YAP/TAZ regulates the expression of proteoglycan 4 and tenascin C in superficial-zone chondrocytes.

The roles of cell division control protein 42 homologue (CDC42) and actin polymerisation in regulating the phenotype of superficial-zone chondrocytes (SZCs) have been demonstrated in vitro; however, the signalling pathway(s) downstream have yet to be fully elucidated. The study hypothesis was that Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) act downstream to regulate proteoglycan 4 (PRG4) and tenascin C (TNC). Bovine SZCs grown in monolayer were treated with ML141 (CDC42 inhibitor) or the actin depolymerising agents, latrunculin B and cytochalasin D, to determine the effect on YAP/TAZ. Verteporfin (YAP/TAZ inhibitor) and YAP/TAZ siRNA-mediated knockdown were used to determine their role in regulating PRG4 and TNC. ML141 treatment reduced total YAP/TAZ protein, nuclear TAZ levels and the YAP/TAZ target gene, connective tissue growth factor (CTGF) mRNA levels. Latrunculin B decreased nuclear TAZ, while cytochalasin D treatment trended towards increased nuclear TAZ (p = 0.06), correlating with decreased and increased CTGF mRNA levels, respectively. Verteporfin treatment decreased PRG4 and TNC expression, with no effect on actin polymerisation. siRNA-mediated knockdown of YAP/TAZ revealed that PRG4 was regulated by YAP/TAZ while TNC was regulated by TAZ only. As cytochalasin D can activate myocardin-related transcription factor-A (MRTF-A), siRNA-mediated knockdown was performed to determine the role of MRTF-A in regulating YAP/TAZ. Although nuclear TAZ decreased, no significant changes in total protein levels were observed. Findings suggested that CDC42 and actin polymerisation regulated SZCs through multiple actin-regulated pathways. Understanding the regulation of these chondroprotective molecules may have important implications for prevention/treatment of osteoarthritis.

Tumor buding y el cáncer colorrectal / Budding tumour and colorectal cancer

Introduction: Tumour budding (TB) is defined as the presence of clusters of tumoural cells detaching from invasive margin of main tumor. It is an independent adverse prognostic factor in colorectal cancer. The aim of this study is to determinate if severity of tumor budding is associated with others prognostic factors in colorectal cancer. Materials and Methods: The study group is composed by 43 patients (27 males and 16 females; average age 73.4 years, (27-91) with colorectal cancer who underwent curative surgery. The histologic method of tumour budding used in this study was described by Nakamura. The applied statistical software was G-Stat 2.0. Statistical significance is accepted at p < 0.05. Results: High grade of TB was significantly associated with lymph node metastasis (p = 0.027), infiltrative tumour-border configuration (p = 0.016), lymphvessels invasion (p = 0.02), perineural invasion (p = 0.009) and tumor deposits (p = 0.018). There was a significant association with low grade of TB and peritumoural lymphocytic infiltration (p = 0.004). Conclusions: High grade of TB is significantly associated with other adverse prognostic factors as lymph node metastasis, infiltrative tumour-border configuration, lymphvessels invasion, venous invasion, perineural invasion and tumor deposits; and low grade of TB with favorable prognostic factor as peritumoural lymphocytic infiltration in colorectal cancer. Tumour budding can help to identify hig-risk patients with colorectal cancer.

Introducción: El tumor budding (TB) es la presencia de células tumorales aisladas o en pequeños grupos situadas en el frente infiltrante del tumor. Su hallazgo en alto grado es un factor de mal pronóstico independiente del cáncer colorrectal. El objetivo de este trabajo es determinar si el grado de TB está asociado con otros factores pronósticos del cáncer colorrectal. Materiales y Métodos: Se analizaron retrospectivamente 43 pacientes (27 varones y 16 mujeres) con una edad media de 73,4 años (27-91) intervenidos por cáncer colorrectal. El método histológico utilizado para determinar la presencia de TB fue el descrito por Nakamura en 2005. El análisis estadístico se realizó con el programa G-Stat2.0. Las diferencias se consideraron significativas si p < 0,05. Resultados: La presencia de TB de alto grado se asocia significativamente con la presencia de metástasis a ganglios linfáticos (p = 0,027), patrón de crecimiento infiltrativo (p = 0,016), invasión linfática (p = 0,02), perineural (p = 0,009) y depósitos tumorales discontinuos (p = 0,018). El TB de bajo grado se relaciona con la presencia de reacción linfocitaria peritumoral (p = 0,004). Conclusiones: El tumor budding alto grado se asocia con otros factores de mal pronóstico, como metástasis a ganglios linfáticos, crecimiento infiltrativo, invasión linfática, perineural y depósitos tu-morales discontinuos; y el tumor budding bajo grado con factores de buen pronóstico del cáncer colorrectal como reacción linfocitaria peritumoral. El análisis del grado de tumor budding podría ayudar a identificar a pacientes de peor pronóstico con cáncer colorrectal.

Is radical surgery feasible in liver hydatid cysts in contact with the inferior vena cava?

BACKGROUND: Cysts in contact with the inferior vena cava (IVC) represent a challenge for hepato-pancreatico-biliary surgeons. Although the literature on the topic is scarce, the most widely accepted approach is conservative surgery. Partial cyst resection is recommended, because radical resection is considered a high-risk procedure. STUDY DESIGN: This was a retrospective study over the period January 2007-December 2012. We operated on 103 patients with liver hydatidosis. A total of 32 patients (31 %) had a liver cyst in contact with the IVC. We proposed a cyst classification based on location of the cyst and length of contact and degrees of involvement of the IVC. RESULTS: Median size of the contacting cyst measured by computed tomography (CT) was 12 cm. On CT, median length of contact with the IVC was 37 mm. The median degree of involvement was 90°. Radical surgery was performed in 20 patients (62.5 %). No IVC resection was done. Morbidity rate was 28 %, and mortality was 3 %. In follow-up (median 27 months), no relapses or problems related to IVC flow were detected. Postoperative stay and transfusion rate were higher in the conservative surgery group, but these patients presented fewer complications. There was no relationship between circumferential grades and length of contact with the IVC and the type of surgery performed. CONCLUSIONS: Liver hydatid cysts in contact with the IVC are large cysts usually located in the right liver. They do not normally cause clinical symptoms related to IVC contact. Radical surgery is feasible, and was performed in 60 % of our series, but it is technically demanding. We propose a classification of cysts in contact with the IVC.

Walled-off pancreatic necrosis.

Acute severe pancreatitits may be complicated by the development of 'walled-off pancreatic necrosis' (WOPN), which is characterised by a mixture of solid components and fluids on imaging studies as a consequence of organised pancreatic tissue necrosis. We present here an overview of the definition, clinical features, and diagnostic and therapeutic management of this clinical condition, which is mostly based on consensus as adequate clinical trials are lacking.

Cysto-biliary communication in liver hydatidosis.

BACKGROUND: Liver hydatidosis is a severe health problem in endemic areas. Due to migration from these countries to other zones, now it is a worldwide problem. Liver hydatidosis can provoke many complications (abscess, fistula to adjacent organs, migration, etc.), but the most frequent and one of the most severe complication is the communication between the cyst and the biliary tree. AIM: The aim of this study is to perform a review on the epidemiology, clinical features, diagnostic methods, and therapeutic options to treat the communication between the cyst and the biliary tree. RESULTS: Due to the lack of randomized clinical trial or meta-analysis on this topic, we performed a classical review and included our personal algorithm. CONCLUSIONS: The communication between the cyst and the biliary tree varies from a small communication to a frank intrabiliary rupture. The percentage of patients with the communication between the cyst and the biliary tree is not well known because there is no accepted definition. The therapeutic options are multiple and related to the size of the communication, the location of the cyst, and the experience of the hepatobiliary surgeon. ERCP is now an important tool for the treatment of the communication between the cyst and the biliary tree.

Three trocars laparoscopic resection of angiomyolipoma of the liver.

Angiomyolipoma of the liver (AML) is an infrequent neoplasm composed of three tissues (adipose, muscle and vessels). In spite of advances in radiology, preoperative correct diagnosis is difficult. Clasically, a conservative management strategy was adopted in patients with asymptomatic tumors less than 5 cm with undoubtful diagnosis. But after publishing some few cases of malignant angiomyolipoma a more radical has been advocated. Laparoscopic resection of liver tumors is becoming a excellent approach for operating on benign liver tumors. Usually is performed using five trocars but in some cases a less invasive technique with three trocars could be used. We present a laparoscopic resection of liver angiomyolipoma in a 65 year-old male using only three trocars and also discuss the optimal management of AML and technical tips of three-trocar technique.

The use of isotonic fluid as maintenance therapy prevents iatrogenic hyponatremia in pediatrics: a randomized, controlled open study.

OBJECTIVES: Hypotonic fluids are widely used in pediatrics. Several articles have reported the risk of iatrogenic hyponatremia secondary to this practice. We primarily intend to determine whether the use of isotonic fluids prevents hyponatremia and, secondly, whether these fluids increase the incidence of adverse events. STUDY DESIGN: One hundred twenty-two pediatric patients hospitalized in intensive care unit requiring maintenance fluid therapy were randomized to receive isotonic fluids (isotonic group, NaCl = 140 mEq/L) or hypotonic fluids (hypotonic group, NaCl <100 mEq/L). Electrolyte blood concentration, glycaemia, and blood pressure were measured at 0, 6, and 24 hrs after the beginning of fluid therapy. Plasma creatinine, urine specific gravity, and urine electrolyte concentration were measured at 6 hrs. Standard intention-to-treat analysis and Bayesian analysis were conducted to assess the probability of hyponatremia and hypernatremia in each group. RESULTS: At the time of admission to hospital, no differences in natremia or the percentage of hyponatremia were found between groups. At 24 hrs, the percentage of hyponatremia in the hypotonic group was 20.6% as opposed to 5.1% in the isotonic group (p = 0.02). No differences in the number of adverse events other than hyponatremia were observed between groups. CONCLUSIONS: The use of hypotonic fluids increases the risk of hyponatremia when compared with isotonic fluids at 24 hrs following infusion (number needed to harm [confidence interval 95%] = 7[4;25]). In our sample, the use of isotonic fluids did not increase the incidence of adverse events compared with hypotonic fluids.

[The behavior of visceral proteins in digestive surgery patients undergoing total peripheral parenteral nutrition enriched with branched-chain amino acids (BCAA)]. / Comportamiento de las proteínas viscerales en enfermos quirúrgicos de aparato digestivo, sometidos a una nutrición parenteral periférica completa enriquecida con aminoácidos de cadena ramificada (AACR).

The objective of this study, is to confirm a clear benefit of protein synthesis after administration of branched amino acids in parenteral nutrition solutions. Particularly, on a parenteral total hypocaloric nutrition including lipids. Eighty one digestive surgical patients, were included in this study. Fifty with neoplastic disease and thirty one without. Patients in both study groups received a similar peripheral vein nutritional support regimen one week after surgical treatment. To evaluate the effects of the branched chain amino acid enrichment on total parenteral nutrition, we observed the behavior of short middle life proteins such as transferrin, prealbumin, and retinol binding protein, for their reliability as indexes of protein synthesis.

[Effects of branched-chain amino acids (BCAA) in complete hypocaloric nutrition of surgical patients with neoplasms of the digestive tract]. / Efecto de los aminoácidos de cadena ramificada (AACR) a través de nutriciones hipocalóricas completas en pacientes quirúrgicos con neoplasias de aparato digestivo.

One of the generic indications of parenteral peripheral malnutrition is the immediate postoperative period following surgery of the digestive tract. In the series presented, fifty patients with digestive neoplasia of different locations were studied, with slight or moderate malnutrition upon admittance. After the operation, feeding was done using hypocaloric parenteral solutions for the first seven days of the postop. period. In the qualitative intake of nitrogen in this type of nutrition, branched chain amino acids are important due to their beneficial effects on metabolism, and for this reason two complete hypocaloric solutions containing 45% and 15.5% of these amino acids were administered to each respective group under study. To justify the effect of improving the proteic synthesis attributed to these amino acids, the levels of rapid turnover proteins, transferrin, prealbumin and retinol-binding protein were determined.

[Acute pancreatitis associated with duodenal immunoblastic sarcoma and upper digestive hemorrhage]. / Pancreatitis aguda asociada a sarcoma inmunoblástico duodenal y hemorragia digestiva alta.

We present a patient with acute pancreatitis that was specially persistent from a biochemical viewpoint, derived from a duodenal sarcomatous tumor of immunoblastic type that narrowed the second duodenal segment for a length of about 8 centimeters. We discuss the possible role of tumoral neoformations in the production of pancreatitis due to increased intraluminal pressure distal to the Vater ampulla, or to occlusion of the Oddi sphincter or the Wirsung duct. We review the existent literature.

Presion arterial durante el embarazo normal. / Blood pressure during normal pregnancy

Se obtuvieron prospectivamente, mediante el empleo de una tecnica estandarizada de medida, 502 presiones arteriales de 42 gestantes sin patologia conocida. Se describe la presion arterial sistolica y diastolica en funcion de la edad gestacional. Se realizo una correlacion lineal entre amenorrea y ambas presiones arteriales, tomandose los pares de valores para cada gestante mediante una seleccion aleatoria. Los resultados mostraron ausencia de correlacion (r: 0.14 y 0.28; p > 0.05) por lo que se construyeron estimadores unicos de posicion y dispersion aplicables durante todo el embarazo. El limite superior (percentilo 95) para la presion sistolica fue 140 mm Hg y para la diastolica de 90 mm Hg, los inferiores (percentilo 5) 95 mm Hg para la sistolica y 55 mm Hg para la diastolica. Estos limites adquieren mayor importancia en aquellas mujeres que desconocen sus valores tensionales pregravidicos y por lo tanto es imposible conocer si estos se han incrementado

Presion arterial durante el embarazo normal. / Blood pressure during normal pregnancy

Se obtuvieron prospectivamente, mediante el empleo de una tecnica estandarizada de medida, 502 presiones arteriales de 42 gestantes sin patologia conocida. Se describe la presion arterial sistolica y diastolica en funcion de la edad gestacional. Se realizo una correlacion lineal entre amenorrea y ambas presiones arteriales, tomandose los pares de valores para cada gestante mediante una seleccion aleatoria. Los resultados mostraron ausencia de correlacion (r: 0.14 y 0.28; p > 0.05) por lo que se construyeron estimadores unicos de posicion y dispersion aplicables durante todo el embarazo. El limite superior (percentilo 95) para la presion sistolica fue 140 mm Hg y para la diastolica de 90 mm Hg, los inferiores (percentilo 5) 95 mm Hg para la sistolica y 55 mm Hg para la diastolica. Estos limites adquieren mayor importancia en aquellas mujeres que desconocen sus valores tensionales pregravidicos y por lo tanto es imposible conocer si estos se han incrementado