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Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

Adult↗

Mesenterico-left portal vein bypass in children with congenital extrahepatic portal vein thrombosis: a unique curative approach.

OBJECTIVES: Current management of extrahepatic portal vein thrombosis (EPVT) comprises endoscopic eradication therapy of esophageal varices and conventional shunt surgery. The authors have used the novel technique of mesenterico-left portal bypass (Rex shunt) in seven children with symptomatic EPVT, and report their results here. METHODS: Median age of the children was 12 years (range, 2-16 years). All children had portal hypertension with hypersplenism and recurrent bleeding from esophageal varices. Furthermore, one patient suffered from a severe hepatopulmonary syndrome. Preoperative evaluation included liver function tests, liver biopsy, hepatic duplex ultrasonography, and radiologic evaluation of the intrahepatic and extrahepatic vascular anatomy. The internal jugular vein was used as vein graft in all patients. RESULTS: Median follow-up period was 15 months (range, 3-28 months). Ultrasound scans revealed sufficient perfusion in all shunts (median, 35 cm/s; range, 28-60 cm/s). The intrahepatic portal perfusion in segment 4 improved from a median of 6 cm/s before surgery to 18 cm/s postoperatively. The platelet count increased within 3 months from a mean of 50,625/microL to 137,750/microL. The clinical signs of hypoxemia in the child with hepatopulmonary syndrome disappeared within 6 months. CONCLUSIONS: In accordance with the limited experience published by others, the authors' data confirmed the mesenterico-portal Rex shunt as the therapy of choice for children with EPVT. Furthermore, this report is the first to show that a hepatopulmonary syndrome can be abolished by mesenterico-portal Rex shunt.

Adolescent↗

Isolated varices over hepatic flexure colon indicating superior mesenteric venous thrombosis caused by uncinate pancreatic head cancer--a case report.

Very rare cases of varices involving right side colon were reported. Most of them were due to cirrhotic portal hypertension or other primary causes. No report case contributed to pancreatic cancer. Here, we reported a case of uncinate pancreatic cancer with the initial finding of isolated hepatic flexure colon varices. Following studies confirmed isolated varices involving hepatic flexure colon due to pancreatic cancer with occlusion of superior mesenteric vein. From this report, superior mesenteric vein occlusion caused by uncinate pancreatic head cancer should be considered as a differential diagnosis of colon varices.

Colon↗

Hepatic dysfunction in patients with extrahepatic portal venous obstruction.

BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) developing due to thrombotic occlusion of the portal vein in children is generally considered a benign disease. Whether hepatic dysfunction develops in these patients in the absence of a gastrointestinal bleed has not been well studied. MATERIALS AND METHODS: Forty-three patients with EHPVO who had not bled in the last 3 months were studied. Patients were divided into those with (group I) or without ascites (group II). Matched cirrhotic patients with ascites (group III) served as controls. Clinical, biochemical, ultrasonographic, and histopathological evaluation was carried out. Portal biliopathy was assessed in five patients in group I and in 12 patients in group II by cholangiography. RESULTS: Of 43 EHPVO patients, ascites was seen in nine (21%) patients (group I). Thirty-four patients had no ascites (group II). Serum ALT (54 +/- 24 vs. 34 +/- 10 IU/l, P < 0.01), albumin (3.2 +/- 0.3 vs. 3.7 +/- 0.4 g/dl, P < 0.01), and prothrombin time difference (9.0 +/- 4.5 vs. 2.4 +/- 1.9 s, P < 0.05) were deranged in patients in group I compared with group II. Patients in group I were 4 years older, and the duration of portal hypertension was longer than in group II (11.5 vs. 5.6 year, P < 0.05). Portal biliopathy changes were significantly more severe in group I than in group II patients. Ascites was high gradient in all the patients in group I and the serum-ascitic albumin gradient was comparable between groups I and III. None of the EHPVO patients, but four cirrhotic patients, developed spontaneous bacterial peritonitis during a follow-up of 11 +/- 4 months. CONCLUSIONS: Hepatic dysfunction in the form of ascites and deranged liver functions is not uncommon in patients with EHPVO, more so in patients with prolonged portal hypertension. Based on our data it would be worthwhile to study whether prolonged portal vein thrombosis in EHPVO patients could lead to progressive liver disease.

