Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.
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PMID:Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR. 294 Nov 40

Jaundice develops in many patients with liver metastases from colorectal adenocarcinoma during hepatic arterial infusion chemotherapy (HAIC). The usual cause is thought to be hepatotoxicity from the chemotherapeutic agent or biliary obstruction from progressive neoplastic disease. The authors evaluated the abdominal computed tomography and ultrasound examinations performed on 49 patients who were jaundiced during long-term HAIC. In only one patient was diffuse intrahepatic biliary dilatation caused by an obstructing mass in the porta. Two patients had metastatic hepatic lesions causing focal biliary obstruction. Intrahepatic dilatation without an obstructing mass occurred in 20 patients. Percutaneous or endoscopic cholangiograms were commonly interpreted prospectively as showing extrinsic compression by metastases, but no mass was confirmed on imaging studies. Seven patients had focal intrahepatic ductal dilatation from stricture without an associated mass. The remaining 19 patients had normal-caliber ducts; their jaundice was caused by chemical hepatitis. This series suggests that the most common causes of jaundice in these patients are chemical hepatitis and common bile duct stricture, complications of intraarterial chemotherapy, rather than neoplastic obstruction. Stricture formation may be confused with extrinsic compression on direct cholangiograms.
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PMID:Causes of jaundice during hepatic artery infusion chemotherapy. 294 26

Twenty patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant perioperative therapy that included hepatic arterial mitomycin C and floxuridine (FUDR). The median survival for all 20 patients was 51 months: 10 are still alive with a median postoperative follow-up of 49 months; 6 are disease-free with a median postoperative follow-up of 43 months. Among 10 patients in whom the surgical margins of the specimen contained tumor cells, the median survival was 52 months. This survival was comparable to that among 10 patients in whom the surgical margins were tumor free (P = 0.22). Neither the number of metastatic liver deposits nor the disease-free interval between the primary diagnosis of colorectal carcinoma and the development of liver metastases significantly affected survival. A transient chemical hepatitis which resolved before the next scheduled treatment was associated with 50% of arterial chemotherapy cycles (approximately 70% of the patients). Gastric or duodenal ulcerations occurred in 23% of the patients. Surgical complications were either pulmonary such as pleural effusion or atelectasis, or wound infections and subphrenic abscesses. Although these results compare favorably with the results in previously published series, this aggressive adjuvant chemotherapy appears to be particularly justified in patients with tumor positive surgical margins or those with multiple tumor masses and, therefore, are characterized by a poor prognosis.
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PMID:Adjuvant perioperative hepatic arterial mitomycin C and floxuridine combined with surgical resection of metastatic colorectal cancer in the liver. 294 22

Sixty-four patients were entered into a randomized trial that evaluated intra-arterial (I.A.) versus intravenous (I.V.) 5-fluorodeoxyuridine (FUDR) for colorectal liver metastases. There was a significant improved response rate for I.A. (62%) compared with I.V. (17%) treatment (p less than 0.003). However, the improved response rate for patients in whom I.A. therapy was used did not translate to a significantly improved survival rate. The 2-year actuarial survival rates for the groups for which I.A. and I.V. therapy was used were 22% and 15% respectively, with the survival curves not differing significantly (p = 0.27). These results may have been due to the inclusion of patients with tumor in draining hepatic lymph nodes. The presence of tumor in hepatic lymph nodes was associated with a poorer prognosis. Analysis of a subgroup of patients with negative hepatic lymph nodes suggested an improved actuarial survival rate in patients for whom I.A. versus I.V. therapy was used (p less than 0.03). The toxicity of I.A. FUDR was considerable, and side effects included chemical hepatitis (79%), biliary sclerosis (21%), peptic ulcers (17%), and gastritis/duodenitis (21%). The only major effect of toxicity of I.V. FUDR was severe diarrhea (59%). Regional I.A. FUDR allowed more drug delivery to liver tumors, which resulted in increased tumor responses when compared with use of systemic therapy. However, the small gain in survival seen in a select subgroup of patients with negative hepatic nodes appeared to be offset by the toxicity of I.A. FUDR.
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PMID:A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. 296 14

Technetium-99m galactosyl-neoglycoalbumin ( [Tc]NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis (two had concurrent hepatoma and one chronic active hepatitis), and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and [Tc]sulfur colloid scintigraphy. Kinetic modeling of dynamic [Tc]NGA data produced estimates of standardized hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, [HBP]. Clinical correlation was by classical Child-Turcotte criteria (CTC). Significant rank correlation was obtained between [HBP] estimates and CTC scores (rs = -0.72, p = 0.001). This correlation supports the hypothesis that [HBP] is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced [HBP] may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.
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PMID:Technetium-99m NGA functional hepatic imaging: preliminary clinical experience. 299 17

