Congenital esophageal stenosis: a rare malformation of the foregut.

Congenital esophageal stenosis (CES) is a type of esophageal stenosis, and three histological subtypes (tracheobronchial remnants, fibromuscular thickening or fibromuscular stenosis, and membranous webbing or esophageal membrane) are described. Symptoms of CES usually appears with the introduction of the semisolid alimentation. Dysphagia is the most common symptom, but esophageal food impaction, respiratory distress or failure to thrive can be clinical manifestations of CES. Wide spectrum of differential diagnoses leads to delayed definitive diagnosis and appropriate treatment. Depends on hystological subtype of CES, some treatment procedures (dilation or segmental esophageal resection) are recommended, but individually approach is still important in terms of frequency and type of dilation procedures or type of the surgical treatment. Dysphagia can persist after the treatment and a long follow-up period is recommended. In 33% of patients with CES, a different malformations in the digestive system, but also in the other systems, are described.

Interplay between STAT3, Cell Adhesion Molecules and Angiogenesis-Related Parameters in Gastric Carcinoma. Does STAT3 Really Have a Prognostic Value?

Background and objectives: Gastric cancer (GC) is one of the deadliest malignancies, with the underlying pathophysiological mechanisms still not completely understood. In this study, we aimed to investigate the signal transducer and activator of transcription 3 (STAT3) moleculeconnection with the pathological features of GCs, and the expression of cell adhesive molecules (E-cadherin and ß-catenin) and angiogenesis-related factors (vascular endothelial growth factor (VEGF), HIF1α, and CD31)). Materials and Methods: This study comprised 136 cases of GCs with data related to the patients' demographic characteristics (age, gender) and pathological features (tumor location, gross type, Laurens' type of GC, histological differentiation, invasion depth, lymphovascular invasion and the presence of metastases) which were correlated with STAT3 expression. Additionally, STAT3 expression and the expression of adhesive molecules and angiogenesis-related factors were studied by immunohistochemical methods. Results: The expression of STAT3 was found to be significantly associated with the occurrence of poorly differentiated GCs in the lower portion of the stomach and with the presence of distant metastases. Interestingly, none of the investigated parameters related to cell adhesion or to angiogenesis were found to be related to the expression of STAT3. Conclusions: The lack of significant differences between the studied STAT3 expression and some of the molecules associated with different cancer features might be due to the characteristics of the studied population sample associated with the origin, heterogeneity, and cancer pathophysiological background. Nonetheless, the results of our study suggest that STAT3 could be a useful marker for the presence of distant GC metastases, which further indicates that STAT3 action might involve some other signaling molecules/pathways that warrant further elucidation.

Low dose of carvacrol prevents rat pancreas tissue damage after L-arginine application, while higher doses cause pancreatic tissue impairment.

Carvacrol (5-isopropyl-2-methylphenol) is a biologically active monoterpene phenol abundantly present in the essential oils of many Lamiaceae aromatic/ethnomedicinal plants. Herein, we aimed to evaluate the damaging effect of carvacrol to rat pancreatic tissue, but also to assess its possible ameliorative impact on pancreatic damage induced by L-arginine. The toxic and beneficial (in a dose of 10 mg/kg) properties of carvacrol were assessed by measuring serum α-amylase and lipase activities, tissue malondialdehyde (MDA) content, and pathohistological changes in pancreatic tissue. Application of 100/500 mg/kg of carvacrol produced a significant increase in α-amylase activity, followed by inflammatory-cell infiltration and patchy interlobular edema in the pancreas. In the L-arginine-induced pancreatitis model, a dose of 10 mg/kg of carvacrol prevented an increase in α-amylase and lipase activities, and MDA formation, when compared to the animals that received L-arginine only. Animals treated with carvacrol prior to L-arginine administration displayed mild edema and inflammatory infiltration with few necrotic areas. Contrary to that, animals that received only L-arginine showed a massive leukocyte infiltrate with edema and substantial necrotic areas. In our study carvacrol showed significant protective effects and a potential to modulate leukocyte recruitment in pancreatic tissue after L-arginine injection.

Comparison between the effects of selenomethionine and S-adenosylmethionine in preventing cholestasis-induced rat liver damage.

