Home About us Contact
|
Home About us Contact | ||
|
|
||
Hepatic Disease (hepatic + disease)
Selected AbstractsEvaluation of the Bromosulfophthalein 30-Minute Retention Test for the Diagnosis of Hepatic Disease in DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2000Bente Flatland The purpose of this study was to evaluate efficacy of bromosulfophthalein (BSP) retention testing in dogs with and without histopathologically confirmed hepatobiliary disease. Medical records of 150 dogs with hepatobiliary disease having both a BSP test and hepatic biopsy were retrieved. Histopathologic slides of liver tissue were reviewed, and dogs were classified according to 1 of 11 histopathologic categories. Twenty-five clinically normal random-source dogs were used as controls for hepatic biopsy and BSP testing. No dogs suffered adverse effects due to BSP administration. BSP retention was significantly (P < .05) higher in hospitalized (13.9%) than control (3.2%) dogs, but the test could not distinguish between hospitalized dogs with different types of hepatobiliary disease. Sensitivity, specificity, and predictive values of BSP retention as a test for hepatic disease were calculated. Using 5.0% as a cutoff for normal BSP retention resulted in a specificity of 88% and a sensitivity of 76%. Using 6.0% as a cutoff for normal BSP retention resulted in a specificity of 100% and a sensitivity of 70%. Dogs of this study having BSP retention of >6% had at least an 86% chance of having an abnormal liver. We concluded that continued use of BSP retention testing is warranted as a noninvasive diagnostic test for liver disease in dogs. [source] Review article: management of hepatic disease following haematopoietic cell transplantALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006G. B. McDONALD Summary Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug-induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant. Pre-transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes. This review covers pre-transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long-term survivors. [source] Intravenous Levetiracetam as first-line treatment of status epilepticus in the elderlyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2010J. Fattouch Fattouch J, Di Bonaventura C, Casciato S, Bonini F, Petrucci S, Lapenta L, Manfredi M, Prencipe M, Giallonardo AT. Intravenous Levtiracetam as first-line treatment of status epilepticus in the elderly. Acta Neurol Scand: 2010: 121: 418,421. © 2010 John Wiley & Sons A/S. Background,,, Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs. Objective,,, The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly. Methods,,, We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring. Results/conclusions,,, In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly. [source] Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients,HEPATOLOGY, Issue 5 2009Francisca H. H. Linn Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13,26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2,30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 ± 38 versus 91 ± 23 ,g: P = 0.01) and serum non,ceruloplasmin-bound copper concentrations (11 ± 2 versus 7 ± 1 ,g/dL: P = 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering. (HEPATOLOGY 2009.) [source] Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice,HEPATOLOGY, Issue 4 2007Megan H. Keane The marked deficiency of peroxisomal organelle assembly in the PEX2,/, mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to evaluate the response to bile acid replenishment in this disease state. PEX2 mutant liver has severe but transient intrahepatic cholestasis that abates in the early postnatal period and progresses to steatohepatitis by postnatal day 36. We confirmed the expected reduction of mature C24 bile acids, accumulation of C27,bile acid intermediates, and low total bile acid level in liver and bile from these mutant mice. Treating the PEX2,/, mice with bile acids prolonged postnatal survival, alleviated intrahepatic cholestasis and intestinal malabsorption, reduced C27,bile acid intermediate production, and prevented older mutants from developing severe steatohepatitis. However, this therapy exacerbated the degree of hepatic steatosis and worsened the already severe mitochondrial and cellular damage in peroxisome-deficient liver. Both untreated and bile acid,fed PEX2,/, mice accumulated high levels of predominantly unconjugated bile acids in plasma because of altered expression of hepatocyte bile acid transporters. Significant amounts of unconjugated bile acids were also found in the liver and bile of PEX2 mutants, indicating a generalized defect in bile acid conjugation. Conclusion: Peroxisome deficiency widely disturbs bile acid homeostasis and hepatic functioning in mice, and the high sensitivity of the peroxisome-deficient liver to bile acid toxicity limits the effectiveness of bile acid therapy for preventing hepatic disease. (HEPATOLOGY 2007;45:982,997.) [source] Lung metastases after liver resection