Training in animal models could help endoscopists overcome the learning curve before starting ESD in humans.

No abstract

Introduction: the elevated risk of complications and technical complexity of endoscopic submucosal dissection (ESD) has limited its implementation in our medical system.Objective: to design and evaluate a training program for learning the ESD technique.Methods: four endoscopists with no experience with ESD underwent a 4-step training program: 1) review of the existing literature, didactic material, and theoretical aspects of ESD; 2) ESD training in an ex-vivo animal model; 3) ESD training in an in-vivo animal model (supervised by ESD expert); and 4) ESD performance in a patient. A standard gastroscope and an ESD knife (IT, Flex or Hook-knife Olympus ® ) were employed. The classical ESD technique was performed: rising of the lesion, circumferential incision, and submucosal dissection.Results: ex-vivo animal model: 6 x swine stomach/esophagus -cost < 100 euro; 6 x ESD: antrum (n = 2), body (n = 3) and fundus/cardia (n = 1)-; size of resected specimen: 4-10 cm; ESD duration: 105-240 minutes; therapeutic success: 100%; complications: perforation (1/6: 16%) sealed with clips. In-vivo animal model: 6 ESD (antrum/body of stomach: 4; esophagus: 2); size: 2-5 cm; duration: 40-165 minutes; success: 100%; complications: 0%. Patient: ESD of a gastric lesion located in the antrum/body; size: 3 cm; duration 210 minutes; a complete resection was achieved; no complications.Conclusions: the results of the present study support the usefulness of this model for learning ESD in our system. Key words: Endoscopic submucosal dissection. ESD. Submucosal resection. Large endoscopic resection. INTRODUCTIONEndoscopic mucosal resection (EMR) consists of resecting a superficial tumor of the gastrointestinal tract (esophagus, stomach, colon or rectum) by endoscopic means with curative intention (R0 resection) (1-5). An EMR-resected lesion may be submitted for pathological examination. One of the advantages of EMR compared with surgical resection is its lower morbidity/mortality and cost. At present EMR has become widely available in clinical practice in both Asian and Western countries (1-5). However, EMR presents a number of limitations: a) technical difficulty; b) risk for complications: bleeding (2-29%), perforation (0.36%) and stenosis (mainly in the esophagus); and c) restricted to superficial lesions with no lymphatic spread and size < 1-1.5 cm (1-8). Lesions with a diameter > 1.5 cm cannot be completely resected with a single EMR procedure, and repeated mucosectomies (several fragments) or endoscopic submucosal dissection (ESD) (allowing to resect the entire lesion in a single piece) will be required (2). It is generally assumed that it is better to resect tumoral lesions in single pieces, as we can be sure the tumor has been completely resected, and it also facilitates sample orientation at the time of the pathology study (8)(9)(10)(11)(12)(13)(14)(15). Furthermore, ESD allows to perfom wider and deeper resections versus EMR (2). However, the learning curve for ESD (high technical difficulty) is longer (compared with EMR), and compli...

Chromogranins (Cgs) constitute the main protein component in the vesicular matrix of large dense core vesicles (LDCV). These acidic proteins have been implicated in several physiological processes such as vesicle sorting, the generation of bioactive peptides and the accumulation of soluble species inside LDCV. This latter feature of Cgs accounts for the ability of vesicles to concentrate catecholamines and Ca 2+. Indeed, the low affinity and high capacity of Cgs to bind solutes at the low pH of the LDCV lumen seems to be behind the delay in the neurotransmitter exit towards the extracellular milieu after vesicle fusion. The availability of new mouse strains lacking Cgs in combination with the arrival of several techniques for the direct monitoring of exocytosis (like amperometry, patchamperometry and intracellular electrochemistry), have helped advance our understanding of how these granins concentrate catecholamines and Ca 2+ in LDCV, and how they influence the kinetics of exocytosis. In this review, we will discuss the roles of Cgs A and B in maintaining the intravesicular environment of secretory vesicles and in exocytosis, bringing together the most recent findings from adrenal chromaffin cells.

The mineralocorticoid receptor (MR), a member of the nuclear receptor family, mediates the action of aldosterone in target epithelia, enhancing sodium reabsorption. In addition, MR may have other physiological functions in nonepithelial tissues. Altered expression or inappropriate activation of cardiac MR is directly linked to the development of cardiac fibrosis, and MR blockade is beneficial for the treatment of heart failure. However, the physiological role, activation status, and target genes of MR in the heart are poorly known. Because ligand-free steroid receptors are typically cytoplasmic and translocate to the nucleus upon ligand binding, we examined the subcellular localization of MR under different corticosteroid levels using subcellular fractionation and immunostaining. Our results demonstrate that MR is a chromatin-bound factor in mouse left ventricle and in a cultured model of cardiomyocytes, HL-1 cells, regardless of circulating corticosteroid levels. Immunohistochemical localization of MR in human heart confirms the subcellular localization pattern. Mutation of nuclear localization signals (NLSs) demonstrates that MR constitutive nuclear localization mainly depends on the synergistic contribution of NLS0 and NLS1. Constitutive nuclear localization in HL-1 cells can be reverted by cotransfection of heat shock protein 90. Heat shock protein 90 expression levels in the mouse heart and HL-1 cells are lower than those found in other tissues, suggesting that low levels of cochaperones render MR NLSs hyperactive in cardiomyocytes. Even though MR is constitutively nuclear, corticosteroids still control the transactivation properties of the receptor in a model promoter, although other MR ligand-independent activities cannot be excluded.