We aimed to evaluate whether two methionine-related compounds, S-adenosylmethionine (SAM), and selenomethionine (SM), could lessen liver damage induced by regurgitated bile in a model of rat bile duct ligation (BDL). Hepatoprotective potentials of S-adenosylmethionine and selenomethionine were estimated based on the changes of serum liver damage parameters (aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and lactate dehydrogenase activity, and bilirubin concentration), tissue oxidative [xanthine oxidase (XO) and catalase activity, thiobarbituric acid reactive substances (TBARS) levels] and inflammatory [tumor necrosis factor-alfa (TNF-α) concentration] parameters, and morphological liver tissue alterations that follow cholestasis. The treatment regimens proved themselves able to prevent significant liver damage induced by cholestasis. Both SAM and SM decreased XO activity and TBARS levels and increased catalase activity, while only SM significantly reduced TNF-α concentration. Morphological changes related to bile-induced liver damage were also found to be partially diminished by SAM and SM. In view of the mechanisms of action of the two tested methionine-derived compounds, one might say that SM predominantly acted as an antioxidant, while SAM exerted its activity by potentially modulating different gene expression and protein structures. It is also worth mentioning that this is the first study (to the best of our knowledge) that dealt with the effects of SM on BDL-induced liver injury in rats and of the findings that speak favorably of this powerful antioxidant.

Exogenous putrescine affects polyamine and arginine metabolism in rat liver following bile ductus ligation.

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines' concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.

The anesthetic action of some polyhalogenated ethers-Monte Carlo method based QSAR study.

Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development. To investigate the aspects of their anesthetic, QSAR models based on the Monte Carlo method were developed for a set of polyhalogenated ethers. Until now, their anesthetic action has not been completely defined, although some hypotheses have been suggested. Therefore, a QSAR model should be developed on molecular fragments that contribute to anesthetic action. QSAR models were built on the basis of optimal molecular descriptors based on the SMILES notation and local graph invariants, whereas the Monte Carlo optimization method with three random splits into the training and test set was applied for model development. Different methods, including novel Index of ideality correlation, were applied for the determination of the robustness of the model and its predictive potential. The Monte Carlo optimization process was capable of being an efficient in silico tool for building up a robust model of good statistical quality. Molecular fragments which have both positive and negative influence on anesthetic action were determined. The presented study can be useful in the search for novel anesthetics.

Pre- vs. post-treatment with melatonin in CCl4-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies.

AIMS: The present study was designed to compare the ameliorating potential of pre- and post-treatments with melatonin, a potent natural antioxidant, in the carbon tetrachloride-induced rat liver damage model by tracking changes in enzymatic and non-enzymatic liver tissue defense parameters, as well as in the occurring pathohistological changes. MAIN METHODS: Rats from two experimental groups were treated with melatonin before and after CCl4 administration, while the controls, negative and positive, received vehicle/melatonin and CCl4, respectively. Serum levels of transaminases, alkaline phosphates, γ-GT, bilirubin, and albumin, as well as a wide panel of oxidative stress-related parameters in liver tissue, were determined in all experimental animals. Liver tissue specimens were stained with hematoxylin and eosin and further evaluated for morphological changes. KEY FINDINGS: Both pre- and post-treatment with melatonin prevented a CCl4-induced increase in serum (ALT, AST, and γ-GT) and tissue (MDA and XO) liver damage markers and a decrease in the tissue total antioxidant capacity, in both enzymatic and non-enzymatic systems. The intensity of pathological changes, hepatocyte vacuolar degeneration, necrosis and inflammatory cell infiltration, was suppressed by the treatment with melatonin. SIGNIFICANCE: In conclusion, melatonin, especially as a post-intoxication treatment, attenuated CCl4-induced liver oxidative damage, increased liver antioxidant capacities and improved liver microscopic appearance. The results are of interest due to the great protective potential of melatonin that was even demonstrated to be stronger if applied after the tissue damage.

[Analysis of the grade of esophagitis, chromendoscopical and histological findings of esophagus in patients with gastroesophageal reflux disease before and after the therapy].

BACKGROUND/AIM: The symptoms of gastroesophageal reflux disease (GERD) are among the most common complaints for which patients are indicated for visiting gastroenterologist. It occurs as a result of the effect made by gastric reflux contents that moves into the esophagus. The prevalence of all forms of GERD is 40%. The aim of this study was to analyze the grade of esophagitis, chromendoscopical and histological findings of esophagus in patients with GERD before and after the therapy. METHODS: A prospective study included 90 patients with symptoms of GERD, divided into 2 groups depending on whether they had endoscopic signs of gastroezophageal reflux (group ERD), or not (group NERD). All the patients had esophagogastroduodenoscopy, chromoendoscopy staining, test for Helicobacter pylori and histological findings of the esophagus. In the patients with Helicobacter pylori infection eradication therapy was done. RESULTS: Esophagitis-B level was present in most of the patients. Among the groups, roughly the same number responded to positive findings on chromoendoscopy. After the therapy, chromoendoscopy was significantly negative in both groups of the patients comparing to chromoendoscopy before the therapy (p = 0.00001). Multiplication and elongation of papilla, basal cell hyperplasia, vascular dilatation, increasing of mitotic activity and the presence of polymorphonuclear leukocyte cells were statistically more frequent histological findings in the group ERB compared to the group NERB. After the therapy, the patients in both groups had statistically less histological findings of appropriate esophageal parameters. CONCLUSION: Chromoendoscopy combined with the standard endoscopy increases the sensitivity and specificity for reflux disease. Histology in the reflux disease is associated with endoscopic and clinical findings so that the localization of taking biopsies and histological criteria of pathohistological changes must be clearly defined. Multiplication and elongation of papilla, basal cell hyperplasia and the presence of polymorphonuclear leukocytes are the most relevant criteria in the diagnosis NERD.

