OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

Cardiovascular (CV) diseases are recognized longterm causes of death after liver transplantation (LT). The objective of this multicenter study was to analyze the prevalence and the evolution of CV risk factors and CV morbidity and mortality in 1819 LT recipients along 5 years after LT. The influence of baseline variables on survival, morbidity, and mortality was studied. There was a continuous and significant increase of the prevalence of all the CV risk factors (except smoking) after LT. CV diseases were the fourth cause of mortality in the 5 years after LT, causing 12% of deaths during the follow-up. Most CV events (39%) occurred in the first year after LT. Preexisting CV risk factors such as age, pre-LT CV events, diabetes, metabolic syndrome, and hyperuricemia, and mycophenolate-free immunosuppressive therapy, increased post-LT CV morbidity and mortality. The development of new-onset CV risk factors after LT, such as dyslipidemia and obesity, independently affected late CV morbidity and mortality. Tacrolimus and steroids increased the risk of posttransplant diabetes, whereas cyclosporine increased the risk of arterial hypertension, dyslipidemia, and metabolic syndrome. In conclusion, CV complications and CV mortality are frequent in LT recipients. Preexisting CV risk factors, immunosuppressive drugs, but also the early new onset of obesity and dyslipidemia after LT play an important role on late CV complications. A strict metabolic control in the immediate post-LT period is advisable for improving CV risk of LT recipients. Liver Transplantation 23 498-509 2017 AASLD.

The aim of this study was to analyze the donor risk factors associated with second orthotopic liver transplantation (reOLT) and graft loss after OLT within 1 month. A total of 649 OLTs performed in 11 centers in Spain during the period from 1992 to 1993 were analyzed retrospectively. Eleven donor and recipient variables were studied. Biochemical evolution of the OLT, biliary and arterial complications, patient status (alive, retransplanted, or dead), and follow-up were also recorded. Bivariate study demonstrated that extended preservation ( > 12 hr) was associated with increased biliary complications (P = 0.02), and lower prothrombin time (P = 0.04). In a logistic model regression for biliary complications, ischemia > 12 hr was an independent risk factor (odds ratio = 2.2, 95% confidence interval [CI] = 1.1-4.3). The multivariate Cox proportional model of potential risk factors showed that only urgent reOLT (relative risk [RR] = 2.7, 95% CI = 1.4-5.4) was independently associated with higher 30-day mortality. Donor plasma sodium > 155 mmol/L (RR = 1.4, 95% CI = 1.0-2.2) and incompatible ABO graft (RR = 3.2, 95% CI = 1.3-7.9) were independently associated with increased rate of reOLT before 30 days. Donor plasma sodium > 155 mmol/L (RR = 2, 95% CI = 1.1-3.6) and incompatible graft (RR = 3.3, 95% CI = 1.4-8.2) were independently associated with graft loss (death or reOLT) before 1 month. We conclude that cold ischemia should be kept less than 12 hr in order to avoid biliary complications. Donors over 60 years old or with plasma sodium > 155 should be carefully evaluated before OLT.

The higher mortality rate in men than in women after hip fracture may in part be explained by the poor nutritional status in men.

GalN) is a suitable experimental model of hepatocellular injury. The induction of oxidative and nitrosative stress participates during D-GalN-induced cell death in cultured rat hepatocytes. This study aimed to identify protein expression changes during the induction of apoptosis and necrosis by D-GalN in cultured human hepatocytes. Methods: A proteomic approach was used to identify the proteins involved and those altered by tyrosine nitration. A high dose of D-GalN (40 mM) was used to induce apoptosis and necrosis in primary culture of human hepatocytes. Cellular lysates prepared at different times after addition of D-GalN were separated by two-dimensional electrophoresis. Gel spots with an altered expression and those matching nitrotyrosine-immunopositive proteins were excised and analyzed by mass spectrometry. Results: D-GalN treatment upregulated microsomal cytochrome b5, fatty acid binding protein and manganese superoxide dismutase, and enhanced annexin degradation. D-GalN increased tyrosine nitration of four cytosolic (Hsc70, Hsp70, annexin A4 and carbonyl reductase) and three mitochondrial (glycine amidinotransferase, ATP synthase b chain, and thiosulfate sulfurtransferase) proteins in human hepatocytes. Conclusions: The results provide evidences that oxidative stress and nitric oxide-derived reactive oxygen intermediates induce specific alterations in protein expression that may be critical for the induction of apoptosis and necrosis by D-GalN in cultured human hepatocytes. Hepatic injury induced by D-galactosamine (D-GalN) is a suitable experimental model of hepatocellular injury. D-GalN is metabolized to UDP-hexosamines and UDP-N-acetylhexosamines in hepatocytes. This effect depletes the intracellular pool of UTP (1) causing a transient arrest in the cellular transcription and protein synthesis that alters hepatocellular function. However, the exact molecular mechanisms responsible for D-GalNinduced apoptosis and/or necrosis in hepatocytes are not well understood. Diverse intracellular regulatory signals affect the induction of apoptosis and necrosis (2). Nowadays, there is growing evidence that changes in intracellular redox state appear to regulate critical biological responses. Reactive oxygen species influence signal transduction and transcription factors, and play a central role in the pathophysiology of liver injury (3). In this sense, we (4) and others (5) have shown that oxidative stress shifts cell death from apoptotic to necrotic pathways in D-GalN-treated rat hepatocytes. Mitochondria, as the most important cellular sources of free radicals, play an essential role in the development of cell death by apoptosis or necrosis.We have previously shown that nitric oxide (NO) mediates apoptosis by D-GalN in primary culture of rat hepatocytes (6, 7). NO has been recognized as a critical mediator in normal hepatocyte

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The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.