Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas-kidney transplants.
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Biomedical subjects
Publications and source records attributed to D Forti.
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BACKGROUND/AIMS: Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. METHOD: Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. RESULTS: Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. CONCLUSIONS: These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.
BACKGROUND/AIMS: Liver transplantation for endstage liver cirrhosis provides a useful model to investigate the pathogenetic role of hepatotropic viral agents. Recently, a new member of the Flaviviridae family, provisionally named HGV/GBV-C virus, has been associated with acute and chronic non A-E hepatitis. We studied 136 patients with cirrhosis consecutively transplanted at our institution for evidence of hepatitis G virus infection and correlation with the patients' clinical course. METHODS: All patients survived for at least 6 months after transplantation (median follow-up 44 months) and underwent routine liver biopsies. Hepatitis G virus infection was studied using both direct viral RNA identification by RT-PCR and indirect detection of antibodies to the E2 glycoprotein. RESULTS: There was a high frequency of the hepatitis G virus among patients undergoing liver transplantation, with HGV RNA and anti-E2 prevalence rates of 18.4% and 26.5%, respectively. HGV RNA prevalences significantly increased after transplantation (47.8%), with 47.3% rate of new infections in susceptible subjects. Anti-E2 antibodies were significantly more prevalent among patients transplanted for HCV-related cirrhosis and represented a strong protective factor against hepatitis G virus reinfection or recurrent infection. No correlation was found between HGV RNA or anti-E2 prevalences and survival after transplantation or rates of recurrent liver damage. CONCLUSIONS: All available evidence suggests that, although liver transplant patients are heavily exposed to hepatitis G virus both before and after transplantation, hepatitis G virus does not induce liver disease in this setting. Most infections appear to be self-limited and induce a protective immunity which is marked by the presence of anti-E2 antibodies.
UNLABELLED: Focal nodular hyperplasia (FNH) and adenoma are rare benign hepatic tumors, and the standards for diagnosis and treatment still remain controversial. Usually adenoma is an indication for resection, due to its tendency to bleed and to degenerate; FNH, on the contrary, may be treated conservatively. Preoperation differential diagnosis is, however, difficult, often impossible. MATERIALS AND METHODS: Thirty-eight patients with presumed hepatic adenoma and/or FNH were studied at our department from 1984 to 1996. Preoperative assessment included clinical evaluation and symptoms, laboratory tests, liver biopsy, ultrasound scan, computed tomography scan, magnetic resonance imaging, scintigraphy, and angiography. Thirteen patients had a presumed diagnosis of FNH, 16 of adenoma, and 9 of undetermined benign lesions; 27 had hepatic resections (3 with laparoscopic technique), and 11 were not operated on and are actually under a strict follow-up observation. RESULTS: The final diagnosis was 19 FNH and 19 adenomas (2 of which contained areas of hepatocarcinoma). Presumed diagnosis was confirmed in 71% of cases. Use of oral contraceptives, abdominal symptoms, and pathologic liver test results were frequent in patients with adenomas. There were no deaths after surgery. All resected patients were tumor free during the follow-up, and in 10 of the 11 nonoperated cases, the size of the nodules remained unchanged. We conclude that precise diagnosis of these benign liver tumors remains difficult and sometimes impossible, despite new imaging techniques. Hepatic resections can be performed under very safe conditions; laparoscopic surgery may play a role in selected cases. Adenomas and uncertain cases are clear indications for surgery. Only when a diagnosis of FNH can be firmly confirmed in asymptomatic patients is strict observation without surgery recommended.
A partial modification of the standard end-to-side anastomosis usually performed in heterotopic vascularized organ transplantation in the rat is described. Use of the method completely abolished the approximately 20% severe post-declamping bleeding due to gaps in those blind areas, the stitching of which are at risk using previously described methods. The authors thus recommend the method for performing heart, kidney, pancreas and small bowel transplantations in the rat.
Several genotypes of hepatitis C virus (HCV) have been recently identified by phylogenetic analysis, but their clinical relevance in the liver transplant setting is unknown. We evaluated the incidence and course of recurrent hepatitis C after transplantation in 50 patients who underwent transplantation for HCV-related liver disease. Liver biopsy specimens were obtained when clinically indicated and at yearly intervals; hepatitis was histologically graded and staged according to standard criteria. HCV-RNA was detected by nested reverse-transcription polymerase chain reaction (RT-PCR). HCV genotyping was performed by primer specific PCR. Follow-up was 6 to 62 months. HCV genotype distribution after transplantation of our 50 patients was as follows: 31 type 1b, 13 type 2a, 3 type 1a, 1 type 3a, 1 type 1b/2a, and 1, undetermined. Actuarial rates of recurrent hepatitis and of severe fibrosis or cirrhosis 5 years after transplantation were 56% and 20%, respectively, in patients infected by type 1b and 33% (P = .18) and 8% (P = .16) in those infected by 2a. In conclusion, this study provides evidence that in patients infected by HCV type 1b there is a trend for a more aggressive recurrent liver disease.