The model for the end-stage liver disease and Child-Pugh score in predicting prognosis in patients with liver cirrhosis and esophageal variceal bleeding.

BACKGROUND/AIM: Esophageal variceal bleeding is one of the most frequent and gravest complications of liver cirrhosis, directly life-threatening. By monitoring certain clinical and laboratory hepatocellular insufficiency parameters (Child-Pugh score), it is possible to determine prognosis in patients who are bleeding and evaluate further therapy. Recently, the Model for the End-Stage Liver Disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. The aim of the study was to evaluate survival prognosis of cirrhotic patients by the MELD and Child-Pugh scores and to analyze the MELD score prognostic value in patients with both liver cirrhosis and variceal bleeding. METHODS: We retrospectively evaluated the survival rate of a group of 100 cirrhotic patients of a median age of 57 years. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. We also analysed clinical and laboratory hepatocellular insufficiency parameters in order to examine their connection with a 15-month survival. The MELD values were correlated with the Child-Pugh scores. The Student's t-test was used for statistical analysis. RESULTS: Twenty-two patients died within 15-months followup. Age and gender did not affect survival rate. The Child-Pugh and MELD scores, as well as ascites and encephalopathy significantly differed between the patients who survived and those who died (p < 0.0001). The International Normalized Ratio (INR) values, serum creatinine and bilirubin were significantly higher, and albumin significantly lower in the patients who died (p < 0.0001). The MELD score was significantly higher in the group of patients who died due to esophageal variceal bleeding (p < 0.0001). CONCLUSION: In cirrhotic patients the MELD score is an excellent survival predictor at least as well as the Child-Pugh score. Increase in the MELD score is associated with decrease in residual liver function. In the group of patients with liver cirrhosis and esophageal variceal bleeding, the MELD score identifies those with a higher intrahospital mortality risk.

[Risk and causes of gastroesophageal bleeding in patients with liver cirrhosis].

BACKGROUND/AIM: Variceal bleeding is the most life-threating complication in liver cirrhosis. The aim of this study was to analyze the sources of gastroesophageal bleeding in patients with liver cirrhosis and to ascertain the risk factors of bleeding from esophageal varices. METHODS: This prospective study included 52 patients with liver cirrhosis and portal hypertension. Severity of liver dysfunction according to Child's classification, coagulation parameters, and endoscopic findings were analyzed. In patients with varices we analyzed the size, color, location of varices, and the presence of red signs. The varices were classified as small, medium and large. RESULTS: Esophageal varices were found in 76.9% of the patients. Isolated varices were present in 36.6%, and associated with other findings in 40.3%. Small varices were present in 10%, medium in 25% and large in 65% patients. Of them 55% had variceal bleeding. Variceal bleeding was present in 50% of the patients with medium and in 65.38% of the patients with large varices. There was no bleeding in the patients with small varices. Endoscopy revealed red signs before bleeding in 85% of the patients with large varices. There was a higher incidence of variceal bleeding in the Child's group B. There were no significant differences (p > 0.05) in the coagulation parameters in patients with and without variceal bleeding. Rebleeding was present in 86.36% of the patients. Most of them (52.63%) were rebleeding between 7 weeks and 12 months after the first episode of variceal bleeding. In the patients with the most severe hepatocellular dysfunction (Child's group C) the period between the first bleeding and rebleeding was the shortest (mean, 20.8 days). CONCLUSION: Our study revealed that esophageal varices are the most frequent sources of bleeding in the patients with liver cirrhosis. There is the association between the first bleeding and large varices and the red signs. Coagulation disorders and hepatic dysfunction were not related to the initial episode of variceal bleeding. The risk of early rebleeding was higher in the patients with severe hepatic dysfunction (Child's class C).