or cryotherapy for hepatic metastasis from colorectal cancer,there is a difference!HPB, Issue 2 2006T. D. Yan Background. The most common site of colorectal extra-abdominal metastases is the lung. The relative risk of lung metastases after resection and cryotherapy has not previously been compared. Methods. All patients underwent an extensive preoperative staging including clinical examination, abdominal computed tomography (CT) and abdominal angio-CT to assess their hepatic disease. Two groups of patients were compared in this study (hepatic resection alone and hepatic cryotherapy with or without resection). A retrospective analysis of prospectively collected data was performed to assess the incidence and disease-free interval of pulmonary metastasis after surgical treatment of colorectal liver metastasis. Results. This paper clearly shows two differences regarding pulmonary metastases between patients treated with resection only and cryotherapy with or without resection. Among the 10 clinical variables, cryotherapy had the greatest correlation with pulmonary metastases (p=0.004). A patient who undergoes hepatic resection only has a probability of 35% for developing pulmonary recurrence, compared with 51% following cryotherapy. Cryotherapy was also independently associated with shorter pulmonary disease-free interval (p=0.036). Conclusion. There clearly is a higher risk of pulmonary metastasis after cryotherapy than after resection, whether this is related to selection of patients or a direct deleterious procedural effect requires more study. [source] Pathological study of idiopathic portal hypertension with an emphasis on cause of death based on records of Annuals of Pathological Autopsy Cases in JapanJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2007Seiko Sawada Abstract Background and Aim:, Idiopathic portal hypertension (IPH) is thought to be benign if bleeding gastroesophageal varices can be controlled or prevented. A recent autopsy of a woman with IPH who died of hemorrhagic intestinal infarction related to mesenteric thrombosis prompted the authors to examine the terminal antemortem features and causes of death of IPH. Methods:, Autopsy cases registered as IPH from 1986 to 1997 were surveyed in the records of the Annuals of Pathological Autopsy Cases in Japan, with permission from the Japanese Society of Pathology. The records of 65 of these cases were collected and examined pathologically. Results:, It was found that the most frequent cause of death in these cases was (i) bacterial infection (20 cases). The next three causes of death were directly or indirectly related to hepatic disease or its altered portal hemodynamics as follows: (ii) progressive hepatic failure (16 cases); (iii) massive hemorrhage from ruptured gastroesophageal varices (11 cases); and (iv) hemorrhagic intestinal infarction due to mesenteric venous thrombosis (5 cases). Although portal venous thrombosis was closely associated with (iv), (ii) and (iii) seemed not to be associated with portal venous thrombosis. In addition, intracranial hemorrhage and other heterogeneous factors were identified as the cause of death in five cases and eight cases, respectively. Conclusion:, These results suggest that progressive hepatic failure and intestinal hemorrhagic infarction should be considered in addition to rupture of gastroesophageal varices when monitoring patients with IPH. Clinicians should be also aware of severe bacterial infection and intracranial hemorrhage as a fatal complication of IPH. [source] Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2007Tzung-Yan Lee The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg,1 YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-, compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg,1 having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and ,8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction. [source] Surgical resection of primary and metastatic hepatic malignancies following portal vein embolizationJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2009Brian Mailey MD Abstract Background Portal vein embolization (PVE) has been used to induce hypertrophy in future liver remnants (FLRs) in preparation for major hepatic resection. We report our initial experience with PVE and identify potential predictors of unresectability following PVE. Methods Patients with primary and metastatic hepatic malignancies (n,=,20) who underwent PVE between 2004 and 2008 were categorized by surgical resection status and clinicopathologic factors were compared. Results The cohort had the following histologies: colorectal adenocarcinoma (45%, n,=,9), hepatocellular carcinoma (20%), cholangiocarcinoma (20%), and other (15%). Seven patients (35%) had previous liver-directed or regional therapy; 55% subsequently underwent successful liver resection, whereas 45% were deemed unresectable. Patients who underwent successful resection had tumor shrinkage after PVE compared to unresectable patients (% change in maximal tumor diameter, ,6% vs. +45%, respectively; P,=,0.027) and had a lower rate of baseline liver function test abnormality (0% vs. 56%, respectively; P,=,0.004). Resected patients had an 83% 5-year overall survival. Conclusions Baseline liver dysfunction may predict subsequent unresectable hepatic disease following PVE and tumor progression after PVE appears to increase the likelihood for finding unresectable hepatic disease. Select patients should be considered for PVE with careful surveillance during the period of FLR hypertrophy. J. Surg. Oncol. 2009;100:184,190. © 2009 Wiley-Liss, Inc. [source] Serum Bile Acids Concentrations in Healthy and Clinically III Neonatal FoalsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2007Michelle Henry Barton Background:Reference ranges for serum bile acids (SBA) concentration are well established in healthy adult horses. Increased values are indicative of hepatic disease. Hypotheses: SBA concentrations are significantly greater in the neonatal period compared with mature horses, and illness in the neonatal period will further increase SBA. Animals:Ten healthy mature horses, 12 healthy foals, and 31 clinically ill foals. Methods:Prospective cross-sectional study. Blood samples were obtained once from the mature horses, from healthy foals immediately after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of age; and from ill foals less than 1 month of age at the time of admission to the Veterinary Teaching Hospital. SBA concentrations were determined enzymatically and by radioimmunoassay. Total and direct bilirubin and triglyceride concentrations were measured, as well as sorbitol dehydrogenase (SDH) and ,-glutamyltransferase (GGT) activities. Results:There was a significant negative correlation between age and SBA concentration. Compared with mature horses, SBA concentrations were significantly greater in healthy foals at each collection time over the first 6 weeks of life. Radioimmunoassay values were lower than enzymatic SBA values, with increasing bias as the mean difference between values increased. When comparing age-matched values between healthy and ill foals, there were no significant differences in SBA. None of the ill foals had a primary diagnosis of hepatic disease. There was no significant correlation between the SBA concentration and the bilirubin or triglyceride concentrations or the GGT activity. There was a significant direct correlation between increased SBA and serum SDH activity in healthy foals only. Conclusion and Clinical Importance: SBA concentrations in foals are significantly higher in the early neonatal period, underscoring the importance of using age-matched references when evaluating clinical pathology values during the neonatal period. [source] Retrospective Evaluation of Partial Parenteral Nutrition in Dogs and CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2002Daniel L. Chan The purpose of this retrospective study was to evaluate the use of partial parenteral nutrition (PPN) in dogs and cats. The medical records of all dogs and cats receiving PPN between 1994 and 1999 were reviewed to determine signalment, reasons for use of PPN, duration of PPN administration, duration of hospitalization, complications, and mortality. Complications were classified as metabolic, mechanical, or septic. One hundred twenty-seven animals (80 dogs and 47 cats) were included in the study, accounting for 443 patient days of PPN. The most common underlying diseases were pancreatitis (n = 41), gastrointestinal disease (n = 33), and hepatic disease (n = 23). Median time of hospitalization before initiation of PPN was 2.8 days (range, 0.2,10.7 days). Median duration of PPN administration was 3.0 days (range, 0.3,8.8 days). Median duration of hospitalization was 7 days (range, 2,20 days). In the 127 animals receiving PPN, 72 complications occurred. These included metabolic (n = 43), mechanical (n = 25), and septic (n = 4) complications. The most common metabolic complication was hyperglycemia (n = 19), followed by lipemia (n = 17) and hyperbilirubinemia (n = 6). Most complications were mild and did not require discontinuation of PPN. Ninety-three (73.2%) of the 127 patients were discharged. All 4 animals with septic complications were discharged from the hospital. The presence, type, and number of complications did not impact the duration of hospitalization or outcome. However, animals that received supplemental enteral nutrition survived more often than those receiving PPN exclusively. Although PPN seems to be a relatively safe method of providing nutritional support, future studies are warranted to determine its efficacy. [source] Evaluation of the Bromosulfophthalein 30-Minute Retention Test for the Diagnosis of Hepatic Disease in DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2000Bente Flatland The purpose of this study was to evaluate efficacy of bromosulfophthalein (BSP) retention testing in dogs with and without histopathologically confirmed hepatobiliary disease. Medical records of 150 dogs with hepatobiliary disease having both a