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Post-transplant IVC occlusion and thrombosis treated with tPA, heparin, and sharp recanalization.

Complete inferior vena cava (IVC) thrombosis can be a lethal complication in a liver transplant recipient. The case of a 52-year-old liver transplant recipient, who developed complete IVC as well as left iliofemoral thrombosis, is reported. After treatment with combined tissue plasminogen activator (tPA) and heparin, the IVC was successfully recanalized with sharp dissection, balloon dilatation, and stent placement.

Blood Vessel Prosthesis Implantation↗

Treatment of Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Several modalities are available for the treatment of HCC, and decisions regarding the optimal choice of therapy are based on tumor burden and severity of liver disease. Classification systems are helpful for prognostic purposes and to guide in the choice of therapy. Surgical resection is a mainstay of therapy for patients with solitary small tumors and preserved liver function (noncirrhotic or Child-Pugh class A cirrhotic patients without portal hypertension). Unfortunately, a minority of patients is eligible for resection, and postoperative recurrence or de novo HCC is common. Liver transplantation offers the best chance of curing HCC in cirrhotic patients. Patients with a solitary tumor less than 5 cm or no more than three tumors each 3 cm or less have a survival rate of 70% with less than 20% recurrence at 5 years. Access to liver transplantation is limited by organ availability, and tumor progression during the waiting period can lead to ineligibility. Ethanol injection and radiofrequency ablation are effective modalities to ablate small tumors (generally <5 cm) in patients who are not candidates for resection or liver transplantation. These modalities can also be used to treat HCC prior to liver transplantation. Transarterial chemoembolization is used to treat patients with multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic agents are infused into the tumor via the hepatic artery along with embolic material in order to induce tumor necrosis. This technique should be used in selective patients with relatively preserved liver function, absence of portal vein thrombosis, or encephalopathy. Limited data exist to support the use of this modality as a primary treatment option for small HCC. Chemotherapeutic or hormonal therapies have a limited role in the management of patients with HCC. Despite mixed outcomes, we routinely use the somatostatin analog octreotide in advanced, multifocal HCC. Emerging therapies should focus on treatment of small tumors and targeted pharmacologic therapy for advanced disease.

Journal Article↗

Transarterial chemoembolisation for advanced hepatocellular carcinoma: results from a North American cancer centre.

AIMS: In Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefi of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions fo HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population. MATERIALS AND METHODS: This was a single centre prospective cohort study. Child-Pugh A cirrhosis or better patients wit unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis wer assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m(2) doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2-3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response. RESULTS: The survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE. CONCLUSIONS: The survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe sideeffects require close monitoring and prompt intervention.

Aged↗

Bile duct injury as a major cause of stenosis and occlusion in transjugular intrahepatic portosystemic shunts: comparative histopathologic analysis in humans and swine.

PURPOSE: A comparative histologic analysis of human and swine transjugular intrahepatic portosystemic shunts (TIPS) was performed to investigate factors limiting TIPS patency and to further develop an animal model for TIPS. MATERIALS AND METHODS: Twenty-one human and 13 porcine shunts were evaluated by means of gross inspection, histologic evaluation, and electron microscopy. RESULTS: Severe stenosis (> 75% narrowing) or occlusion was detected with portal venography in nine of the 21 human shunts (48%) and in 10 of 13 porcine shunts (77%). Gross or histologic evidence of a substantial biliary fistula was observed in seven of nine porcine shunts and in seven of eight human shunts with severe parenchymal tract stenosis or occlusion. No evidence of substantial bile duct injury was identified in the 13 human shunts or two swine shunts with patent, nonstenotic parenchymal tracts (P < .01, Fisher exact). Histologic findings in porcine shunts mimicked human tissue responses, including a metaplastic proliferation of bile duct epithelium at sites of bile duct transection. CONCLUSION: Bile duct transection and bile leak are significantly associated with TIPS parenchymal tract abnormalities in patients and swine. TIPS in swine created with the Wallstent faithfully reproduce gross morphologic and histologic changes observed in patients.

Animals↗

Esophageal varices: current management in children.

