulative failure rate of hepatic arterial catheterization was 16.7% at 6 months. The occurrence of grade 3 adverse events was comparable between the groups. The 5-year OS rates were 59.0% in the CVI group and 34.9% in the WHF group (P = 0.164). CVI tended to show a protective effect against liver metastasis regarding the 5-year liver-specific cumulative recurrence rate: CVI, 45.0% vs. WHF, 68.3%; P = 0.037). CONCLUSION: HAI therapy has a certain protective effect against liver metastasis after curative resection in patients with colorectal cancer. However, this therapy did not contribute to any marked improvement in their overall survival.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Infusiones Intraarteriales/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Quimioterapia , Femenino , Arteria Hepática/efectos de los fármacos , Humanos , Infusiones Intraarteriales/efectos adversos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana EdadRESUMEN
CASE 1: A 30-year-old male with a loss of appetite and hematemesis was diagnosed with scirrhous gastric cancer upon detailed examination. Laparoscopic biopsy showed it to be Group V. Pre-operative diagnosis was T3N3P1HOM1, Stage V. Three courses of pre-operative chemotherapy (NAC) of TS-1+CDDP were performed. Laparoscopic examination as well as imaging showed a clear reduction in tumor size. Total gastrectomy, resection of the small intestine and cholecystectomy were performed. Pathological findings were type 4, por 2, pT3 (ss), ly1, v0, pN0, pM1 (gall bladder, small intestine): pStage IV. CASE 2: A 55-year-old male with epigastric pain was diagnosed with scirrhous gastric cancer upon detailed examination. Pre-operative diagnosis was T3N1P1H0M0, Stage IIIA. Upon surgery, gastro-jejunal anastomosis was performed as resection was not an optional. Three courses of TS-1+CDDP were performed. A clear reduction of tumor size was noted upon laparoscopic examination as well as imaging and distal gastrectomy was performed. The pathological findings shown were type 4, por 2, pT3 (ss), ly2, v1, pN1, p1, pStage IV. The prognosis for inoperable gastric cancer is not promising and there is no established treatment guideline, however, there are cases in which TS-1+CDDP therapy has made surgery possible, and with the anticipation of extended survival, can be considered a useful therapy method.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anastomosis Quirúrgica , Colecistectomía , Cisplatino/administración & dosificación , Gastrectomía , Humanos , Intestino Delgado/cirugía , Yeyuno/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estómago/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tegafur/administración & dosificaciónRESUMEN
We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.
Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Ablación por Catéter , Terapia Combinada , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intraarteriales , Leucovorina/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tomografía Computarizada por Rayos XRESUMEN
We studied one case in which the application of RFA was used for colorectal liver metastases with cirrhosis. The patient was a 51-year-old male. Sigmoid colon cancer and hepatocellular cancer (S5, S6, S8) were diagnosed before surgery. RFA was planned, as resection was determined to be impossible, because of reduced reserve liver function due to hepatitis B and cirrhosis. Resection of the Sigmoid colon was performed. Rapid pathological diagnosis was performed on the liver tumor and it was determined to be metastases from the sigmoid colon cancer. RFA was performed on the liver tumor with the expectation of local control. After the operation, WHF arterial infusion was performed as an outpatient, but the blood platelet count decreased and that resulted in impaired liver function making the continuation of WHF arterial infusion at a regular pace difficult. After 11 months from the operation, multiple recurrences appeared and the infusion was restarted. Consequently, the tumor size was reduced. Following the infusion, however, the liver function became impaired and there was no choice but to discontinue the infusion. After one year and 9 months from the operation, multiple recurrences appeared in the residual liver and WHF arterial infusion was restarted. The tumor size gradually reduced after the infusion and only S3 currently remains with good local control. Because this example was a case with multiple metastases along with a high level of liver function impairment, RFA was tested and good local control was achieved. In cases such as these where liver resection is not possible, local ablation therapies including RFA are applicable.