Defibrotide (a polydeoxyribonucleotide) and oligotide (an oligodeoxyribonucleotide) obtained from mammalian single-stranded DNA, have been demonstrated to have anti-ischemic activity in some experimental models of ischemia/reperfusion of kidney in rats. We hypothesized that their anti-ischemic activity could be related to an inhibition of leukocyte-endothelial cell adhesion and also the consequent generation of oxygen free radicals by leukocytes. We studied the in vitro adhesion of neutrophils to human umbilical vein endothelial cells under basal conditions and following neutrophil or endothelial cell activation (using 10(-7) fMLP and 500 U/ml TNF-alpha, respectively). Defibrotide and oligotide significantly inhibited neutrophil adhesion to endothelial cells (after only 1 min of drug treatment). When the anti-LFA-1 70H12 F(ab)2 monoclonal antibody was used, the drugs exerted only slight additional inhibition of the adhesion of fMLP-activated neutrophils to endothelium. These results, confirmed in NIH/3T3-ICAM-1-transfected cells, demonstrate that defibrotide and oligotide interfere with leukocyte adhesion to endothelial cells by an LFA-1-dependent mechanism.
Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoembolization was performed on 25 patients. The perioperative mortality rate was 27% (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94%, 76%, 76%, and 83%, 75%, 75%, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for unresectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.
A discrepancy exists worldwide between the number of suitable liver donors and the increasing demand for transplantation. Thus many centers have considered widening their liver donor acceptance criteria and this may increase the incidence of primary dysfunction (PD) with negative effect on the results of transplantation. In order to reduce the incidence of PD and improve patient and graft survival it becomes important to identify those risk factors associated with its occurrence. In a retrospective univariate and multivariate analysis we evaluated several donor, preservation and recipient parameters and their correlation with PD. In our Department 282 orthotopic liver transplantations (OLT) were performed on 256 adult patients over a 10-year period. Excluded were 15 cases with early vascular problems and 4 intraoperative deaths. A complete series of donor, recipient and procedure-related data were analyzed. About 30% of donors showed abnormal values. In 70 cases of PD (26%) there was a 61.4% graft failure rate compared with 15% in the group with immediate function (P < 0.05). Univariate analysis showed donor age, steatosis, ischemia time, amines, oliguria, hypotension and ICU stay to be significantly associated with PD. Multivariate analysis showed steatosis, ischemia time and amine dosage to be independent risk factors for the development of primary non function. In conclusion, the acceptance of marginal donors worsened the results of transplantation, but the rejection of these donors would reduce by about 30% our transplant activity resulting in increased mortality in the waiting list. Combinations of risk factors when possible should be avoided, and ischemia time, as the only variable that can be controlled, should be kept as short as possible.
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Between January 1984 and June 1993, we treated 120 contusions of the liver in a situation of polytrauma. There were 24 patients in Stage I, 47 in Stage II, 22 in Stage III, 13 in Stage IV and 14 in Stage V according to the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma. A total of 107 patients were operated. Polytrauma related mortality was high. Besides the gravity of the liver lesion, prognosis was a function of other associated intra or extra abdominal lesions. In our series, other associated lesions were the cause fo death in 26 patients (64%) and 15 deaths (36%) were directly related to the hepatic lesion. The gravity of the Stage V lesions was related both to the state of shock of operation and the difficulties in reestablishing haemostasis. Packing decreased the effect of hypovolaemia and coagulopathy. The prognosis of supra hepatic venous lesions and hepatic resections remain disastrous. Our surgical schema has changed towards more conservative surgery and, when haemodynamic stability has been achieved, to abstention and careful monitoring. Different extra-hepatic trauma causing damage to other organs directly compromises simple hepatic lesions. The result of our series confirms the correlation between mortality and the gravity of the polytrauma as evaluated according to the Injury Severity Score proposed by Baker.
The Actinobacillus actinomycetemcomitans leukotoxin was localized in A. actinomycetemcomitans bacteria using an electron immunocytochemical thin-section labeling method. An immuno-dot blot procedure was initially used to ascertain the optimal specimen fixation. This consisted of a periodate-lysine-paraformaldehyde (2%) fixative in a phosphate buffer followed by embedding in LR White. Affinity-purified toxin was used to produce a monospecific polyclonal antibody. The reaction sites were visualized with a colloidal gold-tagged reporter antibody. The leukotoxin was found to be localized either in the cell envelope and/or in membranous vesicles on the outer surface of the bacterial cell. These results support previous observations indicating the same location.
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