Prognostic models to predict survival in patients with pancreatic cancer: a systematic review

BackgroundPancreatic ductal adenocarcinoma (PDAC) has poor survival. Current treatments offer little likelihood of cure or long-term survival. This systematic review evaluates prognostic models predicting overall survival in patients diagnosed with PDAC.MethodsWe conducted a comprehensive search of eight electronic databases from their date of inception through to December 2019. Studies that published models predicting survival in patients with PDAC were identified.Results3297 studies were identified; 187 full-text articles were retrieved and 54 studies of 49 unique prognostic models were included. Of these, 28 (57.1%) were conducted in patients with advanced disease, 17 (34.7%) with resectable disease, and four (8.2%) in all patients. 34 (69.4%) models were validated, and 35 (71.4%) reported model discrimination, with only five models reporting values >0.70 in both derivation and validation cohorts. Many (n = 27) had a moderate to high risk of bias and most (n = 33) were developed using retrospective data. No variables were unanimously found to be predictive of survival when included in more than one study.ConclusionMost prognostic models were developed using retrospective data and performed poorly. Future research should validate instruments performing well locally in international cohorts and investigate other potential predictors of survival.     

Diagnosis of intrahepatic cholangiocarcinoma by Raman spectroscopy provides high efficiency: A protocol for systematic review and meta-analysis

Background:We aim to evaluate the efficiency of Raman spectroscopy (RS) in diagnosing suspected patients with intrahepatic cholangiocarcinoma (ICC), manifested by diagnostic sensitivity, specificity, and accuracy.Methods:We will research widely the articles concerning the use of RS in ICC through authenticated database including PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, Cochrane Library, and CNKI between January 2012 and November 2020, retrieving at least 1500 spectra with strict criteria. This study will be carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We are going to summarize the test performance using random effects models.Results:Based on the pooled sensitivity, specificity, and diagnostic accuracy, we intend to provide the relative diagnostic efficiency in ICC through RS.Conclusion:Through this systematic review and meta-analysis, we intend to provide the pooled sensitivity, specificity and diagnostic accuracy of RS in the diagnosis of suspected ICC. Other parameters like positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver operating characteristics (SROC) curve will also be calculated and related figures will be drawn to help illustrate the efficacy of RS in the diagnosis of ICC.     

Epidermal growth factor receptor inhibition by erlotinib prevents vascular smooth muscle cell and monocyte–macrophage function in vitro

IntroductionVascular smooth muscle cells (VSMCs) and monocyte–macrophages play a central role during the development of chronic allograft injury, which still remains an important challenge in organ transplantation. Inflammation, fibrosis and accelerated arteriosclerosis are typical features for chronic allograft injury. Growth factors participate in cell proliferation, differentiation and migration in this pathological process.ObjectiveHere we studied the role of epidermal growth factor receptor (EGFR) in VSMC and monocyte–macrophage function in vitro. EGFR inhibition by erlotinib, a selective EGF tyrosine kinase inhibitor, was studied in VSMC proliferation and migration as well as monocyte–macrophage proliferation and differentiation.Materials and methodsRat coronary artery SMCs were used for VSMC studies. As a model for monocyte–macrophage proliferation and differentiation human monocytic cell line U937 was used. Phorbol ester TPA was used to induce these cells to differentiate into macrophages.ResultsPlatelet-derived growth factor (PDGF)-B, a known VSMC inducer, caused 2.1-fold stimulation in VSMC proliferation compared to non-stimulated VSMC. Erlotinib prevented this VSMC proliferation in a dose-dependent manner, p < 0.001 in all groups compared to controls. PDGF-B stimulation increased VSMC migration to 2.5-fold when compared with non-stimulated cells. Erlotinib decreased VSMC migration dose-dependently and this effect was significant with all doses, p < 0.05. Erlotinib inhibited dose-dependently the proliferation of U937 monocytic cells, p < 0.001. Erlotinib prevented also TPA-induced macrophage differentiation in a dose-dependent way, p < 0.05.DiscussionErlotinib significantly prevents VSMC proliferation and migration in vitro. Erlotinib inhibited also significantly both monocyte proliferation and differentiation. Our data suggest that EGFR inhibition in VSMC and monocyte function has beneficial effects on chronic allograft injury.     