The treatment of esophageal variceal hemorrhage is still the subject of some controversy. The main causes of portal hypertension in children are portal vein thrombosis or cirrhosis, most commonly caused by biliary atresia. Many treatment options are available including endoscopic, radiographic, and surgical strategies. In general, children with presinusoidal obstructions have preserved hepatic synthetic function, and, therefore, treatment options include endoscopic strategies or portosystemic shunts, each with advocates. For children with advanced liver disease, liver transplantation offers the only chance for cure, so primary treatment of variceal bleeding should be by endoscopic means or transjugular intrahepatic portosystemic shunt (TIPS). Each modality has specific advantages and disadvantages, and treatment recommendations must therefore be tailored to the individual on a case-by-case basis, largely dependent on the expertise and experience of the health care team.

Child↗

[Angiography following liver transplantation].

39 angiographic studies performed on 34 out of 150 patients following a total of 159 orthotopic liver transplantations until the year 1989 were reviewed in retrospect. All of the studies were carried out within a period of two months after transplantation (1-45 days). Angiographic techniques remain the "gold standard" for the assessment of vascular problems after liver transplantation. Arterial complications were seen in fourteen cases (8.8%); complications confined to the portal and inferior caval veins were found in six (3.8%) and twelve cases (7.5%), respectively. Angiography yielded normal postoperative findings in nine patients.

Adolescent↗

Use of intraoperative ultrasonography during hepatic transplantation.

The aim of this study was to evaluate if intraoperative vascular ultrasonography is of clinical value in the perioperative management of hepatic transplant patients. Fifteen intraoperative ultrasonographic examinations were performed on 13 patients (five female, eight male) during transplantation. These patients had clinically suspected vascular compromise. Among the 13 patients studied intraoperatively, five were correctly diagnosed as having hemodynamically significant vascular compromise. Of the intraoperative vascular sonographic examinations, the results of 13 were in concordance with the surgical impression as to whether further intervention was necessary or if the procedure could be terminated. Intraoperative sonography demonstrates potential to be of aid to the surgeon in recognition of vascular compromise.

Adult↗

Portal hypertension.

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephalopathy or alter the survival rate. Both PCS and DSRS prevent rebleeding, yet neither alters the survival rate for alcoholic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Peripancreatic vascular occlusions as a complication of pancreatitis.

In the case records of patients with a pancreatic inflammatory state (1,268 patients) during a 15-year period (1972-1986) we found 11 patients, who were diagnosed as having vascular obstruction in association with pancreatitis. The incidence was thus found to be 0.9%. This incidence was three times higher in chronic than in acute pancreatitis. Vessels near the head of the gland were the most frequently affected. Arteries predominated (64%). A laparotomy had been previously performed on seven patients. Thus manipulation of the pancreas may be an important co-factor in pathogenesis. Ten patients (91%) died. Only four (36%) were correctly diagnosed before autopsy. The diagnostics and clinical implications of various forms of vascular occlusions with pancreatitis are discussed.

Acute Disease↗

Simultaneous measurement of hepatic arterial and portal venous flows by transit time ultrasonic volume flowmetry.

Simultaneous measurement of the hepatic artery and the portal vein was performed successfully upon 15 anesthetized patients during abdominal operations with the use of transit time ultrasonic volume flowmeter. The hepatic arterial flow, portal venous flow and total hepatic flow were 267.3 +/- 21.2, 746.4 +/- 41.3 and 1,010.7 +/- 52.7 milliliters per minute, respectively. The ratio of hepatic arterial flow to portal venous flow was 0.36 +/- 0.03. Temporary occlusion of the portal vein resulted in a significant increase in hepatic arterial flow (23.6 +/- 4.3 per cent, p less than 0.01), whereas temporary occlusion of the hepatic artery did not alter portal venous flow significantly. Occlusion of the common hepatic artery induced a significant decrease in hepatic arterial flow (p less than 0.05), but did not alter portal venous flow significantly. The results of this approach had useful clinical meanings in one patient in whom the Appleby's operation was performed in which sufficient hepatic arterial flow was needed after the common hepatic artery was ligated. Data are presented for hepatic circulation measured by transit time ultrasonic volume flowmeter, which is a good device to use to assess portal venous flow as well as hepatic arterial flow with reproducibility and stability.

