Liver transplantation for primary and metastatic hepatic malignancy: a single center experience.
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Cause of Death↗
Biomedical subjects
Mark J Thomas
Publications and source records attributed to Mark J Thomas.
Malignancy in pediatric transplant recipients.
Malignancy is a well defined complication of chronic immunosuppression. Post transplant malignancies appear to be related to cumulative doses of immunosuppression, and in pediatric patients, acute infection of previously naive patients. The most commonly encountered malignancy in this age population is Post Transplant Lymphoproliferative Disorder (PTLD). PTLD is not a single entity but rather represents a continuum of disease. Treatment of PTLD should be initiated with immunosuppression reduction. Standard dose chemotherapy leads to significant morbidity. With the introduction of anti-CD20 antibody treatment with rituximab, chemotherapy has become second line therapy. The occurrence of solid malignancy appears to be associated with chronic immunosuppression. These cancers include those of skin, gynecologic organs, and the rectum, all of which appear to have the strongest association with viral mediators. Several strategies have been postulated to minimize the occurrence of malignancy. These include ganciclovir prophylaxis for the prevention of PTLD and the use of mychophenolic acid and TOR inhibitor maintenance to diminish the incidence of PTLD and solid malignancies. This leaves transplant physicians with several new and novel immunosuppressive agents with uncertain oncologic potentials that will need to be examined over the next decade.
Adolescent↗
An initial experience and evolution of laparoscopic hepatic resectional surgery.
BACKGROUND: The use of minimally invasive procedures has revolutionized modern surgery. Only recently has laparoscopy been introduced for use in hepatic surgery. METHODS: Patient demographics, tumor characteristics, and outcomes were evaluated for all initial cases of laparoscopic hepatic resection. RESULTS: Twenty-one resections were performed in 17 patients; 5 were performed for malignancy, of which 3 had underlying cirrhosis, and the remaining 12 for benign symptomatic disease. Mean patient age was 55.4 (range, 24-82 years). The mean number of lesions was 1.4 (range, 1-5), having an average size of 7.6 cm (range, 2-30 cm). Mean operative time was 2.8 hours (range, 2-5 hours) hours. Most resections involved 1 or more Couinaud segments. Mean blood loss was 288 cc (range, 50-150 cc). Complications included re-operation for hemorrhage (n=2), biliary leakage (n=1), and death from hepatic failure (n=1). Mean length of stay was 2.9 days (range, 1-14). When compared with our series of 100 patients who underwent open hepatic resection for benign tumors, significantly greater means ( P <.05) were noted for blood loss (485 cc), operative time (4.5 hours), and length of stay (6.5 days). CONCLUSIONS: Laparoscopic hepatic surgery, though complex, can be performed safely and efficaciously. Minimally invasive surgery appears to provide several distinct advantages over traditional open hepatic surgery. However, techniques for the laparoscopic control of bleeding and bile leak remain in their infancy.
Adult↗
Morphine-induced c-fos mRNA expression in striatofugal circuits: modulation by dose, environmental context, and drug history.
Opiates and psychostimulants produce many shared behavioral and neurobiological adaptations, such as behavioral sensitization and the induction of immediate early genes in the caudate-putamen (CPu). Previous studies indicate that factors such as dose, the environmental context surrounding drug administration and drug history can influence both morphine- and psychostimulant-induced behavioral sensitization. In addition, these factors can modulate the ability of psychostimulants to engage striatofugal circuits in the CPu. The present study, therefore, sought to examine whether these factors have similar influences over the ability of morphine to engage cortico-striatofugal circuits. We report that, when given in the home cage, morphine produced a small, but significant increase in the number of c-fos+ striatonigral cells and c-fos+ cells in cingulate cortex, but had no effect on the number of c-fos+ striatopallidal cells. When given in a novel test environment, however, morphine dramatically increased the number of c-fos+ striatonigral cells in a dose-dependent fashion, and this effect was maintained following repeated treatment. Unexpectedly, morphine treatment in a novel environment produced a dose-dependent reduction in the number of c-fos+ striatopallidal cells and c-fos+ cells in cingulate cortex, relative to exposure to novelty alone-effects that were reversed by repeated morphine treatment. We suggest that alterations in c-fos expression patterns in striatofugal circuits following morphine administration may be involved in drug-experience-dependent plasticity.
Analgesics, Opioid↗
Synaptic plasticity in the mesolimbic dopamine system.
Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.
Animals↗
Pretransplant MELD score as a predictor of outcome after liver transplantation for chronic hepatitis C.
The Model of End-Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post-transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty-seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15-24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12 months were significantly lower in the higher MELD score groups, as was patient survival at 24 months (p-values, 0.01-0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1 year post-transplant was significantly lower with higher MELD scores (p = 0.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post-transplant graft injury in these patients should be explored.
Adult↗
A correlation between the pretransplantation MELD score and mortality in the first two years after liver transplantation.
The Model for End-Stage Liver Disease (MELD) score is now the criteria for allocation in liver transplantation for patients with chronic disease. Although the score has been effective in the prediction of mortality in patients awaiting liver transplantation, its abilities to predict posttransplantation outcome need study. The aim of this study is to compare outcome in the first 2 years after liver transplantation according to the pretransplantation MELD score. The study includes 669 consecutive patients who underwent primary liver transplantation between December 1993 and October 1999 in a single transplant center. Patients who died of malignancy were excluded from the series. Pretransplantation MELD score was calculated using the United Network for Organ Sharing formula. Patients were stratified according to MELD score less than 15, 15 to 24, and 25 and higher. Posttransplantation survival at 3, 6, 12, 18, and 24 months was significantly lower in the groups with a higher MELD score. The difference was significant for hepatitis C and noncholestatic liver diseases, but not cholestatic diseases. In patients with a MELD score between 15 and 24, survival was significantly greater with cholestatic diseases and lower in patients with hepatitis C. In our study, pretransplantation MELD score correlates with survival in the first 2 years after transplantation. There is a survival advantage for patients with cholestatic diseases compared with those with hepatitis C. These findings suggest the need to readjust MELD score-based allocation decisions to consider patient outcome.
Adolescent↗