Adolescent↗

Combined intraarterial 5-fluorouracil and intramuscular interferon-alpha therapy for advanced hepatocellular carcinoma.

We report the case of a 66-year-old man with hepatic cirrhosis and multiple hypervascular tumors in both lobes of the liver as well as tumor thrombi in the portal vein. After unresectable hepatocellular carcinoma was diagnosed, transcatheter arterial embolization was considered to be difficult, because he had major portal vein thrombosis. Conventional ultrasonically-guided local treatments, such as percutaneous ethanol injection therapy and radiofrequency ablation, were also of no value because the tumors were huge and multiple. Ultimately, he was treated with a combination of intraarterial 5-fluorouracil and intramuscular interferon-alpha. After treatment, the multiple tumors became non-enhancing on contrast computed tomography scans and showed a marked decrease in size. There were no serious adverse effects (such as myelosuppression or hepatotoxicity) during treatment or follow-up and the patient is doing well at present. In conclusion, a combination of intraarterial 5-fluorouracil with intramuscular interferon-alpha appears to be useful for the management of advanced hepatocellular carcinoma, especially in patients for whom more aggressive treatment is not acceptable.

Aged↗

Acute pancreatitis complicated by infarction of the spleen and spinal cord.

Complications of acute pancreatitis may include local pancreatic necrosis with pseudocyst or abscess formation, and extrapancreatic manifestations such as pulmonary renal, hepatic, endocrine, and coagulation abnormalities. Coagulation abnormalities associated with acute pancreatitis usually present as thrombophlebitis or widespread microthrombi; most occur in the venous or capillary circulation. We report a rare case of acute pancreatitis complicated by pseudocyst formation, splenic vein thrombosis, splenic infarction, and spinal cord infarction, which resulted in paraplegia. An association between acute pancreatitis and spinal cord infarction has not been reported before.

Acute Disease↗

Hemobilia after percutaneous transhepatic biliary drainage: treatment with transcatheter embolotherapy.

Thirteen of 333 patients who underwent percutaneous biliary drainage (PBD) developed severe hemobilia. Hepatic arteriography successfully demonstrated the source of hemorrhage in all 13 patients. Lesions included hepatic artery pseudoaneurysm in nine, hepatic artery-bile duct fistulas in four, and a hepatic artery-portal vein fistula in one patient. Hemobilia occurred from 1 day to 1.8 years (mean, 100 days) following catheter placement. Embolization agents used included Hilal embolization microcoils, occluding spring emboli, cyanoacrylate, detachable balloons, and gelatin sponge pledgets. A single agent was used in eight cases (62%), multiple agents were used in four cases (31%), and in one case (7%), spontaneous thrombosis of the pseudoaneurysm occurred during catheter manipulation. In five patients, the source of the hemorrhage could only be demonstrated following removal of the biliary catheter(s) over guide wire(s). Initial embolization was successful in stopping hemobilia in 12 patients. One patient required repeat embolization after 4 months. Postembolization complications included hepatic abscess formation in two patients and a sterile hepatic infarct in one patient. This series indicates that transcatheter embolotherapy is an effective method for the treatment for severe hemobilia.

Aged↗

[Venous thrombosis in gastroenterology].

