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

Liver biopsy samples from 110 patients with various liver diseases were stained by orcein according to the method of Shikata et al. Orcein-positive hepatocellular material was observed in only the 31.7% of HBsAg seropositive cases. A positive orcein reaction was frequently found in protracted and chronic viral hepatitis and occasionally in other liver diseases, such as alcoholic and cholestatic hepatitis, as well as in cryptogenetic cirrhosis and in liver metastases. The results obtained suggest a more cautious evaluation of the diagnostic and prognostic significance of orcein-positive hepatocellular material.
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PMID:Orcein-positive material in hepatocytes in viral hepatitis and other liver diseases. 9 49

On the second place in malignant diseases of children, after the leukemias, we could find the Wilms-Tumor. Of the 16 children we treated in the years from 1965 to 1977, 8 children died, 2 patients couldn't be any longer observed and 6 patients are still alive. 5 children of these have obtained now a relapse-free survival from 1 year and 2 months to 2 years and 7 months. We could see, that the prognosis depends only on the stage of the tumor and not on the age of patients. On 3 cases we will try to show, how difficult the diagnosis of the Wilms-Tumor is and how important it is, to treat resolutely pulmonary and liver metastases. As diagnostic methods were used i. v. P., the sonography and the selective renalangiography. Since 1976 our treatment consists of preoperative irradiation of tumors, nephrectomy, postoperative irradiation of tumor-bed and adjuvant chemotherapy (actinomycin D, vincristine and adriamycin). Pulmonary and liver metastases are a domain for chemotherapy, combined with irradiation (danger of pneumonitis and toxic hepatitis) and eventually a resection is necessary. Only the good cooperation of an oncologic team could achieve an improvement of the cure rate of this tumor, as we know from the American countries (survival 75%).
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PMID:[Diagnosis and therapy of Wilms' tumor based on a survey of 16 children with nephroblastoma]. 21 65

Hepatic regional treatment represents an attempt to improve tumor response by increasing drug concentration with low systemic toxicities. Recently in vitro and clinical studies have shown that the cytotoxicity of 5-fluorodeoxyuridine (FUDR) and 5-fluorouracil (5FU) can be potentiated by high doses of leucovorin (LCV). Two pilot studies with intraarterial FUDR, 5FU, and LCV were initiated. Since 1982, 221 patients with colorectal liver metastases were treated by various forms of long-term monthly continuous regional treatment using implantable ports or pumps. FUDR (0.05 to 1.7 mg/kg/d) was administered alone or combined with 5-FU and leucovorin. In 61 patients curative liver resection was possible and was followed by adjuvant arterial treatment. Overall median survival time (MST) was 15 months and increased to 36 months after liver resection. This was influenced by the following important factors: treatment, number of metastases, extent of infiltration, tumor volume, and minimal intraoperatively diagnosed extrahepatic disease. The response rate varied from 69% to 23%. Time of development of extrahepatic progression was not delayed by additional systemic treatment. Local side effects significantly depended on the duration of arterial infusion. The rate of biliary sclerosis ranged from 19% to 0%. Occurrence of chemical hepatitis was between 7% and 38%. In contrast, after combined intraarterial treatment with LCV, systemic side effects, mainly stomatitis and diarrhea, were dose limiting. Despite the improvement of survival after regional treatment, further randomized trials are mandatory to compare regional with relevant systemic treatment.
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PMID:Continuous regional treatment with fluoropyrimidines for metastases from colorectal carcinomas: influence of modulation with leucovorin. 153 72

In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas. A conventional iron oxide preparation not directed at ASG receptors failed to demonstrate specific uptake in these tissues. Attachment of the ASG receptor-directed agents was competitively blocked with a receptor agonist (D(+)-galactose) in these tissues. No attachment of conventional or receptor agents was seen in areas of hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. The studies indicate that in vitro receptor assays are useful in predicting the affinity of new receptor-directed MR imaging contrast agents in human tissue prior to clinical trials.
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PMID:Receptor-directed contrast agents for MR imaging: preclinical evaluation with affinity assays. 173 82

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

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.
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PMID:Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. 229 52

Thirty-three patients with liver metastases of colorectal cancer were treated by intra-arterial 5-FU chemotherapy. The median survival time of all patients was 14 months. A partial remission could be observed in nine patients, and a further 15 patients had stable disease. Patients were treated on an outpatient basis and the toxicity of treatment was mild. We observed no case of sclerosing cholangitis or chemical hepatitis. Intra-arterial 5-FU chemotherapy provided treatment results similar to those reported for FUdR but with less hepatobiliary toxicity.
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PMID:Hepatic arterial infusion (HAI) chemotherapy for liver metastases of colorectal cancer using 5-FU. 232 13

