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)

In this study we examined the cytostatic compounds 5 FU and FUDR which are most frequently used in regional chemotherapy for any incidence of hepatobiliary toxicity in animals. For this we compared the intraarterial as well as the intraportal application. Differences between the treatment groups were found in the biliary extraction of these two cytostatic agents. The quantity of metabolites in the bile which could be proven by the MR-spectroscope was highest following intraarterial FUDR infusion, but strong deviations were found in individual cases. A correlation of these findings with the observed frequent hepatobiliary side effects could not be found. It could be shown that the rate and severity of chemical hepatitis and lymphocytic infiltrations in the periportal fields of the liver has no connection to either the cytostatic agent used nor the application form used. Although a sclerosing cholangitis could only be seen in intraarterial therapy. In these cases both cytostatic agents under observation were found to be responsible for this effect in the examined animals. The incidence of sclerosing cholangitis during regional chemotherapy of liver metastases with fluoridised pyrimidines seems to be contingent on multiple factors such as circulation disturbances in combination with drug toxicity.
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PMID:[Animal experiment studies of the toxicity of fluorodeoxyuridine (FUDR) and 5-fluorouracil (FU) within the scope of regional liver infusion chemotherapy]. 213 86

Fifty-nine colorectal cancer patients with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to February 1989 were reviewed. Excisions of metastatic liver cancer were performed in 36 patients and 23 had nonresectable metastatic liver cancer. Catheter troubles, including severe infections (8), extravasations (3), obstruction (1) and other (1) occurred in 13 (22.0%) patients, and 6 patients (10.2%) were unable to receive IAIC. Three patients did not undergo IAIC because of hepatitis or other reasons. Serious complications following IAIC, including sclerosing cholangitis (SC) (6), extravasations (6) and obstructions (3) were observed in 15 patients (30.0%). 5-Flourouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps weekly or every two weeks. Total infused doses of 5-FU ranged from 7,000 to 26,250 mg (mean: 11,800 + 7,700 mg) and those of MMC from 24 to 84 mg (mean: 45.3 + 25.8 mg) in 6 patients (12%) with SC, 4 resectable and 2 non-resectable cases. All six patients with SC had cholangiographic abnormalities of the biliary tract by endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), but serial CT examination of the liver did not show any progression of the tumor at the hilum in these patients. Segmental stricture at the common hepatic duct and bifurcation appeared specific to IA-5-FU induced SC. Obstructive jaundice occurred in 3 patients. Four patients had epigastralgia and 3 exhibited elevated alkaline phosphatase level prior to the cholangiographic examination. The elevated level of alkaline phosphatase was reversible in one patient without obstructive jaundice. Although the relation of the sclerosing process to IA-5-FU dose is not yet clear as well as IA-FUDR, it should be important to make an early detection of SC by ERCP and also to discontinue IAIC as soon as possible. In our opinion, SC may relate to the arterial delivery of 5-FU. In order to prevent SC, devascularization of the right hepatic artery via surgical procedures may well be effective, because retrograde flow from the right hepatic artery was confirmed by several clinical and anatomical studies.
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PMID:[Complications of intra-arterial infusion chemotherapy in patients with colorectal cancer with liver metastasis, with special reference to IA-5-FU induced sclerosing cholangitis]. 250 36

Twenty evaluable patients with primary or secondary neoplastic liver involvement received FUDR (0.2 to 0.3 mg/kg per day) by continuous infusion to the hepatic artery for 14 days, every 4 weeks, through a surgically implanted Infusaid (USA) pump. In addition to FUDR, MMC (15 mg/m2 every 6 to 8 weeks) was given to 14 patients with colorectal cancer and one patient with breast cancer, and ADR, (40 mg/m2 every 4 to 6 weeks) was given to 5 patients with hepatocellular carcinoma. MMC and ADR were given as a bolus injection, through the pump sideport. Radiation therapy to the liver (2,000 rads in fractions of 180 to 200 rads each) was given to eight patients with colorectal carcinoma. In total, the 20 patients received 218 months of treatment and 580 injections. The overall remission rate (complete, partial and minor response) was 55%; one patient with a colorectal carcinoma achieved a CR and seven patients (35%) a PR; three patients (15%) had a MR, and in eight patients (40%) stabilization of disease was observed. Overall median survival was 12 months: 15.5 months for colorectal cancer patients and 7.5 months for patients with hepatocellular carcinoma. Toxicity consisted mainly of chemical hepatitis, mild to severe peptic disease and sclerosing cholangitis. Hematological toxicity was not observed. These data suggest that chemotherapy through the hepatic artery, while still experimental, may be considered for selected patients with tumor confined to the liver.
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PMID:Treatment of primary and metastatic liver cancer using an implantable chemoinfusion pump. 284 96