Venous thrombosis involving the digestive tract affects the suprahepatic veins and the terminal part of the inferior vena cava, the portal vein and its roots. The etiology and diagnosis of this condition have made considerable progress. A thrombogenic disease can now be recognized in 90% of cases of involvement of the suprahepatic veins, and 75% of portal involvements. The most frequent causes are primary myeloproliferative syndromes, paroxysmal nocturnal hemoglobinuria, hereditary deficiency in coagulation proteins and circulating anticoagulants. The cause of involvement of the portal vein also include insults during biliary surgery and abdominal infections, particularly those caused by Bacteroides fragilis. Mechanical involvement due to compression finally plays a minor role in the etiology. Noninvasive techniques of diagnosis are now available, including ultrasound, computed tomography and magnetic resonance imaging. The expression of obstruction of the suprahepatic veins predominantly consists in ascites and hepatomegaly. Thrombosis of the portal vein preserving the mesenteric arches usually remains asymptomatic until the intrahepatic block is revealed by a digestive hemorrhage caused by portal hypertension. Isolate involvement of the splenic vein exceptionally causes the rupture of gastric or esophageal collateral veins. The treatment should combine the prevention of further thromboses by anticoagulants and the specific treatment of the venous obstruction. In case of suprahepatic obstruction, there are several methods of restoring a canal of drainage for hepatic blood. Their indications depend on the patency of the inferior vena cava and of the portal vein. In case of portal obstruction, portal-systemic bypass is feasible only if one of the major roots of the portal vein still is patent.(ABSTRACT TRUNCATED AT 250 WORDS)

Budd-Chiari Syndrome↗

Infant pediatric liver transplantation results equal those for older pediatric patients.

METHODS: From July 1984 to July 1995, 99 pediatric patients underwent 127 orthotopic liver transplants (OLT) at the University of Wisconsin Children's Hospital. The patients were divided into four groups according to age at time of transplant: group I, 0 to 6 months (n = 20); group II, 6 to 12 months (n = 18); group III, 1 to 2 years (n = 10); and group IV, 2 to 18 years (n = 51). A retrospective analysis was performed to compare these four groups with regard to preoperative indications and demographics, intraoperative technique, complications, and survival. All patients were followed up for 2 to 13 years. RESULTS: Biliary atresia was the most common indication for OLT in all four groups. The average waiting period varied from 19+/-18 days for group I to 44+/-64 days for group IV. Reduced-size liver transplant (I, 41%; II, 52%; III, 28%; IV, 21%), split-liver transplant (I, 0%; II, 7.4%; III, 17%; IV, 2.9%), or whole-liver transplant techniques were used. Although postoperative Intensive Care Unit stay was longer for the 0- to 6-month-old patients (I, 20+/-64; II, 7.6+/-9; III, 13+/-17; IV, 6.8+/-14 days), the total hospital stay (I, 43+/-63; II, 33+/-34; III, 32+/-20; IV, 29+/-31 days) was similar for all patients. The incidence of hepatic artery thrombosis (I, 19%; II, 19%; III, 27%; IV, 16%), biliary tract complications (I, 4.8%; II, 15%; III, 20%; IV, 14%), and retransplantation (I, 9.5%; II, 41%; III, 33%; IV, 14%) were not significantly different between the four groups. Portal vein thrombosis (I, 9.5%; II, 11%; III, 6.6; IV, 0%) and primary nonfunction (I, 9.5%; II, 7.4%; III, 0%; IV, 3.1%) occurred more frequently in the 0- to 6-month and 6- to 12-month groups, however, the 1-, 5-, and 10-year survival rate for patients (I, 85%, 79%, 79%; II, 89%, 74%, 74%; III, 80%, 80%, 80%; IV, 84%, 75%, 75%, respectively) and primary liver allografts (I, 69%, 69%, 69%; II, 72%, 72%, 63%; III, 70%, 70%, 70%; IV, 71%, 57%, 57%, respectively) were not significantly different (P = .98 and P = .83). CONCLUSION: These results demonstrate that OLT can be effectively performed on infants of all ages and that OLT should not be delayed because of age.

Adolescent↗

Early MR follow-up of partial hepatectomy.

