Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis

BACKGROUND: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis. METHODS: Recipients of first hepatic transplants from donors with antibodies to HBV were identified retrospectively. All patients who had serology suggestive of active HBV and were negative for hepatitis C and D were included in the analysis. The Kaplan-Meier method was used to assess the actuarial recurrence-free survival on patients with graft survival longer than 1.5 months. The stepwise Cox regression model was used to identify independent predictors of HBV recurrence. RESULTS: One thousand seven hundred seventeen first liver transplants were performed at the Thomas E. Starzl Transplantation Institute from September 1, 1990, to December 31, 1999. HBV was the cause of cirrhosis in 112 patients (6.5%). Thirty-three patients had coexistent viral infection (23 HCV and 10 HDV). Fourteen donors (17.2%) were positive for HBV markers, with nine anti-HBc+ and with five both anti-HBc+ and anti-HB surface-positive; of these, 13 anti-HBc+ organ recipients had long-term survival. Nine (69.2%) of these cases were reinfected versus 20 (35.7%) in the group that received grafts from HBV- donors (P<0.05, Fisher's exact test). The mean time to reinfection was shorter in the anti-HBc+ group (2.9 yr vs. 6.4 yr, P<0.005). There were no statistical differences in graft or patient survival between the two groups. HBV prophylaxis with combined lamivudine and hepatitis B immunoglobulin (HBIG) significantly reduced the reinfection rate (P<0.03). Hepatitis Be (Hbe) antigen-positive recipients trended to faster reinfection (not significant). Cox regression analysis revealed that both anti-HBc graft donor status (RR, 2.796; P=0.020) and combination of lamivudine/HBIG (RR, 0.249; P=0.021) are independently associated with reinfection. CONCLUSIONS: The use of anti-HBc+ liver grafts does not affect graft or patient survival. However, patients who receive these organs are 2.5 times more likely to develop HBV recurrence. Lamivudine and HBIG combination decreases HBV recurrence 4-fold.     

Is 100% beating heart coronary by-pass justified?

Coronary by-pass on a beating heart may provide a safer form of surgical revascularization by avoiding the well-documented side effects of cardiopulmonary by-pass. In addition, off-pump bypass is suggested to be a good alternative to on-pump especially in high risk patients. This study reviews the feasibility of coronary by-pass on the beating heart in all patients referred to surgery. Two hundred and ninety-four patients operated on the beating heart were prospectively followed and compared to the control group of 100 consecutive patients operated with the conventional method. There were no significant differences between the groups with respect to risk factors, except the incidence of chronic obstructive pulmonary disease and ejection fraction which were higher in the conventional group, whereas peripheral vascular disease was higher in the beating heart group. There was more distal anastomosis in the conventional group. Postoperative inotrope requirement, peak creatine phosphokinase- MB, ventilation time, blood loss in the first 24 h, transfusion needs, new atrial fibrillation and length of hospital stay were significantly lower in the beating heart operations. However, there were no significant differences between the groups in terms of neurological complications, chest infection, intraaortic balloon pump usage and mortality. In conclusion, multivessel off pump coronary by-pass is feasible with the same or better results as it is observed in the conventional technique when postoperative bleeding, neurogenic complications, arrythmias, hospital stay, overall morbidity and mortality are compared.     

Vascular Targeting and Therapeutics for Squamous Cell Carcinoma of the Head and Neck

Close to 38 500 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. Traditional therapy for SCCHN has involved a multimodality approach of radiotherapy, surgery, and chemotherapy. More recently, novel therapeutic targets for solid tumors, including SCCHN, have been subject to preclinical and clinical applications. One of these newer approaches is antiangiogenic therapy. The mechanism of angiogenesis and the role it plays in tumor growth has been the subject of extensive investigation over the last 3 decades. As new antiangiogenic agents are being approved for the treatment of various solid tumors this critical review, using current preclinical and clinical evidence available thus far, examines the possible future role this new modality will have in the management of SCCHN. The different steps of angiogenesis and the corresponding targets are discussed, with a focus on vascular endothelial growth factor, as well as the preclinical and clinical evidence for the role of angiogenesis in SCCHN.     