BSP test and hepatic biopsy were retrieved. Histopathologic slides of liver tissue were reviewed, and dogs were classified according to 1 of 11 histopathologic categories. Twenty-five clinically normal random-source dogs were used as controls for hepatic biopsy and BSP testing. No dogs suffered adverse effects due to BSP administration. BSP retention was significantly (P < .05) higher in hospitalized (13.9%) than control (3.2%) dogs, but the test could not distinguish between hospitalized dogs with different types of hepatobiliary disease. Sensitivity, specificity, and predictive values of BSP retention as a test for hepatic disease were calculated. Using 5.0% as a cutoff for normal BSP retention resulted in a specificity of 88% and a sensitivity of 76%. Using 6.0% as a cutoff for normal BSP retention resulted in a specificity of 100% and a sensitivity of 70%. Dogs of this study having BSP retention of >6% had at least an 86% chance of having an abnormal liver. We concluded that continued use of BSP retention testing is warranted as a noninvasive diagnostic test for liver disease in dogs. [source] Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 geneJOURNAL OF VIRAL HEPATITIS, Issue 4 2003H. J. Kwun Summary. Transcription of p21 was activated in hepatitis C virus (HCV) Core-expressing HepG2 cells where its upstream p53 was stabilized. However, this effect was not absolutely required for the activation of p21 by Core, as demonstrated in Hep3B cells. In addition, an opposite effect on the transcription of p21 was observed in NIH3T3 and primary hepatocytes, where p53 was not decreased by Core. To explain the p53-independent regulation of p21 by Core, we identified a Core-responsive element between positions ,74 and ,83 of the p21 promoter, exactly overlapped with a tumour growth factor , (TGF- ,)/butyrate responsive element. Furthermore, we demonstrated that Core could activate the p21 through the element by stimulating a butyrate pathway, whereas this was inhibited through a TGF- , pathway. The opposing effects of Core protein on the transcription of p21 might be important in understanding the progression of hepatic disease in HCV-positive patients. [source] Review article: management of hepatic disease following haematopoietic cell transplantALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006G. B. McDONALD Summary Hepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft-versus-host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug-induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant. Pre-transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes. This review covers pre-transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long-term survivors. [source] Dietary iron overload in the African and hepatocellular carcinomaLIVER INTERNATIONAL, Issue 6 2007Michael C. Kew Abstract Dietary iron overload occurs commonly in parts of sub-Saharan Africa. It results from the consumption of large volumes of traditional beer that is home-brewed in iron pots or drums and consequently has a high iron content. The liver becomes iron overloaded and may develop portal fibrosis or, less often, cirrhosis. A genetic predisposition to the condition has been suggested, but no putative gene has yet been identified. Although originally believed not to cause hepatocellular carcinoma, recent case,control studies have shown African Blacks with dietary iron overload to be at increased risk for the tumour and a causal association has been confirmed in an animal model. The mechanisms of iron-induced malignant transformation are yet to be fully characterised, but the close association between cirrhosis and hepatocellular carcinoma in patients with hereditary haemochromatosis and the lesser association in those with dietary iron overload, suggests that chronic necroinflammatory hepatic disease contributes to the malignant transformation. Increased hepatic iron may, however, also be directly carcinogenic. Probable mechanisms include the generation of reactive oxygen intermediates and the resultant chronic oxidative stress that damages hepatocytes and proteins, causes lipid peroxidation, and induces strand breaks, DNA unwinding, and mutations in tumour-suppressor genes and critical DNA repair genes. [source] Promising Diagnostic Biomarkers for Primary Biliary Cirrhosis Identified With Magnetic Beads and MALDI-TOF-MSTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009Yong-Zhe Li Abstract (PBC) is not a rare disease worldwide. Most patients are diagnosed at the advanced stage, primarily because there are not yet any valid biomarkers available for early diagnosis. Useful biomarkers are absolutely necessary for early detection of PBC. Fortunately, the use of MALDI-TOF-MS and pattern recognition software has been successful in finding specific markers for the early detection of the disease. To screen for potential protein biomarkers in the serum for diagnosing PBC, MALDI-TOF-MS combined with magnetic beads and pattern recognition software was used to investigate 119 serum samples