Adult↗

[Hypercoagulability in patients with veno-occlusive disease after bone marrow transplantation].

BACKGROUND: Veno-occlusive disease (VOD) leads to obliteration of small intrahepatic venules and is one of three most important complications with fatal outcome after bone marrow transplantation (BMT). The etiology of VOD is not completely understood. Endothelial cell injury induced by the conditioning myeloablative radiochemotherapy with subsequent activation of the coagulation cascade seems to be a crucial step in the pathogenesis of the disease. PATIENTS AND METHODS: We investigated tissue plasminogen activator (tPA), its main inhibitor (PAI-1) and the natural anticoagulants protein C and S by enzymimmunoassay prospectively in 32 bone marrow transplant recipients. RESULTS: VOD developed in four patients. They presented with extremely elevated levels of PAI-1 after BMT whereas tPA levels remained low. Additionally a transient decrease of protein S was found one week after BMT which was more pronounced in VOD patients. No protein C deficiency was observed. CONCLUSION: Our data suggest that hypofibrinolysis due to an excess of PAI-1 may be involved in the pathogenesis of VOD. The determination of PAI-1 may be useful to recognize the development of VOD and facilitate the decision for thrombolytic therapy with rtPA. A decrease of protein S may play a role as a cofactor in the early phase after BMT.

Bone Marrow Transplantation↗

Hepatic coma recovered after interventional obliteration for ileocecal-inferior vena cava shunt--report of one case.

We performed interventional angiography (IVA) in a patient with liver cirrhosis (LC) and hepatoma (HCC) who experienced repeated attacks of unconsciousness due to hyperammonemia caused by ileocecal-inferior vena cava (IC-IVC) shunt and succeeded in the treatment. We report the results below. The patient, 53-year-old male, underwent endoscopic injection sclerotherapy for esophageal varix due to LC followed by splenectomy for pancytopenia in 1986. He made good progress. However intraarterial anticancer therapy was conducted for HCC in 1994. From that time hepatic coma began to appear and its frequency gradually increased. Hepatic coma occurred once every 3 weeks from June 1996. He was thus admitted to our hospital. Hematobiochemical testes showed that ammonia level was 297 mcg/dl. Albumin 2.8d/dl, and Total-Bilirubin 10.78 mg/dl. Arterioportography from superior mesenteric artery showed most of portal blood flowed away from the liver though the ileocolic vein to IVC. We decided to conduct IVA for treatment. Specially, a 6Fr balloon catheter was inserted from the right inguinal region into a shunt to the portal vein though IVC by the Seldinger technique. The balloon was inflated in the shunt to close the shunt. Six ml of 5% ethanolamime oleate with iopamidol was injected because retrograde angiography showed that iopamidol was flowed out via testicular vein to IVC. The balloon catheter was retained for 24 hours. Angiography, conducted from the catheter again 24 hours later, showed that the shunt was occluded, blood ammonia level was 71 mcg/dl after occlusion. Hepatic coma was not observed after treatment. We encountered a very rare case who repeated hepatic comas due to IC-IVC shunt and recovered dramatically after IVA.

Angiography↗

[Veno-occlusive syndrome with acute liver dystrophy following decarbazine therapy of malignant melanoma (author's transl)].

Case report about death due to veno-occlusive liver disease following Dacarbazine treatment: 9 years after surgical treatment of malignant melanoma of the trunk a 68-years old patient developed lymph node metastases in the right axilla, which were removed immediately by surgical excision. One month before the patient had undergone surgical treatment of empyema of the gallbladder: Cholecystectomy and appendectomy were performed, postoperative recovery was uncomplicated. On account of the second lymph node metastasis within nine months adjuvant treatment with Dacarbazine was agreed and started one month later. After having performed the first course of treatment without any hints to intolerance the patient suddenly exhibited severe shock symptoms on the fourth day of the second course. Clinically residual myocardial infarct or pulmonary embolism were assumed, but could not be verified. The patient delivered increasing hepatomegaly. A massive increase in transaminase values was noted. Hemostasiologic changes with decreased Quick value occurred. The patient died of cerebral hemorrhage five days after beginning the second Dacarbazine cycle. Autopsy findings were severe liver cell necroses as well as liver vein thromboses, no metastases of melanoma could be found. Hepatotoxicity of Dacarbazine and the mechanism of liver vein thrombosis are discussed with special regards to possible hemostasiologic changes and sensibilisation due to Dacarbazine and/or previous liver cell damage.

