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Biomedical subjects

Myron Schwartz

Publications and source records attributed to Myron Schwartz.

29 records · Page 2Linked to original sources

The incidence and significance of late acute cellular rejection (>1000 days) after liver transplantation.

Acute cellular rejection (ACR) after liver transplantation occurs in as much as 70% of patients within the first year. There is very little known about ACR that occurs more than 1 yr after transplant, and it is generally believed that late occurring ACR may be more resistant to medical treatment and is associated with a higher rate of chronic ductopenic rejection and graft loss. A total of 532 recipients with more than 1000 d follow-up and who did not have hepatitis C were identified. Forty-three (8.1%) had biopsy proven late ACR at a mean of 1545 +/- 441 d post-transplant. Additionally, 38 of the 43 (88.4%) patients with late ACR had earlier episodes of ACR before 1000 d post-transplant vs. only 295 of the 488 patients (60.5%) that did not have late ACR (p < 0.01). The incidence of primary sclerosing cholangitis (PSC) was 32.6% among patients with late ACR and 11.1% among patients without late ACR (p < 0.01). The overall patient survival for patients who had late ACR (n = 43) is 81.4% while for patients without late ACR (n = 488) it is 82.0% (p = ns). Patients remain at risk for ACR even after 1000 d post-transplant, particularly those with PSC.

Acute Disease↗

Unresectable squamous cell carcinoma of donor origin treated with immunosuppression withdrawal and liver retransplantation.

Posttransplantation allograft malignancy of donor origin is a rare complication after liver transplantation. In the case described, subjective fevers and nonspecific abdominal complaints nearly 6 months following cadaveric liver transplantation in a young woman prompted an evaluation which was remarkable for a large central liver mass. A poorly differentiated squamous cell carcinoma was diagnosed, but was unresectable at exploration. The tumor was confined to the liver. Histocompatibility testing using polymerase chain reaction (PCR) amplification techniques identified both donor and recipient HLA alleles. The patient was treated with chemoembolization, systemic chemotherapy and cessation of immunosuppression. Repeat biopsy 2 months later showed the tumor to be completely necrotic. With decompensated liver disease, she was relisted and retransplanted. More than 2 years later she remains disease-free with complete pathological remission. This is the only reported case of squamous cell carcinoma of donor origin arising in a transplanted liver.

Adult↗

Liver transplantation for hepatocellular carcinoma.

Because hepatocellular carcinoma (HCC) arises in cirrhotic livers and is often multifocal, transplantation seems to be a rational approach. Early results were poor, but current restrictive selection criteria can yield excellent results. Patients with 1 HCC nodule </=5 cm in diameter, or 2-3 nodules </=3cm, receive United Network Organ Sharing priority; nevertheless, dropout from the waiting list is common. Predictors of dropout include multiple tumors and tumors with a diameter >3 cm. Nonsurgical methods are commonly used to prevent tumor progression and thus prevent dropout. Expanding selection criteria results in more patients with HCC being cured at the expense of a higher incidence of recurrence. Molecular/biologic information is beginning to be incorporated into current staging systems in order to better predict HCC recurrence. In considering liver transplantation, the impact of the underlying liver disease is an important consideration; recurrent hepatitis C after transplant lowers patient survival independent of tumor recurrence.

Carcinoma, Hepatocellular↗

Influenza vaccination in orthotopic liver transplant recipients: absence of post administration ALT elevation.