If liver metastases are diffuse and spread out in the two lobes of the liver, the question remains as to which treatment should be given. Experimental studies showed that when a tumor grows, its vascular pattern becomes mainly arterial. However, if the tumor is still increasing, its center becomes progressively necrotic. After hepatic artery ligation the blood flow of the liver metastases decreases by 90% in the tumor but depriving the arterial circulation of the tumor is not sufficient to achieve a complete cure since the portal blood supply always saves a rim of neoplastic cells around the necrotic area. On the other hand, local infusion of chemotherapy for liver metastases by the arterial route showed a response rate varying between 34 and 70% and the median survival varying between 8 and 17 months. When FUdR chemotherapy was administered using a totally implantable drug infusion pump no improvement in the survival was observed and moreover a high level of toxicity was described including hepatitis and biliary sclerosis. A combined therapy seems a rational approach to treat tumor cells in surviving to the arterial ligation by perfusing the liver with cytotoxic drugs via the portal vein. Taylor's study was very promising but a randomized phase III clinical trial led by the gastrointestinal cancer group of the EORTC with the aim to evaluate the effectiveness of hepatic artery ligation and portal infusion of 5-FU did not show any difference in the survival of the treated patients when compared with patients treated by hepatic artery ligation alone. 77 patients were registered. Data are now available for 55 patients, respectively 30 and 25 patients in the treated group and in the control group. In both groups the median time to progression was 6 months and the median survival time was 12 months. 20% of the patients treated by hepatic artery ligation and portal chemotherapy had a response, one of them with a complete response, 5 with partial response and 14 patients without significant change in the size of their metastases. On the contrary, in the group treated by hepatic artery ligation alone, only one patient had a partial response with 13 patients having no change in the size of their metastases.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hepatic artery ligation or embolization and locoregional chemotherapy of liver metastases from colorectal cancer. 313 73

Because of the high rate of response in colorectal liver metastases, intra-arterial chemotherapy was studied in 14 patients with isolated breast cancer liver metastases. After extrahepatic metastasization had been ruled out, a catheter was placed surgically and connected to a cytostatic pump (in two cases) or to a subcutaneous infusion chamber (in 12 cases). Every four to six weeks, the patients with an infusion chamber received a modified FAM treatment (fluorouracil, doxorubicin, mitomycin C) for three days continuously. In 11 out of 14 patients (79%) a clear tumor reduction was observed (duration of remission 11 months). In an average of six cycles of chemotherapy administered, a total of 50% of the patients manifested local side effects (including two cases of toxic hepatitis, one case of biliary sclerosis). Systemic side effects were negligible. Termination of therapy was necessitated by three catheter tip migrations and two thromboses of the hepatic artery. Extrahepatic metastases occurred in six patients. Here, the average latency period between diagnosis of the primary tumor and that of liver metastasis was significantly shorter (x = 9 months) than in the other patients (x = 39 months). Intra-arterial chemotherapy thus represents a therapeutic method which, although complicated, is extremely effective in selected patients with isolated breast cancer liver metastases. A final evaluation must be subject to a randomized comparison with a systemic therapy.
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PMID:[Regional therapy of isolated liver metastases from breast cancer]. 313 53

A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high-performance liquid chromatography with a gel filtration column.
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PMID:Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside). 334 24

Ultrasonically guided fine needle aspiration biopsy is known to be of great value in the diagnosis of malignant liver disease, with an overall accuracy rate of 73-94 p. 100. However, investigators have essentially reported cases of liver metastases. In this report, we examined the diagnostic value of this method in the specific case of tumors associated with cirrhosis. Twenty-seven patients with cirrhosis (20 alcoholic, 4 post-hepatitis, 3 hemochromatosis) with ultrasonically suspected hepatic malignancy were studied. They all presented severe blood clotting disturbances and/or ascites. At the end of the study, all patients had proven malignancy (by post mortem biopsy in 14 cases and/or serum AFP greater than 500 microgram/l in 17 cases). There were 25 primary and 2 metastatic tumors. Twenty-nine fine needle aspiration biopsies were performed under ultrasonic guidance. material suitable for cytologic evaluation was obtained in 25 patients. In 14 cases, a diagnosis of malignant involvement of the liver was firmly established by cytological examination; it was suggested in 4 other cases. Tumor typing was possible in 12 primary and 2 metastatic tumors, in agreement with the proven diagnosis. The present study shows that fine needle aspiration biopsy under ultrasound guidance is a safe and accurate diagnostic procedure in malignant liver disease associated with cirrhosis.
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PMID:[Value of ultrasound-guided cytopuncture in the diagnosis of tumors in cirrhosis. Study of 29 cases]. 397 26

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.
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PMID:Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump. 619 74


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