Aged↗

Liver transplantation in children weighing less than 10 kilograms.

Orthotopic liver transplantation (OLT) remains a major medical and surgical challenge in small pediatric patients. From April 2003 through October 2005, 17 infants (each of whom weighed less than 10 kg) underwent the procedure. Four were girls and 13 were boys (mean age, 15.7 +/- 9.3 months [range, 2-36 months]; mean weight at the time of transplantation, 7.4 +/- 2.6 kg [range, 6-10 kg]). All transplants were obtained from living-related donors. Sixteen left lateral segments and 1 left lobe were transplanted. The median graft-to-recipient weight ratio was 3.5% +/- 1.2% (range, 1.5%-6.1%). During the early postoperative period, hepatic arterial thrombosis was identified in 2 infants, and a biliary leak in 1. Hepatic arterial thrombosis was treated by reanastomosis with polytetrafluoroethylene grafting in the first patient and by surgical embolectomy in the second. The biliary leak was treated with percutaneous drainage. In 1 infant, portal vein stenosis, which was identified during the late postoperative period, was treated by percutaneous balloon dilatation. At this time, 14 (82.3%) infants were alive, exhibiting good graft function at a median follow-up of 11 months (range, 2-36 months). Three infants died: 1 on postoperative day 47 from adult respiratory distress syndrome, 1 on postoperative day 12 from sepsis, and 1 on postoperative day 65 from sepsis associated with EBV infection. Episodes of acute rejection, which occurred in 5 patients, were treated with pulse steroid therapy. On follow-up, histologic examination revealed hepatocellular carcinoma in 2 infants and Burkitt's lymphoma in 1 infant. Our data confirm that extensive use of living-related donors in liver transplantation can result in an excellent outcome for small pediatric patients.

Anastomosis, Surgical↗

[Nonsurgical treatment of hepatocellular carcinoma].

Hepatocellular carcinoma is responsible in France for approximately 5,500 deaths per year. Incidence rates are growing and the general status of patients is improving mainly because of earlier diagnosis and improvement in the treatment of complications of liver cirrhosis. In most of the cases the severity of the underlying liver disease is the prominent prognostic factor. Its treatment remains a difficult challenge for oncologists. Unfortunately surgery is usually contraindicated. Most trials of systemic chemotherapy are disappointing with poor response rates and severe side effects; new drugs and direct delivery in the hepatic artery appear to be of interest. Results with interferon are interesting but requires more studies. The lack of efficacy of antiandrogenic and antiestrogenic treatments were recently demonstrated; a recent randomized study showing the interest of somatostatin requires confirmation. Reports on radiotherapy are anecdotals. A lot of studies using liver directed therapies were conducted worldwide. Percutaneous ethanol injections (PEI) are well tolerated and are highly effective in small solitary tumors (> 70% of complete necrosis) but less in larger tumors; recurrences are frequent. No randomized trial have been performed concerning PEI but survival rates seem similar to those of surgery. A randomized controlled trial recently demonstrates that injection of acetic acid is more effective than injection of ethanol. Chemoembolization was extensively studied because of the demonstration of objective responses but all trials failed to demonstrate an improvement in survival. Intraarterial injection of radioactive Lipiodol achieves the same response rate and the same survival than chemoembolization but is significantly best tolerated. This treatment is superior to best supportive cares in patients with portal vein thrombosis. In conclusion, despite the fact that this disease is very frequent we have currently too many treatment options and are lacking of simple rules. The best treatment remains prevention, and the efficacy of hepatitis B vaccination was recently demonstrated in Taiwan.

Antineoplastic Agents↗