from 44 patients with PBC, 32 controls with other hepatic disease, and 43 healthy controls. A total of 69 discriminant m/z peaks were identified as being associated with PBC. Of them, the m/z peaks at 3445, 4260, 8133, and 16,290 were used to construct a model for the diagnosis of PBC. This diagnostic model can distinguish PBC from non-PBC controls with a sensitivity of 93.3% and a specificity of 95.1%. In our blind test, it demonstrated good sensitivity and specificity: 92.9% and 82.4%, respectively. These results indicate that useful serum biomarkers for PBC can be discovered by MALDI-TOF-MS combined with the use of magnetic beads and pattern recognition software. The pattern of multiple markers provides a powerful and reliable diagnostic method for PBC with high sensitivity and specificity. Anat Rec, 292:455,460, 2009. © 2009 Wiley-Liss, Inc. [source] Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease (Br J Surg 2009; 96: 175,184)BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2009J. A. Sųreide The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Authors' reply: Treatment of liver metastases from neuroendocrine tumors in relation to the extent of hepatic disease (Br J Surg 2009; 96: 175,184)BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2009A. Frilling No abstract is available for this article. [source] Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2009A. Frilling Background: Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. Methods: A novel classification of LM from NET was established based on their localization and presentation. Results: From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76·4, 63·9 and 46·5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III. Conclusion: The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Combined hepatocellular and cholangiocarcinomaCANCER, Issue 7 2002Demographic, clinical, prognostic factors Abstract BACKGROUND Tumors with combined hepatocellular and cholangiocellular features are well known histopathologically but their clinical behavior is poorly understood. The objectives of the current study were to define the demographic profile of the patients in whom these uncommon tumors occur and to evaluate treatment outcome in comparison with that in patients with either hepatocellular carcinoma (HCC) or peripheral cholangiocarcinoma (CC) alone. METHODS Twenty-seven patients with combined tumors were identified from a prospective database. Pathologic specimens were analyzed to confirm the diagnosis. Demographics, clinical data, and survival were analyzed. Outcome after resection was compared with that of patients with CC and with a matched group of patients with HCC. RESULTS The gender distribution of the combined tumors (52% men and 48% women) was intermediate between HCC (67% men and 33% women) and CC (30% men and 70% women) (P = 0.03). The incidence of positive hepatitis B or C serology and cirrhosis was similar in patients with combined tumors and those with CC (15% and 0% vs. 13% and 4%, respectively); similarly, patients of Asian heritage constituted 7% and 9%, respectively, of the patients with these tumors. By contrast, cirrhosis (41%) and positive hepatitis serology (56%) were far more common in patients with HCC, and 19% of these patients were of Asian heritage. Twenty-one of 27 patients with combined tumors (78%) underwent resection. All 6 patients with combined tumors that were not amenable to resection died of disease within 18 months. After resection, the 5-year survival was lowest in patients with combined tumors (24%) but was not significantly different from that in patients with CC (33%) or HCC (37%). The liver was the most common site of recurrence in all three groups. CONCLUSIONS The demographic and clinical features of patients with combined tumors were most similar to those of patients with CC. Most important, combined tumors were not found to be associated with chronic liver disease; consequently, the resectability rate was higher for these tumors than typically is reported for HCC. Resection was associated with long-term survival in some patients, but recurrent hepatic disease was common. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance. Cancer 2002;94:2040,6. © 2002 American Cancer Society. DOI 10.1002/cncr.10392 [source] Bowel movement frequency, medical history and the risk of gallbladder cancer death: A cohort study in JapanCANCER SCIENCE, Issue 8 2004Kiyoko Yagyu Few risk factors for gallbladder cancer have been identified with sufficient statistical power, because this cancer is rare. The present study was conducted to evaluate the association of bowel movement frequency and medical history with the risk of death from gallbladder cancer using the data set from a large-scale cohort study. A total of 113,394 participants (42.0% males), aged 40 to 89 years, were followed up for 11 years. Information on the medical history of selected diseases, history of blood transfusions, frequency of stools, and tendency toward diarrhea at baseline was collected through