Influenza vaccination has reduced life-threatening complications from influenza virus infection in adult liver transplant recipients. We evaluated changes in aminotransferase level and immunogenicity of influenza vaccination in liver transplant recipients. Fifty-one liver transplant recipients were administered a standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT values were measured at baseline, 1 week and 4-6 weeks postvaccination. Antibody responses to each component of the vaccine were measured at baseline and after 4-6 weeks by a hemagglutination inhibition (HAI) assay. Response was defined as an HAI titer > or = 1: 40 and/or a 4-fold increase in antibody titers from baseline. An ALT elevation was defined as a rise of > or = 50% from baseline. There was no difference in the median rise in ALT value between seroconverters and nonseroconverters. A significant number of recipients developed potentially protective antibody titers (p-value < 0.0001). At less than 4 months post transplantation, 1/7 (14%), at 4-12 months, 6/9 (67%), and after 12 months, 30/35 (86%) subjects responded to the H1 strain. Of 51 recipients, one HCV (-) recipients vaccinated within 3 months of transplantation developed acute cellular rejection. Influenza virus vaccination is not associated with allograft rejection or ALT flares in liver transplant recipients.

Adult↗

Epstein-Barr virus and human hepatocellular carcinoma.

Recent studies suggest that Epstein-Barr virus (EBV) may act as a helper virus for the development of hepatocellular carcinoma by promoting replication of the hepatitis C virus (HCV) in the infected liver. Detection of EBV DNA in a high percentage of HCV-positive human hepatocellular carcinomas (HCC) from Japanese patients has supported this concept. In order to determine whether EBV infection is associated with HCC, we examined paraffin-embedded tissues from 31 cases of non-cirrhotic livers with hepatocellular carcinoma for the presence of EBV, HCV and hepatitis B virus (HBV) infection. RNA prepared from tumor samples were used as a template for reverse transcription followed by double-nested PCR with primers for the 5' untranslated region (NT) of HCV. DNA extracts of tumor samples were tested by single polymerase chain reaction for the detection of EBV and HBV (X- and/or S-gene) DNA sequences. To control for nucleic acid integrity, all tumor samples were amplified for human beta-globin DNA by polymerase chain reaction and subjected to Southern blot hybridization. None of the cases was found to be positive for EBV. Ten HCC cases (32%) tested positive for HCV and 12 HCC cases (38%) tested positive for HBV. Six of the surveyed patients had nucleic acids of both HCV and HBV in their tumor tissue. All HCC tumor samples were positive for beta-globin. Our study shows that HCV and HBV infections, but not EBV infection, are associated with hepatocarcinogenesis in non-cirrhotic livers. Other unknown risk factors seem to be in effect in the development of hepatocellular carcinoma in non-cirrhotic livers.

Blotting, Southern↗

Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status.

OBJECTIVES: The incidence of hepatocellular carcinoma (HCC) seems to be rising in the United States (US), and considerable variability in the incidence and etiology of HCC has been noted among different racial and ethnic groups in this country. The aim of this study was to evaluate the influence of racial and ethnic status in the viral etiology of HCC in the US. METHODS: Retrospective surveys were conducted at liver transplantation centers in the US. Respondents were asked to review the charts of all patients with HCC seen at their institution for the 2-yr period between July, 1997, and June, 1999, and provide information about the racial and ethnic distribution of cases and their serological status with regard to hepatitis B and C markers. RESULTS: Complete information was available on 691 patients who formed the basis of this study, comprising 59% whites, 14% blacks, 16% Asians, and 11% other racial groups. Of the patients, 107 patients (15.4%) were positive for hepatitis B surface antigen (HBsAg), 322 had antibodies to hepatitis C virus (anti-HCV) (46.5%), 33 (4.7%) had both HBsAg and anti-HCV), and 229 (33.1%) had neither marker present. Clear differences were seen among racial groups. Anti-HCV positivity was the most frequent risk factor in both blacks and whites, whereas HBsAg positivity was the most frequent etiological factor in Asians with HCC. CONCLUSIONS: HCV infection seems to be the major risk factor for HCC in the US, particularly among individuals of white and black ethnicity, whereas hepatitis B remains the main risk factor among patients of Asian ethnicity. These preliminary findings indicate the need for a more detailed study of ethnic variability in the pathogenesis of HCC.

Adult↗

Candidate selection criteria for living donor liver transplantation.

