Implantable hepatic arterial infusion device: placement without laparotomy via an intercostal artery.
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Biomedical subjects
Publications and source records attributed to D Azoulay.
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BACKGROUND: Hepatitis C virus infection (HCV) is associated with a variety of extrahepatic disorders such as membranoproliferative glomerulonephritis (MPGN), which is generally due to cryoglobulinemia. After liver transplantation for HCV cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver graft is poorly effective and may induce intractable graft rejection. METHODS: We describe the cases of four liver transplant recipients treated with ribavirin for HCV-related glomerulopathy and nephrotic syndrome. RESULTS: The nephrotic syndrome was attenuated or disappeared during ribavirin therapy, and patients showed a marked decrease in proteinuria and an increase in albuminemia. The syndrome relapsed in two patients when ribavirin therapy was stopped, and a favorable response was again obtained in both cases when the treatment was resumed. The main adverse effect of ribavirin was anemia in two patients with renal impairment. No graft rejection occurred. CONCLUSIONS: These findings suggest that continuous therapy with low doses of oral ribavirin may improve the proteinuria of hepatitis C-related glomerulonephritis, at least in liver transplant recipients.
Azathioprine-induced veno-occlusive disease of the liver mainly described after kidney transplantation is as rare as severe with a high mortality due to acute portal hypertension and liver failure. A kidney-transplanted patient with severe azathioprine-induced veno-occlusive disease of the liver and worsening despite drug discontinuation was treated by emergency transjugular intrahepatic portosystemic shunt. Whereas the veno-occlusive disease was controlled, the patient developed severe intractable portosystemic encephalopathy successfully treated by a stent reducer maintaining a certain degree of portal diversion. Twelve months after transjugular intrahepatic portosystemic shunt, liver function was normalized and the stent was thrombosed with a subnormal liver histology. Thirty-six months after transjugular intrahepatic portosystemic shunt the patient is alive with normal liver function tests and kidney graft function. Transjugular intrahepatic portosystemic shunt for treatment of severe veno-occlusive disease of the liver is an alternative to tide the patient over until recovery of liver function.
Liver transplantation is a treatment for hepatocellular carcinoma in cirrhosis which is both recognized, because potentially radical, and controversial because associated with a high risk of recurrence. This study reports the results of a consecutive series of 125 patients transplanted for hepatocellular carcinoma in cirrhosis over an 11-year period. Liver transplantation was indicated because of the tumour in 92 cases (74%) and the tumour was an incidental finding in 13 cases (10%) or was discovered on histological examination of the hepatectomy specimen in 20 cases (16%). The operative mortality at two months was 4% with a 20% morbidity, due to vascular (6%) or biliary (14%) complications. Tumour recurrence was observed in 26 patients (21%) Recurrence was exceptional in the incidental or histological forms of hepatocellular carcinoma (5%) and more frequent when the tumour constituted the indication for transplantation (27%). The risk of recurrence and the survival were significantly influenced by the maximal tumour diameter (greater than 30 mm), the number of tumour nodules (greater than 3) and the presence of portal invasion. Inclusion of these factors in patient selection during the second phase of the study allowed a reduction of the risk of recurrence from 33 to 11% and improvement of the 3-year post-transplantation survival from 53 to 76%. Tumours less than or equal to 30 mm in diameter, with no more than 3 nodules, and without portal invasion are ideal indications for transplantation. Tumours with more than 3 nodules and larger than 30 mm appear to constitute a contraindication to transplantation, unless tumour reduction can be achieved by chemoembolization. Intermediate forms of hepatocellular carcinoma between these two extreme forms are possible indications for transplantation, depending on the availability of liver transplants.
Cyclosporine toxicity is still a significant problem in the early period after liver transplantation. The monoethylglycinexylidide (MEGX) test performed in the donor has been suggested as a reliable test to predict liver graft function in the recipient. The MEGX test was performed in 50 consecutive donors, and the clinical course of recipients, metabolic parameters of the grafts, and cyclosporine levels were followed in detail for 10 days. Two patients died of sepsis and were excluded. Renal and/or neurological toxicity appeared in 15 of the remaining 48 patients (31%). In the 6 with neurological problems, MEGX values were low (41, 47, 50, 60, 94, and 101 micrograms/L). Nine patients had transient elevations of creatinine and urea; in 8 of these, cyclosporine levels remained in the normal range. Low MEGX values in the donors correlated with early evidence of cyclosporine toxicity (P < .0001), reduced graft function (bile output, P = .04; prothrombin time at day 5, P = .005), and prolonged stay in the intensive care (P = .022). The MEGX test is valuable and reflects the metabolic capacity of liver grafts. It can predict posttransplantation complications caused by cyclosporine toxicity, and further study would evaluate its incorporation into immunosuppressive protocols.