a self-administered questionnaire. The Cox proportional hazard model was used to estimate the hazard ratio (HR). During the follow-up period, a total of 116 deaths (46 males, 70 females) from gallbladder cancer were identified. After adjustments for age and gender, history of hepatic disease (HR: 2.28; 95% confidence intervals (95% CI): 1.24,4.21), frequency of stool, and tendency toward diarrhea (HR: 0.26; 95% CI: 0.08-0.83) were found to be significantly associated with the risk of death from gallbladder cancer. Compared with those who had a stool at least once a day, the HR was 2.06 (95% Cl: 0.82,5.18) for those who had a stool less than once in 6 days (P for trend=0.050). In this prospective study, constipation and a history of hepatic disease were found to elevate the risk of gallbladder cancer death, whereas a tendency toward diarrhea diminished it. [source] Hypertrophic osteoarthropathy in two children with cholestatic hepatic diseaseACTA PAEDIATRICA, Issue 8 2005M Katsicas Abstract Aim: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant. Conclusion: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention. [source] Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn,HEPATOLOGY, Issue 3 2008Chun-Ping Cui Hepatic stimulating substance (HSS) was first isolated from weanling rat liver in 1975 and found to stimulate hepatic DNA synthesis both in vitro and in vivo. Since then, mammalian and human HSS have been investigated for their potential to treat hepatic diseases. However, the essential nature in composition and structure of HSS remain puzzling because HSS has not been completely purified. Heating, ethanol precipitation, and ion-exchange chromatographies had been carried out to isolate the protein with specific stimulating activity from newborn calf liver, and [3H]thymidine deoxyribose (TdR)/bromodeoxyuridine (BrdU) incorporation and carboxyfluorescein diacetate succinimidyl ester (CFSE)-based proliferation assay to determine the bioactivity in vitro and in vivo. We report the purification of a novel 30-kDa protein from a crude extract of calf liver HSS. This protein is a member of the leucine-rich acidic nuclear protein family (LANP) and has been named hepatopoietin Cn (HPPCn). Studies of partially hepatectomized (PH) mice show that levels of HPPCn messenger RNA (mRNA) increase after liver injury. Furthermore, the recombinant human protein (rhHPPCn) was shown to stimulate hepatic DNA synthesis and activate signaling pathways involved in hepatocyte proliferation in vitro and in vivo. Conclusion: HPPCn is a novel hepatic growth factor that plays a role in liver regeneration. (HEPATOLOGY 2008;47:986,995.) [source] Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis CHEPATOLOGY RESEARCH, Issue 8 2007Rosāngela Teixeira Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source] The Burden of Disease and the Cost of Illness Attributable to Alcohol Drinking,Results of a National StudyALCOHOLISM, Issue 8 2010Helena Cortez-Pinto Background and Aims:, The World Health Organization estimated that 3.2% of the burden of disease around the world is attributable to the consumption of alcohol. The aim of this study is to estimate the burden of disease attributable to alcohol consumption in Portugal. Methods:, Burden and costs of diseases attributable to alcohol drinking were estimated based on demographic and health statistics available for 2005, using the Disability-Adjusted Life Years (DALY) lost generated by death or disability. Results:, In Portugal, 3.8% of deaths are attributable to alcohol (4,059 of 107,839). After measuring the DALY generated by mortality data, the proportion of disease attributable to alcohol was 5.0%, with men having 5.6% of deaths and 6.2% of disease burden, while female figures were, respectively, 1.8 and 2.4%. Considering the sum of death and disability DALYs, liver diseases represented the main source of the burden attributable to alcohol with 31.5% of total DALYs, followed by traffic accidents (28.2%) and several types of cancer (19.2%). As for the cost of illness incurred by the health system, our results indicate that ,95.1 millions are attributable to alcohol-related disease admissions (liver diseases, cancer, traffic accidents, and external causes) while the ambulatory costs of alcohol-related diseases were estimated in ,95.9 million, totaling ,191.0 million direct costs, representing 0.13% of Gross Domestic Product and 1.25% of total national health expenditures. An alternative analysis was carried out using higher consumption levels so as to replicate aggregate alcohol consumption statistics. In this case, DALYs lost increased by 11.7% and health costs by 23%. Conclusion:, Our results confirm that alcohol is an important health risk factor in Portugal and a heavy economic burden for the health system, with hepatic diseases ranking first as a source of burden of disease attributable to alcohol. [source] Induction of umbilical cord blood,derived ,2m,c-Met+ cells into hepatocyte-like cells by coculture with CFSC/HGF cellsLIVER