Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV. ' 2009 UICC

A national conference was held to better characterize the long-term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early-stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End-Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non-HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non-HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha-fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points. Liver Transpl 16:262-278,

Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.

Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1,2) and then applicable, with very little modification, to thoracic and other organs. However, the mechanism by which anti rejection treatment permits any of these grafts to be "accepted" has been an immunological enigma (3,4). We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5). Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into transplantation immunology and have encouraged the development of alternative therapeutic strategies (6). DISCOVERY OF GRAFT CHIMERISM After Liver TransplantationSuccessful transplants were long envisioned as an alien patch in a homogeneous host (Fig. 1, left). The first unequivocal evidence that whole-organ grafts in human beings become genetic composites (chimeras) was obtained in 1969 with karyotyping studies in female recipients of livers obtained from male cadaveric donors. Postoperatively, the hepatocytes and the endothelium of the major blood vessels of the grafts retained their donor sex, whereas the entire macrophage system, including the Kupffer cells, was replaced with recipient female cells (identified by their characteristic Barr bodies) within 100 days (7,8) (Fig. 1, middle). These observations attracted considerable attention at the time, primarily because of their implication that liver-based inborn errors of metabolism could be corrected permanently by liver replacement (9,10). This prediction has been met since then in nearly two dozen such heritable diseases (11). Each report of another liver-based metabolic disorder that was corrected by liver replacement added to the illusion that the composite (chimeric) structure of the hepatic allograft was a special feature of this organ.Address reprint requests to: Thomas E. Starzl, M.D., Ph.D., Department of Surgery, 3601 Fifth Avenue, 5C Falk Clinic, University of Pittsburgh, Pittsburgh, PA, 15213. NIH Public Access Author ManuscriptHepatology. Author manuscript; available in PMC 2010 October 26. Published in final edited form as:Hepatology. 1993 June ; 17(6): 1127-1152. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript After Intestinal TransplantationThe illusion of uniqueness of the hepatic graft was dispelled in 1991 with the demonstration, first in rat models (12) and then in human beings (13), that all successfully transplanted intestines also were chimeric. The epithelium of the bowel remained that of the donor, but lymphoid, dendritic and other leukocytes of recipient phenotype quickly became the dominant cells in the lamina propria, Peyer's patches and mesenteric nodes. The transformation in experimental animals and in human beings (Fig, 2) was the same whether the bowel was transplanted alone or as a part of a multivisceral gra...

SummaryBackground-Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants.