The mechanotransduction machinery at work at adherens junctions.

The shaping of a multicellular body, and the maintenance and repair of adult tissues require fine-tuning of cell adhesion responses and the transmission of mechanical load between the cell, its neighbors and the underlying extracellular matrix. A growing field of research is focused on how single cells sense mechanical properties of their micro-environment (extracellular matrix, other cells), and on how mechanotransduction pathways affect cell shape, migration, survival as well as differentiation. Within multicellular assemblies, the mechanical load imposed by the physical properties of the environment is transmitted to neighboring cells. Force imbalance at cell-cell contacts induces essential morphogenetic processes such as cell-cell junction remodeling, cell polarization and migration, cell extrusion and cell intercalation. However, how cells respond and adapt to the mechanical properties of neighboring cells, transmit forces, and transform mechanical signals into chemical signals remain open questions. A defining feature of compact tissues is adhesion between cells at the specialized adherens junction (AJ) involving the cadherin super-family of Ca(2+)-dependent cell-cell adhesion proteins (e.g., E-cadherin in epithelia). Cadherins bind to the cytoplasmic protein ß-catenin, which in turn binds to the filamentous (F)-actin binding adaptor protein α-catenin, which can also recruit vinculin, making the mechanical connection between cell-cell adhesion proteins and the contractile actomyosin cytoskeleton. The cadherin-catenin adhesion complex is a key component of the AJ, and contributes to cell assembly stability and dynamic cell movements. It has also emerged as the main route of propagation of forces within epithelial and non-epithelial tissues. Here, we discuss recent molecular studies that point toward force-dependent conformational changes in α-catenin that regulate protein interactions in the cadherin-catenin adhesion complex, and show that α-catenin is the core mechanosensor that allows cells to locally sense, transduce and adapt to environmental mechanical constrains.

[Gastric lipoma removed by laparoscopic subtotal gastrectomy: report of one case]. / Lipoma gástrico gigante sintomático tratado con gastrectomía subtotal laparoscópica: caso clínico.

Gastric lipoma is a rare benign gastric tumor. We report a 62-year-old man, who presented with abdominal pain, vomiting and weight loss. An upper gastrointestinal endoscopy showed a gastric antral, submucosal tumor. Abdominal ultrasound and computed tomography revealed a large antral lesion with content of high echogenicity and fat density, measuring 11 x 6 cm. The patient was treated with a laparoscopic distal subtotal gastrectomy, and a Roux-en-Y reconstruction. The patient had no postoperative morbidity, was started on a liquid diet on the third postoperative day and was discharged on the third postoperative day. The pathological study revealed a gastric lipoma with clear margins. This laparoscopic procedure represents a good alternative in the treatment of this benign gastric tumor.

Lipoma gástrico gigante sintomático tratado con gastrectomía subtotal laparoscópica: caso clínico / Gastric lipoma removed by laparoscopic subtotal gastrectomy: Report of one case

Gastric lipoma is a rare benign gastric tumor. We report a 62-year-old man, who presented with abdominal pain, vomiting and weight loss. An upper gastrointestinal endoscopy showed a gastric antral, submucosal tumor. Abdominal ultrasound and computed tomography revealed a large antral lesion with content of high echogenicity and fat density, measuring 11 x 6 cm. The patient was treated with a laparoscopic distal subtotal gastrectomy, and a Roux-en-Y reconstruction. The patient had no postoperative morbidity, was started on a liquid diet on the third postoperative day and was discharged on the third postoperative day. The pathological study revealed a gastric lipoma with clear margins. This laparoscopic procedure represents a good alternative in the treatment of this benign gastric tumor.

Resultados perioperatorios y sobrevida alejada de la pancreatoduodenectomía con resección vascular / Pancreaticoduodenectomy with vascular resection: perioperative results and long-term survival

Background: Pancreaticoduodenectomy (PDD) with vascular resection (VR) of the portal and superior mesenteric vein for locally advanced periampullary tumors is controversial. Aim: To evaluate the perioperative results and long-term survival of PDD with VR. Patients and Methods: Retrospective study. We included patients with periampullary tumors who underwent a PDD with VR between 1990 and 2008. We compared perioperative results and long-term survival with PDD without VR during the same period. We compared survival with non resected patients. Results: One hundred and eighty eight patients underwent a PDD, a VR was performed in 8 (4 percent) patients (Age: 58 +/- 14 years, Male: 4). Morbidity for PDD with and without VR was 75 percent and 59 percent (p = ns). Surgical mortality for PDD with and without VR was 0 percent and 8 percent (p = ns). In 6 of 8 patients the diagnosis was pancreatic cancer and histopathologic confirmation of vascular invasion was present in 4 patients. Long-term survival for patients with PDD with and without VR was similar (median 25 and 16 months; p = ns). Survival for patients with PDD with VR was superior to non resected patients (median 25 and 3 months; p = 0.0001). Conclusions: PDD with VR has similar perioperative results and long-term survival to PDD without VR. The survival reached with this type of surgery is far superior to non resected patients.

Introducción: La pancreatoduodenectomía (PDD) con resección vascular (RV) cuando existe invasión de la vena porta o mesentérica superior (VP-VMS) es controversial. Objetivo: Evaluar los resultados del perioperatorio y la sobrevida alejada de los pacientes sometidos a esta técnica. Material y Método: Estudio retrospectivo que incluyó a los pacientes con un tumor periampular en quienes se realizó una PDD con RV entre 1990 y 2008. Se compararon los resultados del perioperatorio y de sobrevida alejada con el grupo sometido a una PDD sin RV durante el mismo período. Se comparó también la sobrevida con los pacientes no resecados. Resultados: Se realizaron 188 PDD, en 8 (4 por ciento) de estos pacientes se realizó PDD con RV (Edad: 58 +/- 14 años, Hombres: 4). La morbilidad postoperatoria para la PDD con y sin RV fue de 75 por ciento y 59 por ciento (p = ns). La mortalidad postoperatoria para los grupos con y sin RV fue de 0 por ciento y 8 por ciento (p = ns). En 6 de los 8 pacientes el diagnóstico fue cáncer de páncreas y en 4 se confirmó histopatológicamente la invasión de VP-VMS. La sobrevida del grupo con y sin RV no tuvo diferencia significativa (medianas 25 y 16 meses; p = ns). La sobrevida de los pacientes sometidos a una PDD con RV fue superior a los pacientes no resecados (medianas 25 y 3 meses; p = 0,0001). Conclusiones: La PDD con RV obtiene resultados perioperatorios y de sobrevida alejada comparables a una PDD sin RV. La sobrevida alcanzada con esta técnica es ampliamente superior a la de los pacientes no resecados.

Hidatidosis alveolar hepática / Liver alveolar echinococcosis

La hidatidosis alveolar es infrecuente en nuestro país. La mayoría de las veces se confunde con una neoplasia hepática por su caracter infiltrante. El diagnóstico generalmente se realiza en el postoperatorio. El tratamiento muchas veces necesita de una resección hepática mayor, debido a la extensión e infiltración de la enfermedad. El presente artículo describe las características de un paciente de sexo masculino, de 57 años, que presentó un quiste hidatídico hepático fistulizado al tórax y que fue intervenido quirúrgicamente. Se le realizó una resección parcial y una marzupialización de su quiste. El estudio anatomopatológico mostró un quiste hidatídico multilocular. Actualmente se encuentra en tratamiento nutricional para completar el tratamiento quirúrgico. Además, se discuten aspectos de esta interesante e infrecuente patología.

Ultrasonografía intraoperatoria en cáncer digestivo alto / Intraoperative ultrasonography in upper gastrointestinal cancer

La ultrasonografía intraoperatoria (USIO) ha sido utilizada en diversos campos de la cirugía. En abdomen se la ha utilizado en tamizaje de la coledocolitiasis durante la colecistectomía, en la detección de tumores neuroendocrinos localizados en el páncreas, en la etapificación intraoperatoria de los tumores gastrointestinales y como apoyo en las resecciones hepáticas. En cáncer colorrectal se ha demostrado hasta un 10 por ciento de lesiones no diagnosticadas por otros métodos y, por lo tanto, en otros tumores digestivos es esperable encontrar este tipo de metástasis. El objetivo del presente trabajo es conocer los resultados obtenidos en una experiencia prospectiva con el uso de la USIO en pacientes portadores de cáncer digestivo alto, la búsqueda de metástasis hepáticas y su influencia en la correcta etapificación de estos pacientes. Se estudiaron 85 pacientes con cáncer digestivo alto en que se utilizó la USIO como método de evaluación de lesiones hepáticas diagnosticadas en el intraoperatorio o como tamizaje de metástasis. Se encontraron 26 pacientes con lesiones hepáticas (30,5 por ciento) y en 7 invasión del tumor primario al hígado (8,2 por ciento). La USIO entregó información fundamental para la toma de decisiones en el 17,5 por ciento de los casos de la presente serie. Se concluye que la USIO es una herramienta útil en la etapificación de tumores del tracto digestivo alto

Immobilized dimers of N-cadherin-Fc chimera mimic cadherin-mediated cell contact formation: contribution of both outside-in and inside-out signals.

Cell adhesion receptors of the cadherin family are involved in various developmental processes, affecting cell adhesion and migration, and also cell proliferation and differentiation. In order to dissect the molecular mechanisms of cadherin-based cell-cell adhesion and subsequent signal transduction to the cytoskeleton and/or cytoplasm leading to adapted cell responses, we developed an approach allowing us to mimic and control cadherin activation. We produced a dimeric N-cadherin-Fc chimera (Ncad-Fc) which retains structural and functional properties of cadherins, including glycosylation, Ca(2+)-dependent trypsin sensitivity and the ability to mediate Ca(2+)-dependent self-aggregation of covered microbeads. Beads covered with either Ncad-Fc or anti-N-cadherin antibodies specifically bound to N-cadherin expressing cells. Both types of beads induced the recruitment of N-cadherin, beta-catenin, alpha-catenin and p120, by lateral mobilization of preexisting cell membrane complexes. Furthermore, cadherin clustering elicited by Ncad-Fc beads triggered local accumulations of tyrosine phosphorylated proteins, a recruitment and redistribution of actin filaments, as well as local membrane remodeling. These results support a model where the adhesion of cadherin ectodomains is followed by clustering of cadherin/catenin complexes allowing signal transduction affecting both cytoskeletal reorganization and cytoplasmic signal mobilization (outside-in signaling). Interestingly, bead-cell binding was altered by agents promoting microfilament and microtubule depolymerization or tyrosine phosphorylation, indicating a possible regulation of the adhesive properties of the extracellular domain of N-cadherin by intracellular factors (inside-out signaling).

Hospitalización abreviada y colecistectomía abierta electiva: un nuevo patrón de referencia / Shortened hospitalization and elective cholecystectomy: a new referencia pattern

La colelitiasis tiene una alta prevalencia en Chile y existe una asociación importante con el cáncer de la vesícula biliar. Las tasas de colecistectomía actuales son insuficientes para satisfacer de colecistectomías. Desarrollamos un protocolo prospectivo de hospitalización abreviada y colecistectomía abierta electiva para evaluar los resultados clínicos y el grado de satisfacción del paciente, que incluyó 221 pacientes portadores de colelitiasis sintomática. Se obtuvo un promedio de estada hospitalaria postoperatoria de 1,14 días y el 92,8 por ciento de los pacientes pudieron ser dados de alta el primer día de postoperatorio. Se alcanzó un 99 por ciento de satisfacción de los pacientes frente al servicio recibido. La morbilidad fue escasa y leve. El dolor postoperatorio no fue impedimento para el alta y no afectó la evaluación realizada por los pacientes. Creemos que es posible seleccionar adecuadamente pacientes portadores de colelitiasis, para ser operados dentro de un sistema de corta hospitalización, con buenos resultados clínicos y alta satisfacción del paciente

Upregulation and redistribution of cadherins reveal specific glial and muscle cell phenotypes during wallerian degeneration and muscle denervation in the mouse.