BACKGROUND: A small animal model of one-stage total hepatectomy is needed for the study of the consequences of fulminant liver failure and to investigate the extrahepatic metabolism of drugs metabolized by the liver. The models of hepatectomy described previously in the rat have the disadvantage of multiple stages, technical difficulty, or achievement of only an incomplete removal of the liver tissue. METHODS: A Y-shaped graft was prepared from the inferior vena cava and the left renal vein of a donor rat. A total hepatectomy was performed in a recipient rat. The graft was placed and the portorenal and lower cavocaval anastomoses were performed by means of the polyethylene cuff technique. The upper cavocaval anastomosis was fashioned with a continuous suture. The procedure was performed on 49 rats, and the animals were studied for survival and biochemical profiles. RESULTS: The surgical procedure took a mean of 40 +/- 5 minutes and was not associated with any operative deaths. The portal clamping time did not exceed 15 minutes. Spontaneous mean survival of the anhepatic rats was 360 +/- 30 minutes, and glucose supplemented animals had a mean survival time of 20 +/- 5 hours. The anhepatic state was associated with significant metabolic and biochemical alterations. CONCLUSIONS: This procedure is quick to perform and does not require considerable microsurgical expertise. It provides a reproducible small animal model of total hepatectomy that is particularly useful for metabolic studies.
OBJECTIVE: The objective of this study was to analyze the specificity of detecting liver tumor cell dissemination by alpha-fetoprotein (AFP) mRNA in peripheral blood. SUMMARY BACKGROUND DATA: Alpha-fetoprotein mRNA has been used for the detection of circulating micrometastatic tumor foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. METHODS: Sixty-four consecutive patients with malignant HCC (n = 20), liver metastases (n = 27), or nonmalignant (n = 17) liver diseases undergoing partial or total hepatectomy and orthotopic liver transplantation were included in this prospective study from January to July 1995. Peripheral blood samples were obtained before surgery, during surgery, and after surgery (range, 6-15 months). Total mRNA was extracted from nucleated cells, and cDNA synthesis and polymerase chain reaction amplification (nested polymerase chain reaction in one tube) were performed with specific AFP primers. RESULTS: Preoperative AFP mRNA was detected in 20 patients (17%), of which 5 of 20 had HCC. Intraoperative assessment showed positive AFP mRNA values in a total of 34 patients (53%) with various causes, of which 8 of 20 (40%) had HCC, 17 of 27 (63%) had other malignancies, and 9 of 17 (53%) had nonmalignant diseases. Recurrent tumor in patients with HCC occurred in four cases after surgery (range, 6-15 months) and did not correlate with AFP mRNA positivity before surgery, during surgery, or after surgery. CONCLUSIONS: Alpha-fetoprotein mRNA in peripheral blood is not a specific marker of circulating micrometastases from HCC, especially in the context of surgical treatment of HCC.
OBJECTIVE: To investigate the impact of preoperative transarterial lipiodol chemoembolization (TACE) in the management of patients undergoing liver resection or liver transplantation for hepatocellular carcinoma. PATIENTS AND METHODS: TACE was performed before surgery in 49 of 76 patients undergoing resection and in 54 of 111 patients undergoing liver transplantation. Results were retrospectively analyzed with regard to the response to treatment, the type of procedure performed, the incidence of complications, the incidence and pattern of recurrence, and survival. RESULTS: In liver resection, downstaging of the tumor by TACE (21 of 49 patients [42%]) and total necrosis (24 of 49 patients [50%]) were associated with a better disease-free survival than either no response to TACE or no TACE (downstaging, 29% vs. 10% and 11 % at 5 years, p = 0.08 and 0.10; necrosis, 22% vs. 13% and 11% at 5 years, p = 0.1 and 0.3). Five patients (10%) with previously unresectable tumors could be resected after downstaging. In liver transplantation, downstaging of tumors >3 cm (19 of 35 patients [54%]) and total necrosis (15 of 54 patients [28%]) were associated with better disease-free survival than either incomplete response to TACE or no TACE (downstaging, 71 % vs. 29% and 49% at 5 years, p = 0.01 and 0.09; necrosis, 87% vs. 47% and 60% at 5 years, p = 0.03 and 0.14). Multivariate analysis of the factors associated with response to TACE showed that downstaging occurred more frequently for tumors >5 cm. CONCLUSIONS: Downstaging or total necrosis of the tumor induced by TACE occurred in 62% of the cases and was associated with improved disease-free survival both after liver resection and transplantation. In liver resection, TACE was also useful to improve the resectability of primarily unresectable tumors. In liver transplantation, downstaging in patients with tumors >3 cm was associated with survival similar to that in patients with less extensive disease.