Living donor liver transplantation is a new surgical technique that challenges the assumptions of the current system for allocation of livers for transplantation. Arguments based on justice in the setting of scarcity, and the consequent need for triage, do not apply. The risk to the living donor, an order of magnitude higher than that for kidney donation, raises different ethical concerns related to autonomy, what constitutes an acceptable risk-benefit equation, and who is to decide.

Humans↗

Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials.

Hepatocellular carcinoma (HCC) is common worldwide, and its incidence is increasing. Liver resection or transplantation is potentially curative, although subsequent recurrence and death are common. We reviewed randomised trials on the role of adjuvant therapy in resectable HCC. We identified 13 randomised trials with recurrence or survival endpoints reported at 3 years or longer. Three studies involved predominantly systemic adjuvant chemotherapy; four involved predominantly hepatic-artery-based chemotherapy or embolisation; and six used other therapeutic modalities including immunological, radiation, and differentiation agents. A therapeutic benefit in terms of disease-free or overall survival was noted in six trials, five of which involved modalities other than systemic or hepatic-artery chemotherapy or embolisation. We conclude that systemic and hepatic-artery chemotherapy or chemoembolisation have not been shown to improve overall or disease-free survival after resection of HCC, although there has been no definitive trial comparing adjuvant systemic chemotherapy with no treatment. Other adjuvant modalities (mostly tested in small, preliminary settings) may confer benefit after potentially curative resection of HCC.

Carcinoma, Hepatocellular↗

Hand-assisted laparoscopic donor hepatectomy for living related transplantation in the porcine model.

Use of a minimally invasive approach for donor nephrectomy has proven to be safe and feasible and has increased the pool of donors for living related renal transplantation. A porcine study to assess the safety and feasibility of performing laparoscopic donor hepatectomy was performed, with potential application to human liver donors for living related liver transplantation. Of the 10 50-kg pigs used, 2 underwent an open left lateral segmentectomy to define the pig anatomy. Two subsequent pigs underwent a laparoscopic liver resection to refine the technique. Subsequently, under sterile conditions, six pigs underwent laparoscopic liver resection with use of a hand-assisted technique for long-term study. Diameters and lengths of hepatic vessels and ducts were measured. Operative blood loss, operative time, and warm ischemia duration were noted. Biopsies of the resected specimens were done to look for ischemia. There was one operative death in the group with chronic liver failure, due to stapler misfire and hemorrhage from the left hepatic vein. The only instance of morbidity was a wound infection. The resected liver had minimal warm ischemia time and microscopic changes, which led us to believe that the organ was suitable for transplantation. We believe that this long-term study establishes the feasibility of this procedure.

Alanine Transaminase↗

Adult-adult living donor liver transplantation.

After the first report from Denver in 1998 of a successful liver transplant in an adult using the right lobe from a living donor, the procedure was rapidly adopted by many transplant centers as a potential solution to the critical shortage of donor livers. By the end of 2000, when the National Institutes of Health held a Consensus Conference on Adult-Adult Living Donor Transplantation (AALDT), a substantial body of literature had already developed and many of the associated technical and medical pitfalls had been defined. The exponential expansion of the procedure came to a dramatic halt in January 2002 when the death of a donor occurred at Mount Sinai Hospital--the busiest AALDT center in the United States. This led to a widespread reassessment of the risks inherent in right lobe donation. Yet, the problem that drove the development of this controversial technique--the dire shortage of organs for transplantation--still persists. After a 50% drop in the number of AALDT procedures performed in the United States in 2002 compared with 2001, centers are regrouping and approaching AALDT with renewed interest, albeit with heightened awareness of the attendant risks. On November 2, 2002, a state-of-the-art symposium on AALDT was held in Boston, MA, under the combined auspices of the American Hepatico-Pancreato-Biliary Association and the American Association for the Study of Liver Diseases. This article comprises the presentations at the symposium on three subjects of critical importance concerning AALDT. These include advances in surgical technique, candidate selection, and hepatic regeneration; each subject is acknowledged by an expert in the field.

Adult↗