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

Fifty-one patients with metastatic colorectal carcinoma confined to the liver received intraarterial chemotherapy through the hepatic artery via a subcutaneous pump. The chemotherapy consisted of sequential 14-day infusions of floxuridine (FUDR) and dichloromethotrexate (DCMTX) or a 14-day infusion of FUDR and bolus mitomycin (MMC). Twenty-four patients (47%) developed hepatitis with an elevation of hepatic serum transaminase (serum glutamic oxaloacetic transaminase, SGOT, or serum glutamic-pyruvic transaminase, SGPT). The median time to develop hepatitis was 11 weeks after initiation of chemotherapy. The morphologic effects of chemotherapy were evaluated in eight patients with hepatitis. All the patients with hepatitis had normalization of the serum transaminases after temporary cessation of chemotherapy. There was a trend toward a greater chance of remission in patients who developed hepatitis. Sixty-seven percent of the patients with a therapeutic response had hepatitis, whereas only 33% of the patients without a response had hepatitis. However, this difference was not statistically significant. The occurrence of hepatitis was not related to FUDR dose, drug program (FUDR-DCMTX vs. FUDR-MMC), pump flow rate, hepatic arterial anatomy, sex, or age of the patients.
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PMID:Hepatitis in patients receiving intraarterial chemotherapy for metastatic colorectal carcinoma. 295 Jul 52

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.
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PMID:Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump. 315 93

Brachytherapy by embolization with radiotherapeutic microspheres following intraarterial infusion of a radiosensitizer represents an attempt to combine several selective modalities into a more potent, focused attack on regionally confined tumors. In pursuit of this goal, we examined the ability of foxhounds with surgically implanted hepatic arterial (HA) delivery systems to tolerate a clinically relevant dosage of HA yttrium-90 (Y-90) by microsphere administration either alone or preceded by a 28-day constant HA infusion of either 5-bromo-2'-deoxyuridine (BUDR) or a control solution. Five dogs received BUDR (10 mg/kg/day) and five a control buffer infusion for 28 days immediately prior to the administration of Y-90-coated 15 micron resin microspheres (equivalent of 5000 rads to the entire liver) to each dog on day 31. In all animals, blood counts, bilirubin, amylase, appetite, weight, and behavior remained unchanged. Dogs receiving the microspheres after buffer infusion alone exhibited no hepatic enzyme alanine aminotransferase or alkaline phosphatase elevation. Alanine aminotransferase and alkaline phosphatase levels both rose during the third week of BUDR infusion, and while subsequent microsphere administration further increased enzyme levels, these levels had largely normalized by necropsy on day 82. At necropsy, the type and degree of hepatic toxicity among the animals receiving radioactive microspheres was comparable to that previously described in patients receiving external beam hepatic irradiation at conventional doses (2000-3000 rads). Also noted was a radiation-induced cholecystitis (due in large part to the gallbladder's total reliance on the hepatic artery for blood supply). One resin microsphere dog exhibited a small quantity of microspheres in the lungs causing focal radiation-induced granulomas suggesting the need to assess shunting of microspheres through the liver in clinical studies. Thus, HA Y-90 microspheres with BUDR can produce acceptable, nonlethal, and tolerable toxicities in this dog model suggesting that clinical studies of this combination are not likely to be contraindicated by synergistic toxicity. Although HA BUDR did not contribute significantly to the toxicity of the Y-90 microspheres, HA BUDR by itself administered uninterrupted for 4 weeks may, like HA FUDR (clinically), cause chemical hepatitis/cholangitis. The unexpected fragmentation of the resin spheres (albeit without myelosuppression) has led us to begin studies with a recently developed nondisruptible glass microsphere (ThereSphere) in which the Y-90 is part of the glass matrix and cannot leach.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs. 358 Oct 69

Natural history of patients with colorectal liver metastases is not significantly changed even by curative resection. The majority unfortunately relapse. The results of adjuvant treatment after resection were evaluated by analysis of 17 publications as well as by own data (60 patients). 340 patients were either treated by intraarterial (n = 201), systemic (n = 82), intraportal (n = 29) or intraperitoneal (n = 28) chemoinfusion (5-Fluorouracil or Floxuridine). An alternative approach was the treatment with specific immunotherapy using tumor vaccination (n = 35) or monoclonal antibodies (n = 20). Morbidity of adjuvant treatment includes local (chemical hepatitis, biliary sclerosis) and systemic (diarrhea, stomatitis) side effects. Technical complications could reach a level of up to 50% in case of local administration. With exception of 6 studies no comparison with a resection only group was performed. Despite postulated increase of survival and recurrence free time with historical controls the results of current ongoing studies are needed before general use of adjuvant treatment can be recommended.
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PMID:[Results of resection and adjuvant therapy of liver metastases of primary colorectal tumors--a review of the literature]. 750 91

Although hepatic arterial infusion (HAI) chemotherapy using fluoropyrimidines is pharmacologically regarded as an ideal therapy for colorectal liver metastases, clinical evaluation of prophylactic HAI following curative hepatectomy has not been carried out. In this report, we review the published literature on this treatment and discuss its efficacy and adverse effects. Fluorodeoxyuridine (FUDR) or 5-fluorouracil (5-FU) was used as the agent and a total dosage of 10-20 g was administered for 6-12 months in most studies. Despite adjuvant therapy, complications including hepatitis, cholangitis, peptic ulcer, and obstruction of the hepatic artery are often reported. Cessation of therapy was also necessary in some studies because of adverse effects or technical problems. In terms of therapeutic effect, significantly higher disease-free survival was achieved in most studies. However, it is still controversial whether this treatment has an ultimate survival benefit. Thus reasonable protocols that do not impair patients' quality of life should be adopted for prophylactic HAI. Furthermore, it is desirable to develop a new regimen combining HAI with systemic chemotherapy to achieve improved survival rates.
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PMID:[The role of prophylactic hepatic arterial infusion chemotherapy after potentially curative resection of hepatic metastases from colorectal cancer]. 1097 44