Recent Developments in Surgery Minimally Invasive Approaches for Patients Requiring Pancreaticoduodenectomy

Over the past decade, minimally invasive surgery has been introduced as a means to allow manipulation of delicate tissues with outstanding visualization of the surgical field. The purpose of this article is to review the available literature regarding early postoperative outcomes and the technical challenges of minimally invasive pancreaticoduodenectomy, including robotic techniques. Herein, we provide a retrospective review of all published studies in the English literature in which a minimally invasive pancreaticoduodenectomy was performed. The reported advantages of minimally invasive pancreaticoduodenectomy include better visualization, faster recovery time, and decreased length of hospital stay. In cases of robotic approaches, some of the proposed advantages include increased dexterity and a superior ergonomic position for the operating surgeon. To our knowledge, few studies have reported results comparable to open techniques in oncologic outcomes with regard to the number of lymph nodes resected and clear margins obtained. An increasing number of pancreatic resections are being performed using minimally invasive approaches. It remains to be determined if the benefits of this technique outweigh its longer operative times and higher costs

Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms.

BACKGROUND: The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats. METHODS: Diabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and ß-adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3ß as well ß-1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR. RESULTS: OB preserved papillary muscle contractility (85 vs 27% of ND), ß-adrenergic response (103 vs 65% of ND), as well ß1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3ß phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium. CONCLUSIONS: OB displays a significant beneficial effect against the alterations of contractility and ß-adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of ß1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3ß

Efecto sobre la regeneración de la capa íntima vascular de la heparina cálcica y la enoxaparina

An experimental study was carried out in dogs in arder tocompare the effect of calcium heparine and enoxaparineover the development of intima/ hyperplasia. A model ofintima! hyperplasia developed by the Basic Departmentof Surgery was employed. When comparing the differentseries to the control group no significan/ differences inthe development of intima! hyperplasia could be found;therefore no inhibiting effect over /he development ofintima! hyperplasia could be demonstrated far any of thedrugsSe realizó un trabajo experimental en perros a efectos decomparar los efectos de la heparina cálcica y laenoxaparina sobre el desarrollo de hiperplasia intima!.Se utilizó un modelo de hiperplasia intima! desarrolladoen el Depto. Básico de Cirugía.No se encontraron diferencias significativas en eldesarrollo del fenómeno analizado en las distintas seriesestudiadas con respecto al grupo control, por lo cual nose pudo poner en evidencia un efecto inhibidor sobre eldesarrollo de hiperplasia intima! para ninguno de losfármacos estudiados

Modelo experimental para el desarrollo de hiperplasia intima/

Based on the necessity of practica! experimental modelsfar the obtaining of /esions of intima/ hyperplasia, theauthors present their experience at the Departamento deCirugía Básica (Basic Surgery Dept.) of a model ofarterial /esion in dogs by means of arterial dilatation withFoley sound. This was performed in 20 animals whichwere divided into series according to evolutions of 7, 1 O,and 15 days. Arteries were studied macro andmicroscopically; lesions of intima/ hyperplasia wereobtained in the 15 day evolution series.Ante la necesidad de obtener modelos experimentalesprácticos para la obtención de lesiones de hiperplasiaintima!, los autores comunican la experiencia delDepartamento Básico de Cirugía en el desarrollo de unmodelo de lesión arterial en perros, por medio de ladilatación arterial con sonda Foley.Se intervinieron 20 animales, dividiéndolos en seriessegún la evolución de 7, 1 O y 15 días.Las arterias fueron estudiadas del punto de vista macroy microscópico, obteniéndose lesiones de hiperplasiaintima/ en la serie con evolución de 15 días

Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8+ T cells

The autoimmune pathogenesis of type 1 diabetes (T1D) involves cellular infiltration from innate and adaptive immune subsets into the islets of Langerhans within the pancreas; however, the direct cytotoxic killing of insulin-producing β-cells is thought to be mediated primarily by antigen-specific CD8+ T cells. Despite this direct pathogenic role, key aspects of their receptor specificity and function remain uncharacterized, in part, due to their low precursor frequency in peripheral blood. The concept of engineering human T cell specificity, using T cell receptor (TCR) and chimeric antigen receptor (CAR)-based approaches, has been demonstrated to improve adoptive cell therapies for cancer, but has yet to be extensively employed for modeling and treating autoimmunity. To address this limitation, we sought to combine targeted genome editing of the endogenous TCRα chain gene (TRAC) via CRISPR/Cas9 in combination with lentiviral vector (LV)-mediated TCR gene transfer into primary human CD8+ T cells. We observed that knockout (KO) of endogenous TRAC enhanced de novo TCR pairing, which permitted increased peptide:MHC-dextramer staining. Moreover, TRAC KO and TCR gene transfer increased markers of activation and effector function following activation, including granzyme B and interferon-γ production. Importantly, we observed increased cytotoxicity toward an HLA-A*0201+ human β-cell line by HLA-A*02:01 restricted CD8+ T cells engineered to recognize islet-specific glucose-6-phosphatase catalytic subunit (IGRP). These data support the notion of altering the specificity of primary human T cells for mechanistic analyses of autoreactive antigen-specific CD8+ T cells and are expected to facilitate downstream cellular therapeutics to achieve tolerance induction through the generation of antigen-specific regulatory T cells

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

Peer reviewedPublisher PD

CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo

Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2