Religiosity Associated with Prolonged Survival in Liver Transplant Recipients

We tested the hypothesis that religiosity (ie, seeking God\u27s help, having faith in God, trusting in God, and trying to perceive God\u27s will in the disease) is associated with improved survival in patients with end-stage liver disease who have undergone orthotopic liver transplantation. We studied a group of 179 candidates for liver transplantation who responded to a questionnaire on religiosity during the pretransplant psychological evaluation and underwent transplantation between 2004 and 2007. The demographic data, educational level, employment status, clinical data, and results of the questionnaire were compared with the survival of patients during follow-up, regardless of the cause of any deaths. Factorial analysis of responses to the questionnaire revealed 3 main factors: searching for God (active), waiting for God (passive), and fatalism. The consistency of the matrix was very high (consistency index ? 0.92). Eighteen patients died during follow-up (median time ? 21 months). In multivariate analysis, only the searching for God factor [hazard ratio (HR) ? 2.95, 95% confidence interval (CI) ? 1.05-8.32, v2 ? 4.205, P ? 0.040] and the posttransplant length of stay in the intensive care unit (HR ? 1.05, 95% CI ? 1.01-1.08, v2 ? 8.506, P ? 0.035) were independently associated with survival, even after adjustments for the waiting for God factor, fatalism, age, sex, marital status, employment, educational level, viral etiology, Child-Pugh score, serum creatinine level, time from the questionnaire to transplantation, donor age, and intraoperative bleeding. Patients who did not present the searching for God factor were younger than those who did, but they had shorter survival times (P ? 0.037) and a 3-fold increased relative risk of dying (HR ? 3.01, 95% CI ? 1.07-8.45). In conclusion, religiosity is associated with prolonged survival in patients undergoing liver transplantation. Liver Transpl 16:1158-1163, 2010. VC 2010 AASLD

Analysis of patients' needs after liver transplantation in Tuscany: a prevalence study.

BACKGROUND: The reorganization of the healthcare system in Tuscany aims at characterizing the hospitals as a place for the treatment of acute patients. This event, together with the improvement of long-term survival after orthotopic liver transplantation (OLT), calls for a management network able to ensure effective continuity of care for patient needs in the posttransplantation period. MATERIALS AND METHODS: An observational study of prevalence has been carried out with the primary objective to evaluate patients' needs and criticalities both in routine daily life and in urgency in the posttransplantation period and the capacity of the regional health system to support them. A survey, using a semi-structured questionnaire consisting of 27 questions, was administered to all patients resident in Tuscany who underwent transplantation from 2000 to 2010. The survey tool assessed the following: socio-demographic data, personal, family and social difficulties, problems emerged in the clinical routine and urgency, resolution modality, relationships with the general practitioner and the referral specialist, and services the patients would appreciate receiving in their province of residence. RESULTS: In the study, 346 patients matched the inclusion criteria of the study, 324 gave telephone consent to participate in the survey, and 225 responded (69.4%). The most frequent difficulties were as follows: depression (39.5%), difficulty in returning to work (29.3%), low income (22.6%), lack of self-sufficiency (22.6%), addictions (19.1%) (cigarette smoking 16.4%), 12.4% eating disorders, and 18.9% other difficulties (social isolation, absence of a family network, and so on). The main reasons for dissatisfaction were as follows: difficulty to obtain the required laboratory tests and lack of a reference structure at the local health facility. Few patients have a referral specialists in their area and most of them primarily refer to the Transplant Center even late after the procedure. DISCUSSION: Early diagnosis of specific conditions (depression, addiction, and eating disorders) should be implemented in the follow-up period and services such as counselling, dietary support, rehabilitation, and social services should be provided locally. An integrated management system between the transplantation center and the local facilities (hospitals, general practitioners, primary care, and laboratories) should be implemented and referral specialized centers should be identified locally

Strategies to optimize the use of marginal donors in liver transplantation.

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD

A role for autophagy in β-cell life and death.

Autophagy is a vacuolar, self-digesting mechanism responsible for the removal of organelles and defined regions of the cytoplams. This process has, in general, a beneficial role for the cell, since it regulates the turnover of aged proteins and eliminates damaged structures. However, cells that undergo altered autophagy may be triggered to die in a non-apoptotic manner. As a matter of fact, in recent years it has become clear that dysregulated autophagy may be implicated in several disorders, such as cancer, neurodegenerative diseases and hepatic encephalopathy. We have recently shown that β-cells of type 2 diabetic subjects show signs of autophagy associated death, which may contribute to the overall loss of β-cell mass in type 2 diabetes. In addition, studies with cell lines and rodent models have demonstrated the importance of autophagy in β-cell function and survival. Altogether, the available evidence supports the view that autophagy is implicated in β-cell pathophysiology, and suggests that addressing the molecular mechanisms involved in autophagic regulation might provide clues for preventing or treating β-cell damage in diabetes

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Letter to the edito

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma (LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature

Circulating gamma-glutamyltransferase fractions in cirrhosis.

Background: Four GGT fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. Aim: To assess the behavior of fractional GGT in cirrhotic patients evaluated for liver transplantation. Methods: This was a single-center, cross-sectional study; GGT fractions were determined by gel-filtration chromatography. Results: 264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), (p<0.0001)], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), p<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; p<0.05) or total GGT (0.900, 0.869-0.925; p<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum AST, ALT, LDH, ALP and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with INR, bilirubin and LDH. Conclusions: The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of etiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range

Histopathology and ex vivo insulin secretion of pancreatic islets in gestational diabetes: A case report

Gestational diabetes (GD) results from insufficient endogenous insulin supply. No information is available on features of islet cells in human GD. Herein, we describe several properties of islets from a woman with GD. Immunohistochemical stainings and EM analyses were performed on pancreatic samples. Islet isolation was achieved by enzymatic dissociation and density gradient centrifugation. Ex vivo insulin secretion was studied in response to fuel secretagogues. Control islets were obtained from matched non-pregnant, non-diabetic women. Total insulin positive area was lower in GD, mainly due to the presence of smaller islets. β-cell apoptosis and the presence of Ki67 positive islet cells were similar in GD and controls, whereas the amount of insulin positive cells in or close to the ducts was decreased in GD. Ex vivo insulin secretion did not differ between GD and non-pregnant, non-diabetic islets. These findings suggest that in this case of human GD there might mainly be a defect of β-cell amount, not due to increased apoptosis, but possibly to insufficient regeneration

Co-localization of acinar markers and insulin in pancreatic cells of subjects with type 2 diabetes

To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic individuals (ND) and patients with type 2 diabetes (T2D). Samples from twelve ND and twelve matched T2D multiorgan donors were studied by electron microscopy, including amylase and insulin immunogold labeling; carboxypeptidase A immunofluorescence light microscopy assessment was also performed. In the pancreas from four T2D donors, cells containing both zymogen-like and insulin-like granules were observed, scattered in the exocrine compartment. Nature of granules was confirmed by immunogold labeling for amylase and insulin. Double positive cells ranged from 0.82 to 1.74 per mm2, corresponding to 0.26±0.045% of the counted exocrine cells. Intriguingly, cells of the innate immune systems (mast cells and/or macrophages) were adjacent to 33.3±13.6% of these hybrid cells. No cells showing co-localization of amylase and insulin were found in ND samples by electron microscopy. Similarly, cells containing both carboxypeptidase A and insulin were more frequently observed in the diabetic pancreata. These results demonstrate more abundant presence of cells containing both acinar markers and insulin in the pancreas of T2D subjects, which suggests possible conversion from one cellular type to the other and specific association with the diseased condition