The liver represents the most common site of visceral metastasis for primary gastrointestinal neoplasms, but it is also a common site of metastasis for extra-abdominal tumours including breast cancer, lung cancer as well as other cancers. Metastatic liver disease is often the cause of death for cancer patients. Metastatic liver disease is a heterogenous entity depending upon histologic type, site of primary tumour and other extrahepatic involvement. Surgical resection is feasible only in highly selected patients with no extrahepatic metastasis. The nonsurgical modalities of management of liver metastases include radiotherapy, chemotherapy, biologicals or a combination of these modalities. Hepatic irradiation can produce satisfactory palliation but has dose limiting toxicity of radiation hepatitis. The systemic chemotherapy of liver metastases has evolved over the past decades from single agent systemic treatment to regional infusion chemotherapy. The drugs employed in treatment depend on the site of primary tumour. 5-fluorouracil remains the mainstay of chemotherapy in most gastrointestinal cancers. Recent technological advances in drug delivery system and genetic engineering have given new vistas to nonsurgical management of liver metastases. Ambulatory or implantable pumps have enabled drugs to be delivered by continuous infusion via an implantable vascular access system. Monoclonal antibodies conjugated to toxins or radioisotopes offer exciting prospects for targeted therapy.
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PMID:Non-surgical management of liver metastases. 246 78

Sixty-four patients with a biopsy diagnosis of colorectal cancer with liver metastases were treated with 5-fluorodeoxyuridine (FUDR) infusions. In a pilot study, the first 20 patients were given hepatic artery infusions of FUDR by implanted pumps. The remaining 44 patients were then randomized prospectively to compare the effectiveness of continuous hepatic artery and intravenous infusion of FUDR (IA/IV group; 21 patients) with hepatic artery infusion alone (IA group; 23 patients). A continuous 14-day infusion regimen of FUDR was applied each month. The dosage was 0.2 mg/kg/d of FUDR for the IA group and 0.3 mg/kg/d for the IA/IV group. The complete and partial response rates were each 50% in the pilot study and 52% and 48% in the IA and IA/IV randomized groups, respectively. Drug toxicities in the 64 patients included gastroenteritis (21%), chemical hepatitis (57%), and biliary sclerosis (25%). There was no difference in the toxicity of FUDR in the two randomized groups (P greater than 0.1). Extrahepatic spread of cancer during therapy was found in 61% (n = 14) of the IA group and 33% (n = 7) of the IA/IV group. There was no difference in survival between the randomized groups. The 64 patients were categorized into the following two groups according to their response to therapy: (1) responders (patients with complete or partial remission [n = 32]) or nonresponders (patients with stable disease or progression of metastases [n = 32]). The median survival time was 31 months for responders and 16 months for nonresponders (P less than 0.0001). Intraarterial FUDR infusion provided control of liver metastases. The combination of intraarterial and intravenous therapy seemed to prevent extrahepatic spread during therapy in most of the patients. Survival appeared to be significantly prolonged in patients with a regression of metastases.
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PMID:Regional chemotherapy for hepatic metastases of colorectal carcinoma (continuous intraarterial versus continuous intraarterial/intravenous therapy). Results of a controlled clinical trial. 252 15

The development of safe arterial access devices and totally implantable or portable infusion pumps for intrahepatic chemotherapy has generated a renewed interest in regional treatment of liver metastases from colo-rectal primaries. Several phase II trials have been carried out, mostly using prolonged infusion of fluorinated pyrimidines showing very high activity for this method of treatment with response rates up to 80%. Randomized trials between systemic and regional therapy have confirmed the higher efficacy of arterial treatment in inducing objective responses but neither of the two studies with a follow-up long enough to assess survival data showed a clear advantage for the patients receiving intraarterial chemotherapy. Gastroduodenitis, ulcers and chemical hepatitis are frequently observed in patients treated with intrahepatic arterial chemotherapy but their incidence can be substantially reduced by a careful surgical procedure during the implant of the arterial catheter and by a close follow-up during chemotherapy. Since toxicity can be serious and no definitive improvement of survival has been shown, this modality of treatment is still applicable only in an investigational setting.
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PMID:[Current results and prospects of intra-arterial chemotherapy in hepatic metastases of carcinoma of the colorectum]. 253 32


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