Twenty-seven patients were studied with MRI between 3 and 40 days following partial liver resection. Twenty-four patients had undergone major hepatectomy (three to six segments) and three had undergone minor hepatectomy (tumorectomy, one; bisegmentectomy, two). Indications for surgery were as follows: metastases (n = 16), hepatocellular carcinoma (n = 5), hemangioma (n = 3), focal nodular hyperplasia (n = 2), and cholangiocarcinoma (n = 1). A total of 36 MR examinations were performed using a 1.5 T superconducting unit. Three patients were studied three times and three patients were studied twice. The MR images were evaluated to detect and to characterize liver parenchymal abnormalities and intraabdominal fluid or blood collections as well as to assess vascular and/or graft patency. The MR images showed hepatic ischemia in two cases and allowed differentiation between intraabdominal hemorrhagic (n = 30 and nonhemorrhagic (n = 4) fluid collections. Gradient echo images allowed assessment of polytetrafluoroethylene graft patency as well as demonstration of iliac vein (one case) and portal vein (one case) thrombosis. The presence of surgical clips at the resection margins did not affect image quality.

Adult↗

Ultrasound and MR findings in acute Budd-Chiari syndrome with histopathologic correlation.

This report describes the sonographic and MR appearances of acute Budd-Chiari syndrome (BCS) in a 30-year-old woman. Current imaging techniques including duplex Doppler sonography and dynamic gadolinium-enhanced MRI were employed, and direct histopathologic correlation was made. Duplex Doppler sonography revealed a heterogeneous enlarged liver, no flow in the left and middle hepatic veins, and only trace abnormal flow in the distal-most right hepatic vein. Dynamic serial gadolinium-enhanced, spoiled gradient echo imaging demonstrated early homogeneous enhancement of an enlarged caudate lobe, as well as heterogeneously decreased enhancement of the remainder of the hepatic parenchyma. This differential enhancement pattern persisted on delayed imaging. Patent hepatic veins were not demonstrated on any sequence. Associated findings included hepatomegaly, ascites, and patent portal vasculature. These imaging findings were interpreted as consistent with acute BCS. Within 10 days, the patient underwent orthotopic liver transplantation. Histopathology demonstrated hepatic necrosis and hepatic venous thrombosis consistent with acute BCS.

Acute Disease↗

Long-term efficacy of immunoadsorbent plasmapheresis in a patient with Budd-Chiari syndrome due to antiphospholipid syndrome: case report with nine-year follow-up.

We describe the safety and efficacy of long-term immunoadsorbent plasmapheresis (IAPP) with dextran sulfate-cellulose bead columns in antiphospholipid syndrome (APS). IAPP was administered to a 38-year old male Japanese patient with APS with Budd-Chiari syndrome (BCS), who had presented with refractory lower leg skin ulcers and arterial and venous thromboses including BCS. After hepatic vein transluminal angioplasty was performed, the combination of corticosteroid, aspirin and IAPP was administered because of an underlying bleeding tendency related to liver dysfunction. From February 1994 to February 2003, a total of 228 procedures were performed. No further thrombosis-related symptoms or bleeding have occurred for more than nine years, suggesting that IAPP with dextran sulfate cellulose columns is safe and effective for APS in preventing additional thrombotic events. This IAPP supplements anticoagulation, antiplatelet, corticosteroid and immunosuppressant therapies.

Adult↗

Study on hepatocellular carcinoma-associated hepatic arteriovenous shunt using multidetector CT.