In the present work, we investigated the expression of cadherin mRNAs in the adult neuromuscular system either under normal conditions or following experimental neurotomy. Cadherin-6, a marker of Schwann cell precursors, was not expressed in the adult peripheral nerve, while M-cadherin, cadherin-11, and N-cadherin were expressed both by glial and conjunctive cells. Moreover, the three transcripts were transiently upregulated in the distal stump of neurotomized sciatic nerve during Wallerian degeneration: N-cadherin was abundant in myelinating Schwann cells during myelin degradation, while M-cadherin and cadherin-11 may be upregulated in proliferating Schwann cells. M-cadherin, cadherin-11, and N-cadherin were also detected in myofibres and endomysium of adult gastrocnemius muscle. Following neurotomy, cadherin-11 was only transiently increased in denervated myofibres, while M-cadherin was increased and sustained for at least 21 days postoperation. In contrast, N-cadherin was not upregulated in denervated myofibres. Thus, we defined here a combination of cadherins expressed in the adult nerve and muscle, and modulated during Wallerian degeneration and muscle denervation. The comparison of the expression pattern of this combination of cadherins to the one previously described during embryonic development shows that chronically denervated Schwann and muscle cells do not reverse to embryonic state (recapitulative hypothesis), but present specific phenotypic features.

Cirugía docente en cáncer gástrico: 100 casos consecutivos / Education in gastric cancer surgery: 100 cases

Es un estudio prospectivo que incluye 100 pacientes consecutivos operados de cáncer gástrico por cirujanos en períodos de formación. Las operaciones fueron realizadas con criterio curativo o paliativo, dependiendo de la existencia o no de carcinosis peritoneal, metástasis hepáticas y/o metástasis ganglionares en tercera barrera. La docencia de la cirugía del cáncer gástrico es un desafío importante tanto para el equipo docente como para los cirujanos en formación debido a la complejidad de este tratamiento y a la importancia que éste tiene en términos de salud pública en Chile

Alta precoz y satisfacción del paciente en colecistectomía abierta electiva / Early discharge and satisfaction of patients in elective open cholecystectomy

En Chile sólo el 35 por ciento de las colecistectomías se realizan por vía laparoscópica. Dada la alta prevalencia de colelitiasis, quisimos evaluar un protocolo prospectivo de colecistectomía abierta electiva cuyo objetivo fue lograr una corta estadía hospitalaria. Se realizó con 101 pacientes de lista de espera, seleccionando aquéllos con bajo riesgo quirúrgico y pocas probabilidades de tener coledocolitiasis o cáncer vesicular asociados a colelitiasis. Se evaluaron los resultados clínicos, el dolor postoperatorio inmediato y ambulatorio, y el grado de satisfacción del paciente frente al servicio recibido. El promedio de hospitalización fue 1,12 días, el 96 por ciento de los pacientes refirió estas satisfecho de haber participado de nuestro programa y el 99 por ciento lo recomendaría a un amigo. El dolor postoperatorio fue, en la mayoría, leve y no afectó el juicio del paciente cuando fue adecuadamente tratado. No hubo mortalidad. La morbilidad fue escasa y leve. El 95 por ciento de los pacientes fue dado de alta al día siguiente de su cirugía y sólo el 3 por ciento requirió una hospitalización mayor que 2 días. Pensamos que es posible implementar programas de colecistectomía abierta electiva con tiempos de hospitalización cortos (24 h) con buenos resultados clínicos y alto grado de satisfacción del paciente

Gastrectomía paliativa en cáncer gástrico / Palliative gastrectomy in gastric cancer

