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...

The hepatopulmonary syndrome is an increasingly important vascular complication of cirrhosis where microvascular dilatation impairs arterial oxygenation in the setting of liver disease. This syndrome is identified in as many as 20% of patients evaluated for liver transplantation and results in increased mortality. No clearly effective medical therapies are available, and liver transplantation is the only established treatment. Pathophysiologic insights obtained from experimental models may lead to the development of novel and effective medical treatments.

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We report the design, synthesis, characterization and in vitro testing of a novel nanodrug based on a covalent linking model that allows intracellular controlled release of the pharmaceutical payload. A new synthetic strategy is implemented by direct coupling of as-synthesized (pyridin-2-yldisulfanyl)alkyl carbonate derivatives of camptothecin (CPT) with thiol groups of silica hybrid nanoparticles containing a non-porous core and a mesoporous shell. Upon reaction with thiols in physiological conditions, disulfide bridge cleavage occurs, releasing the naked drug after an intramolecular cyclization mechanism.Additional incorporation of a fluorophore into particles core facilitates imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa cervix cancer cells confirms that nanoparticles enter the cells by endocytosis but are able to escape from endo-lysosomes and enter the cytosolic compartment to release their cargo. The incorporation to cells of L-buthioninesulfoximine, a glutathione inhibitor allows concluding that the intracellular releasing mechanism is mainly driven by the reducing activity of this tripeptide. This camptothecin nanoplatform shows the same cytotoxic activity than the free drug and is clearly superior to those release systems depending on enzymatic hydrolysis (as determined by calculation of the IC 50 ratios).

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