AIM: To investigate multidetector CT (MDCT) findings of hepatocelluar carcinoma (HCC)- associated hepatic arteriovenous shunt (HAVS) and to evaluate their clinical significance. METHODS: Thin-slice and dynamic enhancement MDCT of HAVS was performed on 56 patients with HCC. MDCT findings, including those of portal veins, hepatic veins, superior mesenteric veins, splenic veins, HCC foci, liver parenchyma without HCC foci, spleens, and thromboses in portal veins and hepatic veins, were all confirmed by digital subtract angiography and analyzed. RESULTS: MDCT demonstrated earlier enhancement of main portal trunks and/or the first order branches than that of superior mesenteric veins or splenic veins (n=31). One patient had strong early enhancement of left hepatic vein with thromboses in left hepatic vein and upper part of inferior vena cava and 1 patient had transient patchy enhancement peripheral to HCC foci in late hepatic arterial phase among them. It demonstrated stronger opacification of main portal trunks and/or the first order branches than that of superior mesenteric veins or splenic veins (n=18), and earlier enhancement of the second order and smaller branches of portal veins than that of main portal trunks (n=4), stronger opacification of the second order and smaller branches of portal veins than that of main portal trunks (n=3), with transient patchy enhancement (n=3) or wedge-shaped enhancement (n=4) peripheral to HCC foci in late hepatic arterial phase. Enhancement degree of HCC foci was all decreased. As for 49 patients with severe or moderate shunts, enhancement degree of liver parenchyma without HCC foci was increased with heterogeneous density, but enhancement degree of spleens was decreased. There were thromboses in main portal trunks and/or the first order branches in 32 patients. CONCLUSION: The main MDCT findings of HCC-associated HAVS are earlier enhancement and stronger opacification of portal veins and/or hepatic veins. Understanding of these findings will contribute to the diagnosis and prognosis of the disease and improve therapy for the patients.

Adult↗

[Efficacy of hepatic arterial infusion therapy for advanced hepatocellular carcinoma using 5-fluorouracil, epirubicin and mitomycin-C].

BACKGROUND/AIM: Prognosis of advanced hepatocellular carcinoma (HCC) treated by conventional therapies has been considered to be poor. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using FEM (5-fluorouracil, epirubicin, mitomycin-C) regimen for advanced HCC. METHODS: Eighteen patients received repeated HAIT using an implanted drug delivery system. Of the 18 patients, 8 patients had HCC with portal vein tumor thrombosis, 9 patients had recurrent HCC after transarterial chemoembolization (TACE) and 1 patient after surgical resection. The patients received 5-fluorouracil (330 mg/m(2), every week), epirubicin (30 mg/m(2), every 4 weeks) and mitomycin-C (2.7 mg/m(2), every 2 weeks). RESULTS: Mean age was 51 years. The response rate (complete response+partial response) by tumor size on abdominal CT was 38.9%. Survival ranged from 2 to 24 months and the median survival time was 8 months. The cumulative survival rate of responders group was significantly higher than non-responders group (p=0.0385). The mean levels of serum alpha-FP and PIVKA-II in responders group decreased after HAIT (3,179 ng/mL and 2,850 ng/mL) than before (11,218 ng/mL and 4,396 ng/mL), but not significantly. Chemotherapy-related side effects were nausea, vomiting and alopecia. Three patients had catheter-related complications. One patient developed gastric ulcer. CONCLUSIONS: HAIT using FEM regimen is a useful therapeutic option for patients with advanced HCC with portal vein tumor thrombosis or ineffective response to other therapies.

Adult↗

Cruveilhier-Baumgarten syndrome in which venous hum disappeared following endoscopic variceal sclerotherapy.

We report a case of Cruveihier-Baumgarten syndrome associated with portal vein thrombosis that developed, slowly during a 2-year period after endoscopic variceal sclerotherapy. The thrombosis led to the disappearance of the venous hum and the dilated abdominal wall veins characteristic of this syndrome. A 73-year-old woman was hospitalized for treatment of esophageal varices in April 1988. Her spleen was markedly enlarged, and the histologic findings of her liver were not consistent with hepatic cirrhosis, but with idiopathic portal hypertension. A venous hum was audible in the upper abdomen. Superior mesenteric angiography revealed a porto-systemic shunt vessel under the abdominal wall, originating from the umbilical vein. She was injected four times with a sclerosant, and this brought about disappearance of the esophageal varices. Two years after the first admission, the venous hum was no longer audible, but there was a recurrence of the esophageal varices. More than 2 years later (4 years after the first admission), ultasonographic study, computed tomography, and angiography showed a large thrombus, which completely obstructed the portal vein at the origin of the umbilical vein, and the development of collateral vessels, seen as a "cavernous transformation."