Management of Wilms' tumor with intracardiac extension

 We review our experience and the literature in treating 4 patients with Wilms' tumor (WT) with intracardiac extension among 92 patients with this neoplasm. Cardiopulmonary bypass with circulatory arrest and profound hypothermia was used. There were 3 boys (3 years, 4 years 5 months, and 15 years) and 1 girl (6 years). The follow-up periods were 8 months, 3 years, 2 years 6 months, and 15 years, respectively. We had no surgical complications and conclude that the preoperative diagnosis is extremely important. These patients must be transferred to institutions where concomitant cardiac procedures can be performed. In treating patients with WT, Doppler ultrasound must be used preoperatively in all cases, not only those in which clinical and radiologic signs of intravascular involvement are found. We propose that preoperative chemotherapy should be used, as it shrinks the thrombus and causes desirable adherence of the thrombus to the venous wall, reducing the probability of thromboembolism during the surgical procedure. We also find this method safer than in our 1st case, where neither cardiac arrest nor hypothermia was used. Our results agree with the literature that intracardiac extension of WT does not worsen its prognosis when a rational surgical approach is used. Accepted: 26 August 1999     

A temporal comparison of post-burn rebound hyperopsonaemia with endocrine parameters

The relationship between reticuloendothelial function, as indirectly assessed by immunoreactive plasma opsonic α₂ surface binding (SB) glycoprotein levels, and alterations in the metabolic and endocrine environment were investigated following a thermal injury of between 26 and 28 per cent of the body surface area in rats. The experimental protocol was specifically designed to focus on those changes occurring in the later post-burn period as opposed to the acute phase where opsonic deficiency has been previously documented. Blood samples obtained at 1, 3, 5 and 7 days post burn manifested immunoreactive plasma opsonin levels which were 350, 50, 350 and 100 per cent higher, respectively, than concurrent control values. Plasma glucose was elevated 35 per cent on day 1, then gradually fell to 27 per cent below control levels on day 5 and returned to control values on day 7. Plasma insulin concentration was elevated 279 per cent and plasma glucagon was 106 per cent higher than control levels on day 1. However, no differences were observed at later intervals. Plasma corticosterone was elevated 369 per cent on day 1, but returned to normal by day 5. Although the present study indicates an absence of a direct temporal relationship between circulating immunoreactive opsonin and plasma levels of glucose, insulin, glucagon and corticosterone following thermal injury, an indirect (delayed) temporal relationship may be manifested during the prolonged post-burn period.     

Interferon alpha therapy for patients with essential thrombocythemia: final results of a phase II study initiated in 1986

BACKGROUND: In 1986, a Phase II trial of recombinant interferon-alpha (IFN-alpha) was initiated as therapy for patients with essential thrombocythemia (ET). METHODS: Patients were treated with subcutaneous IFN-alpha at a dose of 5 x 10(6) units/m(2) daily. In responding patients, the therapy lasted at least 3 years. RESULTS: Twenty-three patients (14 females and 9 males; median age, 41 years; age range, 20-63 years) with a median platelet count of 1350 x 10(9)/L were treated. After a median follow-up of 174 months (14.5 years), 15 of 20 evaluable patients (75%) responded, including 14 patients who achieved a complete hematologic response (CHR) (6 of them with bone marrow remission) and 1 patient who demonstrated a partial response. The median time to response was 6 months (range, 0.5-36 months), and the median response duration was 48 months (range, 5-114 months). Seven patients who achieved a CHR and were taken off therapy after they completed 3 years of maintenance therapy sustained their response for a median of 28 months. No symptoms or signs of thrombosis or hemorrhage were observed in responding patients. Eleven of 14 patients (78%) who achieved a CHR developed a recurrence, and 2 of 5 patients with recurrences who were rechallenged with IFN-alpha achieved a second response. The treatment was tolerated relatively well. CONCLUSIONS: IFN-alpha was safe and effective therapy for patients with ET, and the ability of IFN-alpha to reverse disease pathology and possibly modify the clinical course of patients with ET warrants its investigation in larger, prospective trials.