Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sorafenib (BAY 43-9006) is a novel oral bis-aryl urea compound originally developed as an inhibitor to RAF kinase for its anti-proliferative property. It also inhibits receptor tyrosine kinases of multiple pro-angiogenic factors such as VEGFR-2/3, Flt-3/ and PDGFR-beta. The combination of both its anti-proliferative and anti-angiogenic properties makes sorafenib an attractive agent in cancer treatment. Phase I studies demonstrated that sorafenib was well tolerated, and the recommended phase II dose was 400 mg twice daily continuously. Common toxicities included skin toxicity (rash and hand-foot syndrome), gastrointestinal toxicities (nausea and diarrhea) and fatigue. Anti-tumor activities were observed in multiple tumors types including renal cell carcinoma and hepatocellular carcinoma. Randomized phase III studies in these tumor types are ongoing, and results are eagerly waited.
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PMID:Sorafenib (BAY 43-9006): review of clinical development. 1866 47

A 52-year-old man visited our hospital complaining of anorexia and fatigue two months after receiving orthotopic liver transplantation for hepatocellular carcinoma. A laboratory investigation demonstrated a clinical picture of obstructive jaundice. T-tube cholangiography showed biliary stricture over the anastomotic site. Percutaneous transluminal balloon dilatation and stenting was attempted but failed. Magnetic resonance cholangiography showed possible tumor recurrence over the site of the anastomotic biliary stricture. A biopsy sample was obtained via ultrasound-guided aspiration and histopathological study revealed inflammatory and fibrotic changes. With high suspicion of recurrence of the hepatocellular carcinoma, surgical exploration was performed and an intraoperative frozen section proved the recurrence. We thus diagnosed this case as a recurrence of hepatocellular carcinoma after liver transplantation. To our knowledge, there have been no previous reports of early tumor recurrence after liver transplantation being the cause of an anastomotic biliary stricture.
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PMID:Recurrence of hepatocellular carcinoma after liver transplantation presenting as anastomotic biliary stricture. 1880 93

Hepatocellular carcinoma (HCC) annually causes about one million deaths. Because of advanced stage at diagnosis, HCC carries a five-year survival rate of less than 5% in patients diagnosed with unresectable disease. Incidence for HCC is higher in men and individuals of Asian descent, where viral hepatitis, a leading cause of HCC, is endemic. This article will provide an overview of the complex symptom management of patients with HCC. The occurrence of multiple symptoms, including pain, fatigue, weight loss, and obstructive syndromes (e.g., ascites, jaundice) in patients with HCC is common. Because of limitations in the efficacy of current treatment options, aggressive symptom management is key to preserving physical functioning and quality of life in patients with HCC. A multidisciplinary team approach to symptom management of patients with HCC is critical, with oncology nurses playing an integral role.
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PMID:Symptom management in hepatocellular carcinoma. 1884 32

We report the case of a patient with hepatocellular carcinoma who was admitted to our hospital with fatigue and edema of lower extremities. Transthoracic echocardiographic examination revealed a mobile echogenic cavoatrial mass that infiltrated the inferior vena cava and extended along the vessel protruding into the right cardiac cavities. The differential diagnosis included a tumor mass originating from the liver and subsequently infiltrating the inferior vena cava and extending into the right cardiac cavities or a large thrombus formed on the tumor mass that infiltrated the inferior vena cava.
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PMID:The role of myocardial contrast echocardiography to assess the origin of a mass in right cardiac cavities. 1912 11

Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved in the EU for the treatment of hepatocellular carcinoma. Monotherapy with sorafenib prolongs overall survival and delays the time to progression in patients with advanced hepatocellular carcinoma who are not candidates for potentially curative treatment or transarterial chemoembolization. Sorafenib is generally well tolerated in patients with advanced hepatocellular carcinoma. Thus, sorafenib represents an important advance in the treatment of advanced hepatocellular carcinoma and is the new standard of care for this condition. The bi-aryl urea sorafenib is an oral multikinase inhibitor that inhibits cell surface tyrosine kinase receptors (e.g. vascular endothelial growth factor receptors and platelet-derived growth factor receptor-beta) and downstream intracellular serine/threonine kinases (e.g. Raf-1, wild-type B-Raf and mutant B-Raf); these kinases are involved in tumour cell proliferation and tumour angiogenesis. In vitro, dose-dependent inhibition of cell proliferation and induction of apoptosis was seen with sorafenib in human hepatocellular carcinoma cells lines. Sorafenib demonstrated dose-dependent antitumour activity in a murine xenograft model of human hepatocellular carcinoma. Steady-state plasma concentrations were reached within 7 days in patients with advanced, refractory solid tumours who received twice-daily oral sorafenib. Metabolism of sorafenib occurs primarily in the liver and is mediated via cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase 1A9. In advanced hepatocellular carcinoma, differences in sorafenib pharmacokinetics between Child-Pugh A and B patients were not considered clinically significant. Sorafenib may be associated with drug interactions. For example, sorafenib exposure was reduced by an average 37% with concomitant administration of the CYP3A4 inducer rifampicin (rifampin); sorafenib concentrations may also be decreased by other CYP3A4 inducers. Monotherapy with oral sorafenib 400 mg twice daily prolonged median overall survival and delayed the median time to progression in patients with advanced hepatocellular carcinoma, according to the results of two randomized, double-blind, placebo-controlled, multicentre, phase III trials (the SHARP trial and the Asia-Pacific trial). There was no significant difference between sorafenib and placebo recipients in the median time to symptomatic progression in either trial. The vast majority of patients included in these trials were Child-Pugh A. Combination therapy with sorafenib plus doxorubicin did not delay the median time to progression to a significant extent compared with doxorubicin alone in patients with advanced hepatocellular carcinoma, according to the results of a randomized, double-blind, phase II trial. However, the median durations of overall survival and progression-free survival were significantly longer in patients receiving sorafenib plus doxorubicin than in those receiving doxorubicin alone. Combination therapy with sorafenib plus tegafur/uracil or mitomycin also showed potential in advanced hepatocellular carcinoma, according to the results of noncomparative trials. Monotherapy with oral sorafenib was generally well tolerated in patients with advanced hepatocellular carcinoma, with a manageable adverse effect profile; diarrhoea and hand-foot skin reaction were consistently the most commonly occurring drug-related adverse events in clinical trials. In the SHARP trial, drug-related adverse events of any grade occurring in significantly more sorafenib than placebo recipients included diarrhoea, hand-foot skin reaction, anorexia, alopecia, weight loss, dry skin, abdominal pain, voice changes and 'other' dermatological events. A similar tolerability profile was seen in the Asia-Pacific trial. As expected given the addition of a chemotherapy agent, the adverse event profile in patients with advanced hepatocellular carcinoma who received combination therapy with sorafenib plus doxorubicin differed somewhat to that seen with sorafenib monotherapy in the SHARP trial. In patients receiving sorafenib plus doxorubicin, the most commonly occurring all-cause adverse events (all grades) included fatigue, neutropenia, diarrhoea, elevated bilirubin levels, abdominal pain, hand-foot skin reaction, left ventricular dysfunction, hypertension and febrile neutropenia.
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PMID:Sorafenib: a review of its use in advanced hepatocellular carcinoma. 1922 77

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.
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PMID:New approaches in the therapy of hepatitis C in dialysis patients. 1925 44

The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.
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PMID:Clinical aspects of acute intermittent porphyria in northern Sweden: a population-based study. 1940 33

The purposes of this study were to (a) explore the relationships among sleep disturbance, fatigue, and depression and (b) test whether depression mediates the effect of sleep disturbance on fatigue in patients with hepatocellular carcinoma (HCC). A cross-sectional study was conducted with a total of 77 patients with HCC. All participants completed questionnaires that included the Brief Fatigue Inventory-Taiwan Form, the Pittsburgh Sleep Quality Index-Taiwan Form, and the depression subscale of the Taiwanese version of the Hospital Depression and Anxiety Scale. Path analysis was used to test the mediation role of depression. Fatigue, sleep disturbance, and depression are positively interrelated and co-occur in patients with HCC. Moreover, depression completely mediates the effects of sleep disturbance on fatigue. These findings suggest that depression is an important mechanism underlying the relationship between sleep disturbance and fatigue for patients with HCC. This is the first study to explore the phenomenon of symptom clustering in sleep disturbance, fatigue, and depression in patients with HCC and to investigate the mediating role of depression that underlies the relationship between sleep disturbance and fatigue. The current findings are of clinical importance because they suggest the need to consider simultaneous management of sleep disturbance, fatigue, and depression.
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PMID:The mediating effects of depression on sleep disturbance and fatigue: symptom clusters in patients with hepatocellular carcinoma. 1966 95

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.
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PMID:Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report. 1967 68

Raf kinases and vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinases are potential molecular targets for obtaining both anti-tumor cell progression and anti-angiogenesis effects in cancers, including hepatocellular carcinoma (HCC). Sorafenib is an oral multi-kinase inhibitor that mainly targets Raf kinases and receptor tyrosine kinases associated with angiogenesis (VEGFR-2/-3, PDGFR-beta). A global randomized controlled trial (RCT) of sorafenib versus placebo conducted in patients with advanced HCC demonstrated the beneficial effects of the drug on the time-to-progression and overall survival. Furthermore, a RCT with a similar design to that of the global trial conducted in the Asia-Pacific region also demonstrated the efficacy of the drug. The most common treatment-related adverse events of sorafenib were found to be diarrhea, fatigue, and skin toxicity, namely, hand-foot syndromes and rash. Based on the results of the RCTs, sorafenib has been established as a standard agent for systemic chemotherapy in HCC patients with metastatic disease or transcatheter arterial chemoembolization (TACE)-refractory disease who are not suitable candidates for local treatments. The efficacy and safety of sorafenib in patients with moderate liver dysfunction have not been confirmed to date and more data are needed. Development of new therapeutic methods is needed for the treatment of advanced HCC in the future; clinical trials of sorafenib-based combination therapy, second-line therapy after sorafenib failure, and adjuvant therapy after local treatments are warranted in HCC patients.
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PMID:Sorafenib for the treatment of unresectable hepatocellular carcinoma. 1970 58


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