Aged↗

Prognostic value of indocyanine green and lidocaine kinetics for survival and chronic hepatic encephalopathy in cirrhotic patients following elective end-to-side portacaval shunt.

The objective of this study was to assess the prognostic value of spontaneous portosystemic shunting and liver function for survival and spontaneous hepatic encephalopathy after end-to-side portacaval shunt in cirrhotic patients. One hundred ninety-eight patients with variceal hemorrhage as shown by endoscopy were evaluated. Forty-five were excluded because of uncontrollable hemorrhage; 84 were rejected because they were poor operative risk, had portal vein thrombosis or had been previously treated with beta-blockers, sclerotherapy or surgery. The remaining 69 patients were enrolled in this prospective study. There were 43 patients with alcoholic cirrhosis, 23 with cryptogenic cirrhosis and three with primary biliary cirrhosis. The severity of liver disease was assessed according to the Pugh classification: 37 patients (54%) had Pugh's score 5 to 7, 26 (38%) had 8 to 10 and six (8%) had 11 to 12. Indocyanine green intrinsic clearance was used as a probe of preoperative liver function and lidocaine systemic availability as an index of spontaneous preoperative shunting. All the patients underwent an elective end-to-side portacaval shunt. The length of minimal follow-up was 40 months. One-year survival was 76% and 5-year survival was 46%. During follow-up, 25 patients died from their liver disease and 11 patients died from various causes unrelated to their liver disease. Spontaneous chronic encephalopathy occurred in 16 patients (23%). Age, Pugh's score, active alcoholism, indocyanine green intrinsic clearance and lidocaine systemic availability were tested as prognostic factors in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatic and splanchnic oxygenation during liver transplantation.

OBJECTIVE: To evaluate hepatic and splanchnic oxygenation during liver transplantation. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Ten adult patients undergoing liver transplantation. INTERVENTIONS: Standardized surgery and anesthesia without venovenous bypass. MEASUREMENTS AND MAIN RESULTS: Hepatic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in hepatic venous blood. Splanchnic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in portal venous blood and by gastric tonometry. Before reperfusion, the grafts were flushed with 1000 mL of acetated Ringer's solution and 400 mL of portal venous blood. The effluent blood from the graft was wasted and showed a mean pH of 6.86 and a lactate concentration of 9.4 mmol/L. Five minutes after portal reperfusion, most of the grafts produced lactate. Portal-hepatic venous P(CO2) difference ranged from 3 to 16 torr (0.4-2.1 kPa). By the time of restoration of the infrahepatic caval flow mean 24 mins later, eight of the grafts had stopped producing lactate. Mean hepatic venous oxygen tension was 47 torr (6.3 kPa), stabilizing to 41 torr (5.5 kPa) at the end of surgery. Acidosis resolved without pharmacologic interventions. Mean gastric mucosal pH was 7.29 during the anhepatic phase and 7.40 at the end of surgery. One of the patients developed hepatic arterial thrombosis intraoperatively. Her data were analyzed separately. Later, the other patients recovered with good liver function, whereas the patient with hepatic arterial thrombosis was successfully retransplanted. CONCLUSIONS: The liver grafts received well-oxygenated portal venous blood during reperfusion, despite the low values of gastric mucosal pH immediately before reperfusion. Hepatic oxygenation became adequate soon after reperfusion. In the patient with hepatic arterial thrombosis, the recovery of hepatic oxygenation was impaired and lactic acidosis persisted.

Adult↗