El cáncer gástrico es una enfermedad de alta prevalencia en Chile y su diagnóstico se realiza frecuentemente en etapas avanzadas de la enfermedad. Se presentan los resultados obtenidos en pacientes resecados por un cáncer gástrico con metástasis hepáticas, peritoneales y/o en ganglios de tercera barrera. Se realizaron 34 operaciones en 27 meses: 24 gastrectomías totales y 10 gastrectomías parciales. Hubo dos muertes perioperatorias secundarias a neumonía en pacientes gastrectomizados totales (8,3 por ciento) y una filtración esófago-yeyunal (4,2 por ciento). La mediana de sobrevida fue 10 meses. Los pacientes con diseminación N3 exclusiva tuvieron una sobrevida actuarial a 20 meses de 38 por ciento. La gastrectomía fue un tratamiento efectivo en el alivio de los síntomas y otorgó una buena calidad de vida a los sobrevivientes

Cadherins M, 11, and 6 expression patterns suggest complementary roles in mouse neuromuscular axis development.

As the result of a systematic search for cell adhesion molecules of the cadherin family expressed in the developing mouse neuromuscular system, we obtained cDNAs coding for eight molecules of the family, including cadherins M, 11, and 6. Northern blot and in situ hybridization analysis in the mouse embryo revealed a complementary expression of these transcripts. M-cadherin is found in embryonic somitic and nonsomitic striated muscles. As far as the hypaxial musculature is concerned, M-cadherin is expressed in committed but not in migratory precursor cells. Cadherin-11 is detected in mesodermal and conjunctive tissues and transiently in the ependymal germinative layer and in the motoneuron columns of the spinal cord. Cadherin-6 is found in embryonic spinal motoneuron columns and in Schwann cell precursors. In vitro experiments confirmed the muscular, glial, and fibroblastic origins of cadherins M, 11, and 6 transcripts, respectively. Altogether, these results suggest that various cadherins are differentially involved in muscle cell, Schwann cell, and motoneuron interactions and differentiation during neuromuscular development.

Distinct location and prevalence of alpha-, beta-catenins and gamma-catenin/plakoglobin in developing and denervated skeletal muscle.

We studied the distribution of alpha-catenin, beta-catenin and gamma-catenin/plakoglobin in developing, adult and denervated mouse skeletal muscle. During primary myogenesis, all three catenins present a subsarcolemmal distribution within primary myotubes. During secondary myogenesis they accumulate at myotube-myotube contacts. In contrast to the other catenins, gamma-catenin is strongly expressed in the sarcoplasm. In adult muscle, all three catenins are localized on the presynaptic elements of the neuromuscular junction. In denervated muscles, alpha- and beta-catenins are upregulated like N- and M-cadherin, while the levels of gamma-catenin/plakoglobin remain unchanged. The developmental changes in localization and regulation of alpha- and beta-catenins in muscle compared to gamma-catenin/plakoglobin are suggestive of a privileged association of alpha- and beta-catenins with N- and M-cadherins, while gamma-catenin/plakoglobin appears to be expressed quite independently and must assume a different role during myogenesis.

Miotomía esofágica por videotoracoscopía: indicaciones, técnicas y resultados / Esophageal myotomy by videothoracoscopy: indications, techniques and results

Se presenta una serie de 12 pacientes portadores de acalasia esofágica en los que se realizó miotomía esofágica por medio de videotoracoscopia izquierda. Se describe en detalle la técnica quirúrgica y manejo perioperatorio. Se presentan complicaciones mayores en 2 pacientes y menores en otro. No hubo mortalidad. En 1 0 pacientes la deglución postoperatoria inmediata es excelente a buena. En el postoperatorio alejado se presenta disfagia recurrente en 2 pacientes que se manejan con dilataciones. La miotomía esofágica por videotoracoscopia proporciona resultados similares a otras técnicas abiertas pero con todas las ventajas de una técnica mínimamente invasiva

[Cadherins, the development and regeneration of the neuromuscular axis]. / Les cadhérines, la mise en place et la régénération de l'axe neuromusculaire.