Liver Transplantation After Hematopoietic Stem Cell Transplant for the Treatment of Sickle Cell Disease: A Case Report

Sickle cell anemia is the most common of the hemoglobinopathies, in which the abnormal hemoglobin formed in deoxygenation states undergoes a polymerization process with consequent erythrocyte deformation and vaso-occlusive events. The need for multiple blood transfusions, prolonged ineffective erythropoiesis, hemolysis, and increased iron absorption can cause iron overload in the liver, leading to liver fibrosis. Hematopoietic stem cell transplantation (HSCT) is currently the only treatment with a curative potential for this disease and can establish normal complete or partial donor-derived erythropoiesis and stabilize or restore function in affected organs, preventing further deterioration of function. However, it does not reverse preexisting liver fibrosis and siderosis. One of the possible complications of patients who undergo HSCT is chronic liver disease, which has a multifactorial cause, with iron overload being an important factor. In the long term, the prevalence of chronic liver disease in HSCT patients, including cirrhosis and its complications, can be significant. Solid organ transplantation after allogeneic hematopoietic cell transplantation for end-organ failure remains a very rare event. It may offer a valuable treatment strategy in selected recipients, although it is associated with significant morbidity and mortality. We report the case of a patient with sickle cell anemia who underwent HSCT and developed severe liver dysfunction requiring liver transplantation 13 years after the procedure. We found no previous report in the literature of orthotopic liver transplant after HCT for the treatment of sickle cell disease.     

Importance of Preventing Inadvertent Perioperative Hypothermia During Liver Transplant

BackgroundInadvertent perioperative hypothermia (IPH) leads to a series of deleterious effects that can be especially in complex procedures such as liver transplant. The implementation of a protocol is key to ensure the patient's normothermia.MethodsA cohort of 209 patients who underwent liver transplant in a tertiary hospital in a period between January 2016 and December 2018 was retrospectively analyzed. The patients were divided into 2 groups: group 1, patients with normothermia (core body temperature ≥ 36°C) and group 2, patients with hypothermia (core body temperature < 36°C). Mortality between both groups at 1 month, 1 year, and 3 years is compared. Postoperative morbidity is also compared.ResultsThe incidence of IPH is 21.5%. Patients with normothermia present with statistical significance: a lower mortality at 1 year; a lower need for transfusion of platelets, plasma, fibrinogen consumption, or massive polytransfusion; and lower primary graft dysfunction, graft and surgical complications, rejection, hemodynamic complications, and metabolic and surgical reintervention.No significant differences were found in mortality at 1 month or 3 years in the need for prolonged mechanical ventilation; hospital readmission; length of stay in the intensive care unit or in hospital stay; rate of red blood cell transfusion; vascular, biliary, respiratory, or digestive complications; refractory ascites; or neurologic, kidney, hematological, endocrine, thrombotic, nutritional, or infectious issues.ConclusionsThe incidence of IPH is relatively low in our patients, based on what is described in the literature, and in most cases it is mild. There is a reduction in complications fundamentally related to the consumption of blood products and the graft.     

Italian Clinical Practice Guidelines on Cholangiocarcinoma – Part II: Treatment

Currently, the only curative treatment for cholangiocarcinoma (CCA) is surgical resection, though this treatment is possible in less than 40% of patients. However, recent improvements in preoperative management have led to a higher number of patients who are candidates for this procedure. For unresectable patients, progress is ongoing in terms of locoregional and chemoradiation treatments and target therapies, especially in the definition of patient selection criteria. This is the second part of the Italian CCA guidelines, dealing with CCA treatment, that have been formulated in accordance with Italian National Institute of Health indications and developed according to the GRADE method and related advancements.     

Risk Factors Associated With New-Onset Diabetes After Liver Transplant: A Case Control Study

BackgroundNew-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant.MethodThis was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables).ResultsMultiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12–6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02–7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P < .001).ConclusionPre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant.