BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). METHODS: The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. RESULTS: The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CONCLUSION: CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Angiogenic Proteins/genetics/metabolism ; Animals ; Bile Ducts/surgery ; C-Reactive Protein/*analysis/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; Hepatic Veins/abnormalities ; Hepatocytes/cytology/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lithocholic Acid/pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/etiology ; Liver Diseases/metabolism/*pathology ; Male ; Microscopy, Fluorescence ; Mitochondria/drug effects/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Serum Albumin/genetics/metabolism

Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments.
Adolescent ; Child ; Double-Blind Method ; Female ; Follow-Up Studies ; Fontan Procedure ; Heart Defects, Congenital ; drug therapy ; pathology ; surgery ; Humans ; Liver ; drug effects ; pathology ; Male ; Palliative Care ; Prognosis ; Sulfonamides ; administration & dosage ; Treatment Outcome

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use

Transarterial chemoembolization (TACE) is one of the most effective therapies for unresectable hepatocelluar carcinoma or metastatic hypervascular tumors. Abscess occurring in the other organs beside the liver after TACE is a complication that often occurs, sometimes potentially fatal. We report a case of spinal epidural abscess occurred after liver abscess complicated by TACE in a patient with metastatic neuroendocrine tumors to the liver. A 67-year-old female underwent TACE first for the metastatic lesions to liver, with a history of pancreatoduodenectomy for the primary pancreatic neuroendocrine tumor. Four days after TACE, sudden high fever occurred, and liver abscess was found on abdominal CT. Two days later, back pain and radiating pain to the right leg occurred, and lumbar spine MRI showed spinal epidural abscess. After intravenous antibiotics for 8 weeks and partial laminectomy, the patient recovered and was discharged without complications.
Aged ; Anti-Bacterial Agents/therapeutic use ; Carcinoma, Hepatocellular/secondary/*therapy ; Chemoembolization, Therapeutic/*adverse effects ; Epidural Abscess/*etiology/microbiology/surgery ; Escherichia coli/isolation & purification ; Escherichia coli Infections/drug therapy ; Female ; Humans ; Laminectomy ; Liver Abscess/*etiology ; Liver Neoplasms/secondary/*therapy ; Lumbar Vertebrae/microbiology/radiography ; Magnetic Resonance Imaging ; Neuroendocrine Tumors/pathology/surgery ; Pancreaticoduodenectomy ; Tomography, X-Ray Computed

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and alpha-smooth muscle actin (alpha-SMA) were conducted with control group. The immunohistochemical stains for CD31 and alpha-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.
Actins/metabolism ; Antigens, CD31/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Chemotherapy, Adjuvant ; Colonic Neoplasms/*drug therapy ; Fluorouracil/therapeutic use ; Humans ; Hypertension, Portal/etiology ; Immunohistochemistry ; Leucovorin/therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Liver Neoplasms/secondary/surgery ; Male ; Middle Aged ; Organoplatinum Compounds/*administration & dosage/adverse effects/therapeutic use ; Splenomegaly/*diagnosis/etiology ; Thrombocytopenia/etiology ; Tomography, X-Ray Computed

OBJECTIVETo investigate the expression of Toll-like receptor 4 (TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression.

METHODSMale Wistar Rats were randomly divided into sham-operated group (n=6), BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50 mg/kg) (n=12). Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days. The protein level of TLR4 in the liver tissue was examined by Western blotting.

RESULTSIn 14-day BDL group, the protein level of TLR4 significantly increased to 6.53∓1.11 folds of that in the sham group (P<0.05), and was lowered significantly to 1.71∓0.41 folds and 0.95∓0.38 folds following perindopril and losartan treatments for 14 days. TLR4 expression significantly increased to 6.51∓0.87 folds and 5.64∓0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments (P<0.05).

CONCLUSIONTLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can be lowered by perindopril and losartan treatmemts for 14 days.

Animals ; Bile Ducts ; surgery ; Down-Regulation ; drug effects ; Ligation ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Losartan ; pharmacology ; Male ; Perindopril ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; genetics ; metabolism

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.
Adult ; Antineoplastic Agents/*adverse effects/therapeutic use ; Chemotherapy, Adjuvant ; Esophageal and Gastric Varices/chemically induced ; Female ; Fibrosis ; Humans ; Hypertension, Portal/chemically induced/*diagnosis ; Liver/pathology ; Organoplatinum Compounds/*adverse effects/therapeutic use ; Positron-Emission Tomography ; Rectal Neoplasms/*drug therapy/surgery ; Splenomegaly/chemically induced ; Tomography, X-Ray Computed

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.
Adult ; Antineoplastic Agents/*adverse effects/therapeutic use ; Chemotherapy, Adjuvant ; Esophageal and Gastric Varices/chemically induced ; Female ; Fibrosis ; Humans ; Hypertension, Portal/chemically induced/*diagnosis ; Liver/pathology ; Organoplatinum Compounds/*adverse effects/therapeutic use ; Positron-Emission Tomography ; Rectal Neoplasms/*drug therapy/surgery ; Splenomegaly/chemically induced ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the efficacy and toxicity of paclitaxel with low-dose cisplatin and 5-fluorouracil continuous infusion in the treatment of advanced gastric carcinoma.

METHODSThe patients were treated with paclitaxel liposome 60 mg/m(2) i.v. gtt on d1, 8, 15, DDP 15 mg×m(-2)×d(-1) by i.v. gtt on d1-5, 5-Fu 500 mg×m(-2)×d(-1) by civ for 120 h, administered every 21 days.

RESULTSOut of the whole group, 3 cases achieved CR, 29 cases achieved PR with an ORR of 54.2% and median TTP of 7.1 months. Out of 40 cases in the primary treatment, 3 cases achieved CR, 22 cases achieved PR with an ORR of 62.5% and median TTP of 7.6 months. Out of 20 evaluable retreated cases, no case achieved CR, 7 cases achieved PR with an ORR of 36.8% and median TTP 6.3 months. The main toxicities were hematological toxicities, nausea and vomiting of grade I-II.

CONCLUSIONThe combination regimen of paclitaxel, low-dose cisplatin and 5-fluorouracil is effective and well tolerated for patients with advanced gastric carcinoma, especially for primary treatment cases. It is worthy of further study.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; surgery ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leukopenia ; chemically induced ; Liposomes ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; Survival Rate ; Vomiting ; chemically induced ; Young Adult