We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and premalignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogenactivated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.

We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells.

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Biliary complications are being increasingly encountered in post liver transplant patients because of increased volume of transplants and longer survival of these recipients. Overall management of these complications may be challenging, but with advances in endoscopic techniques, majority of such patients are being dealt with by endoscopists rather than the surgeons. Our review article discusses the recent advances in endoscopic tools and techniques that have proved endoscopic retrograde cholangiography with various interventions, like sphincterotomy, bile duct dilatation, and stent placement, to be the mainstay for management of most of these complications. We also discuss the management dilemmas in patients with surgically altered anatomy, where accessing the bile duct is challenging, and the recent strides towards making this prospect a reality. Core tip: Biliary complications are being increasingly encountered in post liver transplant patients because of increased volume of transplants and longer survival of these recipients. Overall management of these complications may be challenging, but with advances in endoscopic techniques, majority of such patients are being dealt with by endoscopists rather than the surgeons. Our review article discusses the recent advances in endoscopic tools and techniques which have proved ERCP with various interventions, like sphincterotomy, bile duct dilatation, and stent placement, to be the mainstay for management of most of these complications. We also deliberate the management dilemmas in patients with surgically altered anatomy, where accessing the bile duct is challenging, and the recent strides towards making this prospect a reality.

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