BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
Adolescent ; Adult ; Aged ; Antihypertensive Agents/*therapeutic use ; Benzimidazoles/*therapeutic use ; Blood Pressure ; Drug Therapy, Combination ; Female ; Humans ; Hypertension, Portal/complications/*drug therapy ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; Propranolol/*therapeutic use ; Prospective Studies ; Tetrazoles/*therapeutic use ; Treatment Outcome ; Young Adult

Enbucrilate ; adverse effects ; therapeutic use ; Female ; Humans ; Hypertension, Portal ; diagnosis ; etiology ; Liver Cirrhosis, Biliary ; drug therapy ; Middle Aged ; Pulmonary Embolism ; chemically induced ; diagnosis ; Sepsis ; chemically induced ; etiology

Pseudocirrhosis refers to a condition that shows changes in hepatic contour that mimic cirrhosis radiographically in the absence of the typical histopathological findings of cirrhosis. This condition has been observed in patients with cancer metastatic to the liver, both in those who have undergone prior systemic chemotherapy and those who have not. Pseudocirrhosis may cause difficulty in interpretation of the response to chemotherapy and hepatic decompression and complication of portal hypertension have a negative effect on the prognosis. We report on a case of breast cancer with liver metastases that showed cirrhotic changes during disease progression. Progression of liver metastases was confirmed by F18 fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We also performed ultrasound-guided liver biopsy and confirmed tumor infiltration with severe desmoplastic fibrosis. This case suggests the pathogenesis of pseudocirrhosis through histopathological findings and the role of PET-CT in evaluation of the response to chemotherapy in patients with pseudocirrhosis.
Biopsy ; Breast Neoplasms* ; Breast* ; Decompression ; Disease Progression ; Drug Therapy* ; Electrons ; Fibrosis ; Humans ; Hypertension, Portal ; Liver* ; Neoplasm Metastasis* ; Prognosis

Pseudocirrhosis refers to a condition that shows changes in hepatic contour that mimic cirrhosis radiographically in the absence of the typical histopathological findings of cirrhosis. This condition has been observed in patients with cancer metastatic to the liver, both in those who have undergone prior systemic chemotherapy and those who have not. Pseudocirrhosis may cause difficulty in interpretation of the response to chemotherapy and hepatic decompression and complication of portal hypertension have a negative effect on the prognosis. We report on a case of breast cancer with liver metastases that showed cirrhotic changes during disease progression. Progression of liver metastases was confirmed by F18 fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We also performed ultrasound-guided liver biopsy and confirmed tumor infiltration with severe desmoplastic fibrosis. This case suggests the pathogenesis of pseudocirrhosis through histopathological findings and the role of PET-CT in evaluation of the response to chemotherapy in patients with pseudocirrhosis.
Biopsy ; Breast Neoplasms* ; Breast* ; Decompression ; Disease Progression ; Drug Therapy* ; Electrons ; Fibrosis ; Humans ; Hypertension, Portal ; Liver* ; Neoplasm Metastasis* ; Prognosis

Portal hypertension, as one of the major complications of liver cirrhosis, is a common clinical syndrome characterized by an increased portal pressure and the formation of portal-systemic collaterals. Currently no ideal therapeutic agent has been available for portal hypertension. Sorafenib is an oral tyrosine kinase inhibitor that has been shown to significantly improve blood flow dynamics, inhibit angiogenesis, reduce liver fibrosis and decrease portal pressure in the treatment of portal hypertension. The authors review the progress in the research of sorafenib in the treatment of portal hypertension and the mechanisms of its actions.
Animals ; Humans ; Hypertension, Portal ; drug therapy ; Niacinamide ; analogs & derivatives ; pharmacology ; therapeutic use ; Phenylurea Compounds ; pharmacology ; therapeutic use

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

OBJECTIVE: To determine the safety and usefulness of a two-tiered approach to balloon-occluded retrograde transvenous obliteration (B-RTO) as a treatment for large gastric varices after portal hypertension. MATERIALS AND METHODS: 50 patients were studied who underwent B-RTO for gastric varices between October 2004 and October 2011 in our institution. The B-RTO procedure was performed from the right femoral vein and the B-RTO catheter was retained until the following morning. Distribution of sclerotic agents in the gastric varices on fluoroscopy was evaluated in all patients on days 1 and 2. When distribution of sclerotic agents in the gastric varices on day 1 had been none or very scanty even though the volume of the sclerotic agent infused was above the acceptable level, a second infusion was administered on day 2. When distribution was satisfactory, the B-RTO catheter was removed. RESULTS: In 8 (16%) patients, little or no sclerotic agent infused on day 1 was distributed in the gastric varices. However, on day 2, sclerotic agents were distributed in all gastric varices. Mean volume of ethanolamine oleate-iopamidol infused on day 1 was 24.6 mL and was 19.4 mL on day 2. Gastric varices were well obliterated with no recurrence. Complications caused by the sclerotic agent such as pulmonary edema or renal insufficiencies were not seen. CONCLUSION: When gastric varices are very large, a strategy involving thrombosis of only the drainage vein on the first day followed by infusing the sclerotic agent on the following day might be effective and feasible.
Adult ; Aged ; Aged, 80 and over ; Balloon Occlusion/*methods ; Catheters, Indwelling ; Collateral Circulation ; Drug Administration Schedule ; Esophageal and Gastric Varices/etiology/radiography/*therapy ; Female ; Femoral Vein ; Gastrointestinal Hemorrhage/etiology/*therapy ; Humans ; Hypertension, Portal/*complications ; Iopamidol/*administration & dosage/adverse effects ; Male ; Middle Aged ; Oleic Acids/*administration & dosage/adverse effects ; Recurrence ; Retrospective Studies ; Sclerosing Solutions/*administration & dosage/adverse effects ; Tomography, X-Ray Computed

We describe a case of systemic sclerosis (SSc) complicated with portal hypertensive ascites which did not improve with diuretics and ascitic drainage. When corticosteroid added, her ascites diminished dramatically. Though portal hypertension can be imputed to other causes, such as polycystic liver in this case, it can occur in limited SSc with positive anti-centromere antibody and respond to corticosteroid treatment.
Adrenal Cortex Hormones ; therapeutic use ; Aged ; Female ; Humans ; Hypertension, Portal ; diagnostic imaging ; drug therapy ; Radiography ; Scleroderma, Systemic ; diagnostic imaging ; drug therapy

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