Asunto(s)
Ablación por Catéter , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Fluorouracilo/administración & dosificación , Hepatitis B/complicaciones , Humanos , Infusiones Intraarteriales , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias del Colon Sigmoide/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, epirubicin, MMC) therapy. SUBJECTS: Data for 111 patients with liver metastasis from gastric cancer were collected from January 1977, until June 2003 (synchronous: 74 cases, asynchronous: 37 cases). Thirty patients were H1, 20 were H2 and 61 were classified as H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 10), Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intraarterial infusion (5 cases). Group B: Resection of the primary lesion (n = 67), Group B1: Resection of the primary lesion only (46 cases), Group B2: Intraarterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (4 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: 1-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%. 4.8 months; and Group C: 6%, 3.9 months, respectively. One case from Group A2a and 2 cases from Group B2a have survived for 3 years or longer. CONCLUSION: 1) We treated 3 patients with liver metastasis from gastric cancer who survived for 3 years or longer. 2) Resection of the primary lesion along with hepatic intraarterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended length of survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Gástricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Gastrectomía , Hepatectomía , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
BACKGROUND: The treatment of refractory ascites remains a challenge in cirrhosis with ascites and end-stage renal disease (ESRD). Successful experiences with continuous ambulatory peritoneal dialysis (CAPD) for treatment of ESRD patients with ascites secondary to liver cirrhosis have been reported, but the CAPD modality has the drawback of protein loss and was observed to cause patients to become severely malnourished. We devised a CAPD method for treatment of ascites without protein loss. We use a peritoneal dialysis (PD) system to drain ascitic fluid and to reinject concentrated ascites into the abdomen after extracorporeal ultrafiltration of the ascitic fluid using a hemodialysis dialyzer and pump. Here, we report our experience with 2 cirrhotic patients with ascites treated by this method. PATIENTS AND METHOD: Ascites are collected by gravity through a Y transfer set into a 3-L plastic bag for intravenous hyperalimentation. The ascitic fluid drained is removed by a pump at a rate of 200 mL/min (AK-90: Gambro Lundia, Lund, Sweden) and passed through a hollow-fiber dialyzer with triacetate membrane (FB-210G: Nipro, Osaka, Japan). Heparin (5,000 U) is infused into the inflow line at the start of the session only. At the end of treatment, about 500 mL concentrated ascitic fluid is returned to the peritoneal cavity by gravity through the Y transfer set. Case 1: A 77-year-old female was referred to us because of massive ascites from hepatic cirrhosis associated with hepatitis B infection and renal insufficiency. Abdominal paracentesis was required once weekly for recurrence of massive ascites. As a result, the patient was obliged to stay in the bed almost all day, and her nutritional condition deteriorated because of poor appetite and respiratory compromise. Using the Y transfer set, we commenced using our method, and performed it thrice or twice weekly. After 9 months of treatment, the patient's body weight was being maintained at 52 kg, and her serum albumin level had risen from 2.4 g/dL to 3.4 g/dL without albumin administration. Case 2: A 61-year-old male with diabetes from the age of 51 was diagnosed with hepatitis C at age 53. At age 60, his renal function deteriorated, requiring hemodialysis (HD). After 3 months, abdominal distention was noted, and HD was frequently complicated by low blood pressure, large weight gains between HD treatments, and interruption of HD sessions. Albumin administration was required to treat the low blood pressure. Ascites was poorly controlled using HD, and tense ascites developed, requiring repeated paracentesis for comfort. At first during application of our method, ascitic fluid volume was 6 L per thrice-weekly HD session. After 5 months, ascitic fluid volume had diminished to about 2 - 3 L per HD session, and we decreased the frequency of our method to once weekly. Protein levels in the ascitic fluid were 6 g/dL at the start of treatment and decreased to 2 - 3 g/dL after 6 months. Hemodynamic instability during HD was reduced. CONCLUSION: We conclude that management of refractory ascites by using a PD system with extracorporeal ultrafiltration by an HD dialyzer is useful. The technique compensates for the drawbacks of PD management of ESRD patients with ascites, although further experience with the technique is necessary.
Asunto(s)
Ascitis/terapia , Hemodiafiltración , Diálisis Peritoneal , Anciano , Femenino , Hemodiafiltración/instrumentación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy. SUBJECTS: One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer. CONCLUSION: 1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Epirrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Mitomicina/administración & dosificación , Neoplasias Gástricas/patología , Hepatectomía , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Tasa de SupervivenciaRESUMEN
Of 66 examples of hepatic metastases from colorectal cancer, 30 cases in which resection was performed had 3- and 5-year cumulative survival rates of 66.7% and 56.8%, while in 36 cases in which resection was not possible, the percentages were 8.7% and 2.9%, respectively. In two of the latter cases, resection was possible following WHF (5-FU 1,000 mg/m2 5 h qw). Case 1: A 58-year-old male, with rectal cancer and multiple metastases (H3, synchronous). Arterial infusion was performed 21 times, with the total volume of 5-FU administered being 31.5 g. The size of the lesions was reduced and hepatic resection was performed. The patient later died due to local recurrence and intra-abdominal lymph node metastases. He had survived 2 years and 11 months following hepatic resection and was free from recurrence of hepatic metastases. Case 2: An 82-year-old female, with cancer of the ascending colon, sigmoidal colon and multiple hepatic metastases (H3, metachronous). Arterial infusion was performed 16 times, with the total amount of 5-FU administered being 20 g. A lowering of CEA levels and reduction of tumor size were achieved, and hepatic resection was performed. Seven months following hepatic resection, CEA levels are normal and no distant metastases or recurrence in the residual liver have been found: possibly a complete cure. Even among cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible following hepatic arterial infusion chemotherapy, with the possibility of complete cure.