TRANSPLANTATION, Issue 6 2005Yunfang Wang Several studies have indicated that adult stem cells derived from bone marrow (BM) and cord blood (CB) can differentiate into hepatocyte-like cells. This ability is important for the treatment of hepatic diseases with BM or CB as a potential approach. However, methods are still being developed for the efficient induction of stem cell differentiation and expansion to get enough cells to be useful. In the present study, we enriched a subset of umbilical cord blood ,2m,c-Met+ cells (UCBCCs) and investigated the combination effect of liver nonparenchymal cells (cirrhotic fat-storing cells [CFSCs]) and hepatocyte growth factor (HGF) on the induction of UCBCCs into hepatocyte-like cells. UCBCCs were cocultured with CFSC/HGF feeder layers either directly or separately using insert wells. Flow cytometric analysis showed that most UCBCCs were CD34+/,CD90+/,CD49f+CD29+Alb+AFP+. After cocultured with transgenic feeder layers for 7 days, UCBCCs displayed some morphologic characteristics of hepatocytes. Reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence cell staining proved that the induced UCBCCs expressed several hepatocyte specific genes including AFP, Alb, CYP1B1 and cytokeratins CK18 and CK19. Furthermore, the induced cells displayed liver specific functions of indocyanine green (ICG) uptake, ammonium metabolism and albumin secretion. Hence, our data have demonstrated that UCBCCs might represent a novel subpopulation of CB-derived stem/progenitor cells capable of successful differentiation into hepatocyte-like cells when incubated with CFSC/HGF cells. In conclusion, not only HGF but also CFSCs and/or the secreted extracellular matrix (ECM) have been shown to be able to serve as essential microenvironment for hepatocyte differentiation. (Liver Transpl 2005;11:635,643.) [source] IFN-, gene therapy by intrasplenic hepatocyte transplantation: a novel strategy for reversing hepatic fibrosis in Schistosoma japonicum -infected micePARASITE IMMUNOLOGY, Issue 1 2001Lihuang Zhang Liver-targeted gene therapy using hepatocyte as recipient cells has recently been documented to be effective in treatment of numerous hepatic diseases, such as metabolic diseases and liver carcinoma. IFN-, elicits antipreliferative and antifibrogenic activity in a variety of mesenchymal cells, including hepatic satellite cells. To investigate the antifibrogenic response of liver gene therapy mediated by intrasplenic transplantation of gene-modified hepatocytes, normal mouse liver cell line BNL CL.2 cells were transfected with murine IFN-, gene (BNL.IFN-,) in vitro, and transplanted intrasplenically into Schistosoma japonicum -infected mice. The amounts and distribution of IFN-, (which inhibits collagen synthesis), TGF-, (which stimulates collagen synthesis) and extracellular matrix, including type I and III collagen, were detected. In mice infected with S. japonicum and then treated with BNL.IFN-,, an increase of IFN-, and decrease of TGF-,1 were detected at 20 weeks postinfection compared to untreated S. japonicum -infected mice. Immunohistochemical analysis showed that S. japonicum infection induced a marked increase of type I and III collagen synthesis. Whereas, 4 weeks after treatment with BNL.IFN-,, net synthesis rates of type I and III collagen were markedly decreased in the liver of infected mice. In addition, a decreased expression of TGF-,1 and its receptor TGF-,RII in the liver of BNL.IFN-,-treated mice was also observed. Moreover, the decrease in TGF-,1 and TGF-,RII protein approximately paralleled the decrease in their mRNA expression, which was detected by RNA dot blotting. The data indicate that intrasplenic transplantation of IFN-, gene-modified hepatocyte can be a candidate approach to treat hepatic fibrosis. [source] Stereoselective binding of human serum albuminCHIRALITY, Issue 3 2006Victor Tuan Giam Chuang Abstract Stereoselectivity in binding can have a significant effect on the drug disposition such as first-pass metabolism, metabolic clearance, renal clearance, and protein and tissue binding. Human serum albumin (HSA) is able to stereoselectively bind a great number of various endogenous and exogenous compounds. Various experimental data suggested that the two major drug-binding cavities, namely, site I and site II, do not seem to be the stereoselective binding sites of HSA. Stereoselective binding of HSA under disease conditions such as renal and hepatic diseases was found to be enhanced. In addition, site-to-site displacement of a site II-specific drug by another site II-specific drug was found to be stereoselective, too. Endogenous compounds such as long-chain fatty acids and uremic toxins are likely to cause combined direct and cascade effects that contribute to the preferential binding of a particular drug enantiomer. Taking together the findings of other studies, it is highly possible that the stereoselective binding site exists at the interface of the subdomains. © 2006 Wiley-Liss, Inc. Chirality [source] | |||||||||||||||||||||||||||||||