Various cell adhesion molecules of the cadherin family characterize the neuromuscular system. During development, cadherins N and M are sequentially expressed by myogenic cells during the two waves of myoblast fusion. Two other cadherins, called 6 and 11, are also expressed during the embryonic musculature development. In adult muscle, cadherins N and M, whose expression is suppressed by muscle activity, persist only at the neuromuscular junction and are reexpressed at the surface of denervated fibers. Cadherins N, M and E are also expressed in adult peripheral nerves. Their differential localization at Schmidt-Lanterman clefts, Ranvier nodes and neuromuscular junctions suggest that these molecules contribute to the stabilization of specialized intercellular contacts. In conclusion, a combination of cadherins, the expression of which is spatially and temporally regulated, participates in the differentiation and maintenance of the organization of the various cellular and tissular components of the neuromuscular system.

Insulinoma / Insulinoma

Se presentan 3 casos de Insulinoma, vistos en nuestro Servicio durante el año 1995. Dado lo raro de esta patología se decide hacer una breve revisión del tema poniendo especial énfasis en lo que a diagnóstico bioquímico y topográfico respecta. Se discute cuál puede ser el mejor procedimiento para esto último y si realmente se justifican los esfuerzos. Se destaca el rol de la ecotomografía intraoperatoria para realizar resecciones precisas; no hubo morbimortalidad en la serie y los controles alejados han demostrado normoglicemia

Localized deposition of M-cadherin in the glomeruli of the granular layer during the postnatal development of mouse cerebellum.

M-cadherin is a Ca2+-dependent cell adhesion molecule of the cadherin family, initially localized at the areas of contact between myotubes during myogenesis, but also detected in the peripheral nerve and at the adult neuromuscular junction. In this study, searching for the expression of M-cadherin in the adult mouse brain, we observed a restricted expression of M-cadherin in one of the three layers of the cerebellar cortex: the granular layer. M-cadherin was accumulated in structures rich in synapses and other intercellular junctions where mossy fibers connect granule cell dendrites, the glomeruli. This molecule was not expressed in the cerebellum during the first steps of postnatal cerebellar neurogenesis: granule cell proliferation and migration and Purkinje cell alignment. M-cadherin expression was first detected at postnatal day (P) 11, after the establishment of the synaptic connections between mossy fibers and granule cell dendrites. It then accumulated in glomeruli during their phase of maturation which is characterized by the formation of puncta adherentia between granule cell dendrites. M-cadherin was undetectable in the cerebella of the weaver and staggerer mutants, lacking granule cells, and therefore mature glomeruli and puncta adherentia. Furthermore, other components classically associated with intercellular junctions, i.e., alpha-caterin, beta-catenin and actin filaments, closely paralleled M-cadherin appearance and colocalized with M-cadherin in the mature glomeruli. M-cadherin, which appears as a molecular marker of glomerulus maturation, might be implicated in the formation, and be the ligand, of adherens junctions encountered in this structure.

M-cadherin distribution in the mouse adult neuromuscular system suggests a role in muscle innervation.

M-cadherin belongs to the Ca(2+)-dependent cadherin family of cell adhesion molecules and was first isolated from a mouse muscle cell line cDNA library. It is specifically expressed in muscle tissue during development and is supposed to play an important role in secondary myogenesis. In the present study the expression of M-cadherin mRNA and protein and its localization were investigated in adult mouse skeletal muscle and peripheral nerve. The mRNA was abundant in embryonic legs from embryonic day (E)14 to E18. It remained expressed in new-born and adult muscles. In the adult muscle M-cadherin immunoreactivity was only detected at the neuromuscular junction, associated with perijunctional mononucleated cells and on intramuscular nerves. Peripheral nerves were also M-cadherin-positive. The molecule was found at the surface of myelinated nerve fibres where it was concentrated at the node of Ranvier. When a nerve was crushed and allowed to regenerate, M-cadherin was over-expressed at the site of nerve injury and in the distal stump. M-cadherin was also upregulated on the sarcolemma of denervated muscle fibres. Taken together, these observations point toward a much wider tissue distribution of M-cadherin than previously thought. M-cadherin might be involved not only in specific steps of myogenesis but also in some aspects of synaptogenesis, axon/Schwann cell interactions and node of Ranvier structural maintenance.