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In 1999, the Institute of Medicine suggested that instituting a continuous disease severity score that de-emphasizes waiting time could improve the allocation of cadaveric livers for transplantation. This report describes the development and initial implementation of this new plan. The goal was to develop a continuous disease severity scale that uses objective, readily available variables to predict mortality risk in patients with end-stage liver disease and reduce the emphasis on waiting time. Mechanisms were also developed for inclusion of good transplant candidates who do not have high risk of death but for whom transplantation may be urgent. The Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage Liver Disease (PELD) scores were selected as the basis for the new allocation policy because of their high degree of accuracy for predicting death in patients having a variety of liver disease etiologies and across a broad spectrum of liver disease severity. Except for the most urgent patients, all patients will be ranked continuously under the new policy by their MELD/PELD score. Waiting time is used only to prioritize patients with identical MELD/PELD scores. Patients who are not well served by the MELD/PELD scores can be prioritized through a regionalized peer review system. This new liver allocation plan is based on more objective, verifiable measures of disease severity with minimal emphasis on waiting time. Application of such risk models provides an evidenced-based approach on which to base further refinements and improve the model. (Liver Transpl2002;8:851-858.)

Laparoscopic donor nephrectomy is associated with a briefer, less intense, and more complete convalescence compared with the open surgical approach.

It is well established that exposure to solar UVB (290-320 nm) gives rise to mutations in oncogenes and tumor suppressor genes that initiate the molecular cascade toward skin cancer. Although UVA (320-400 nm) has also been implicated in multistage photocarcinogenesis, its potential contribution to sunlight mutagenesis remains poorly characterized. We have determined the DNA sequence specificity of mutations induced by UVB (A > 290 nm) The alarming rise in the frequency of skin cancer in human populations is often blamed on depletion of stratospheric ozone and the concomitant increase in environmental levels of highly genotoxic UVB (290-320 nm) in sunlight (1). Much less attention has focused on the potential contribution of solar UVA (320-400 nm), which is not absorbed by ozone and is orders of magnitude less deleterious to DNA than UVB on the basis of incident energy (2). However, UVA is mutagenic in cultured cells (3) and a complete carcinogen in rodents (4).Relative to UVB, it comprises a substantially larger proportion of the total energy in sunlight (2) and is much more efficient in penetrating the actively dividing basal layer of the epidermis (5), where photocarcinogenesis is most likely initiated through mutations. In addition, notwithstanding the very recent availability of broad-band (UVB plus UVA) sunscreens, the previous widespread use of UVB-specific blocking agents allowed greatly prolonged periods of recreational suntanning, accompanied by dramatic increases in human exposure to UVA. These considerations collectively argue that the mutagenic effects of UVA, in addition to those of UVB, may have contributed substantially to the increased incidence of skin cancer over the past number of decades.The precise identification of DNA sequence alterations induced by environmental carcinogens in cultured cells constitutes a powerful approach for probing the genotoxic basis of multistage carcinogenesis in humans (6) as well as fundamental mechanisms of mutagenesis (7). Such investigations have indicated that dipyrimidine photoproducts-i.e., cyclobutane pyrimidine dimers (CPDs) and/or pyrimidine-pyrimidone(6-4) photoproducts-are the major premutagenic lesions in cells irradiated with UVC or UVB and preferentially target C --T and some tandem CC -> TT events at dipyrimidine sites (8)(9)(10)(11)(12)(13)(14). It was subsequently shown that mutated p53 tumor suppressor genes frequently recovered from human basal and squamous cell carcinomas bear this "molecular fingerprint," directly demonstrating the importance of UVB-induced dipyrimidine photoproducts in nonmelanoma skin cancer (15,16). However, in the case of malignant melanoma, UVB exposure may not constitute the only critical predisposing factor. Indeed, accumulating epidemiological and molecular evidence (reviewed in ref. 17) actually supports the notion that UVA also plays a major role in the complex etiology of this particular disease. For example, the UV action spectrum for melanoma induction in fish indicates that the majority of tumors may be a...

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Pediatric liver transplantation for metabolic disorders results in excellent clinical and biochemical outcome with long survival and excellent quality of life for most recipients.

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