The molecular basis of cirrhosis, the most frequent underlying liver disease in hepatocellular carcinoma, remains unclear. We investigated microsatellite instability at six different loci on chromosomes 2p, 3p, 5q, 9p, 13q and 17p, in DNA from 38 cirrhotic livers of viral (n=28) and nonviral (n=10) origin. Sixty percent of the patients exhibited microsatellite alterations in at least one chromosome locus. A striking feature was the close association between genomic instability and cirrhosis linked to hepatitis B viral infection (P<0.01). This high instability may be a clue to the etiology of cancer induced by the hepatitis B virus.
OBJECTIVES: Patients who continue to bleed despite standard treatment including sclerotherapy have a poor prognosis with a mortality up to 90%. TIPS has been used as salvage therapy for ruptured oesophageal varices refractory to all conventional treatments. METHODS: During a period of 3 years, 65 cases of variceal rupture in cirrhotic patients were treated at our center and a salvage TIPS was performed in 15 patients (23%) for active uncontrolled hemorrhage despite standard medical and endoscopic treatment (Child A, 2; B, 1; C, 12). The procedure was technically successful in all cases and hemorrhage was controlled in 11/15 cases (73%). RESULTS: Three patients died of persistent bleeding and liver failure; one case of moderate and persistant hemorrhage was controlled by transfusions until bleeding ceased. This patient was transplanted 3 months after TIPS and is alive 3.5 years later. Two patients had early recurrence of hemorrhage due to TIPS thrombosis. These 2 cases of thrombosis were deobstructed but both patients died of liver failure despite bleeding control. Overall, 7 patients died within 60 days of TIPS by hemorrhage and/or liver failure. One patient died of liver failure 7 months after TIPS following surgery for aortic aneurysm. None of the 8 survivors after 60 days had bleeding recurrence or encephalopathy. Actuarial survival was 42.7 +/- 14% at 1 and 2 years. CONCLUSION: TIPS is currently the alternative of choice for persistant bleeding refractory to standard management. However despite control of hemorrhage, operative mortality remains high due to the underlying severe cirrhosis.
Conventional percutaneous liver biopsy in the early postoperative period, within 30 days, following liver transplantation may be impossible due to coagulopathy and/or ascites. The use of transjugular liver graft biopsy (TJLB) in this setting is an attractive alternative in that a tissue diagnosis can be obtained despite the relative contraindications for percutaneous biopsy during this period. During the early posttransplant period, 124 TJLBs were performed in 105 liver patients, the majority (89%) of whom had standard liver transplantation without preservation of the native inferior vena cava; the others (11%) had the native inferior vena cava intact. The technical success rate was 87%, with adequate specimen for definitive diagnosis in most instances (86%), which included both rejection (61%) and nonrejection (39%) diagnoses on final histopathology. The biopsy diagnosis influenced clinical management in the majority of cases (65%), with decisions made to perform retransplantation (3%), to influence initiation of antirejection therapy (59%), and to institute antiviral therapy (3%). There was no morbidity or mortality associated with TJLB and it is feasible, safe, and effective in the early period after liver transplantation.
OBJECTIVE: The authors objective is to report their experience with auxiliary partial orthotopic liver transplantation in fulminant hepatitis (FH) and to discuss the principles that may help in its safe application. SUMMARY BACKGROUND DATA: Auxiliary partial orthotopic liver transplantation is an attractive therapeutic method in FH because it provides hepatic function, whereas the remaining native liver is given the possibility to recover. Despite early encouraging reports, its place in the treatment of FH remains to be defined. METHODS: Evaluation of 5 cases of FH treated with auxiliary partial orthotopic liver transplantation from a collective of 22 transplantations for 35 cases of FH referred to the authors' center from January 1994 to November 1995. The grafts were one left lobe, two left livers, and two right livers. RESULTS: The native liver regenerated in three patients: one with Reye's syndrome who died of irreversible neurologic damage, one with FH caused by the hepatitis B virus who is alive 20 months after ABO incompatible graft removal, and one with FH caused by the hepatitis A virus who had her graft removed at 4 months. In two patients, regeneration did not occur: one with drug-induced FH who died of sepsis 3 months after surgery and one with FH of unknown origin who was retransplanted with a standard liver transplantation at 4 months for uncontrollable biliary rejection of an ABO incompatible graft (alive at 10 months). Two of the three patients who survived suffered severe neurologic complications. CONCLUSIONS: Auxiliary partial orthotopic liver transplantation is an attractive treatment for FH, especially in the presence of good prognostic factors for native liver regeneration: a young patient, rapid onset of the disease, and viral hepatitis. It should be considered cautiously in patients with advanced encephalopathy. By providing a smaller mass of liver tissue than with standard orthotopic liver transplantation, and as a more complex operative procedure, auxiliary partial orthotopic liver transplantation may not be as effective in arresting the progression of neurologic damage.
OBJECTIVE: The authors objective is to report their recent experience with split-liver transplantation, focusing on the results and the impact on organ shortage. SUMMARY BACKGROUND DATA: There is an insufficient number of organs for liver transplantation. Split-liver transplantation is a method to increase the number of grafts, but the procedure is slow to gain wide acceptance because of its complexity and the poor results reported in previous series. METHODS: During the year 1995, the authors split 20 of 83 transplantable livers allocated to the authors' center, generating 40 grafts: 23 were transplanted locally and 17 were given to partner centers. During the same period, the authors accepted four split-liver grafts proposed to them by other centers. Overall, 27 split-liver transplantations were done in the authors' unit, accounting for 30% of the 90 transplants performed in 1995. RESULTS: One-year patient and graft survival rates for split-liver transplantation were 79.4% and 78.5%, respectively. Arterial and biliary complications rates were 15% and 22%, respectively, with none leading to graft loss. Primary nonfunction occurred in one case (4%). By splitting 24 of 87 transplantable livers (4 of which were in partner units), a total of 111 transplantations were performed, increasing graft availability by 28%. CONCLUSIONS: Split-liver transplantation is achieving graft and patient survival rates similar to that of whole liver transplantation despite a higher incidence of complications, which could become less frequent as experience is gained with this procedure. A wider acceptance of split-liver transplantation could markedly increase the supply of liver grafts.
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Severe veno-occlusive (VOD) disease is a major cause of morbidity and mortality in allogeneic bone marrow transplant recipients, and new approaches in managing patients who develop serious VOD is needed. In this report, we describe a patient who underwent transjugular intrahepatic portosystemic stent-shunt (TIPS) for life-threatening VOD are following allogeneic bone marrow transplantation for AML. Although the patient died of CMV-associated pneumonitis 5 weeks later, the TIPS functioned well until her death and permitted regression of the hepatic and renal symptoms. This report suggests that TIPS may be feasible and effective for managing patients with life-threatening liver dysfunction after marrow transplantation.
The effects of administration of endotoxin to donors or recipients on the mortality rate, evolution of endotoxin levels, and tumor necrosis factor alpha (TNF-alpha) release were investigated in a syngenic orthotopic liver transplantation model in Lewis rats with portal reperfusion only. No significant recipient endotoxemia, TNF-alpha release, or mortality occurred in control recipients following transplantation from normal donors. The doses of endotoxin needed to kill 50% and 100% of animals after hepatic artery ligation were, respectively, 4 mg/kg and 10 mg/kg. Transplantation of animals' livers with no preservation phase from donors who were administered a lethal dose of endotoxin for this combination (10 mg/kg) produced significant recipient endotoxemia at 10 min (6.9 +/- 2.5 x 10(3) endotoxin unit/ml (EU/ml), P < 0.01), 45 min (8.8 +/- 1.1 x 10(3) EU/ml, P < 0.001) and 8 hr (18.5 +/- 3.5 x 10(3) EU/ml, P < 0.001) after graft reperfusion. Significant levels of TNF-alpha were also detected in these animals at 45 min (280 +/- 70 pg/ml, P < 0.007) and 8 hr (80 +/- 40 pg/ml, P < 0.05) when compared with the controls. Mortalities in recipients of OLT from donor animals that had received endotoxin (2 mg/kg or 4 mg/kg) immediately prior to the harvesting procedure was 0% and 20%, respectively, compared with no death in the control group. When recipient animals were administered endotoxin immediately after graft reperfusion the resistance to endotoxin administration was significantly reduced compared with animals that had not received OLT (LD50 < 2 mg/kg versus 4 mg/kg; LD100 4 mg/kg versus 10 mg/kg, respectively). These results show that endotoxin and its effects can be transferred from the liver graft donor to the recipient and that OLT per se reduces the recipient resistance to endotoxin with subsequent increase in mortality.
A 48-year-old woman with giant haemangioma of the liver underwent percutaneous transjugular placement of a stent in the left hepatic vein for relief of an obstruction due to the compression of the benign liver tumour. Following the procedure, paroxysmal atrial fibrillation occurred and right-sided heart failure gradually appeared. Echocardiography and cardiac catheterization demonstrated a fistula between the aortic root and the right atrium, that was confirmed on surgery.
OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality.