Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence.

BACKGROUND: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. METHOD: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995-2010 and 2010-2020). RESULTS: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. CONCLUSIONS: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

T3-T4 index as a prognostic marker of response to biological treatments in elderly patients with inflammatory bowel disease.

Following the growing trend of trying to individualise treatment in inflammatory bowel disease and in view of the challenge posed by elderly patients requiring biologic treatments, we have conducted a study in our centre to assess the T3/T4 index as a predictor of response to biologic treatments in elderly patients.

Experience in the treatment of obstructive colorectal cancer with self-expandable colon prosthesis in a tertiary hospital.

Colorectal cancer is one of the most frequent neoplasms, with an increasing incidence in recent years. Intestinal obstruction is present at the time of diagnosis in 10-30% of patients. The aim of our study is to describe our experience in the use of colonic SEMS in the treatment of colonic stenosing neoplasia. For this purpose, we retrospectively evaluated the 92 patients treated with self-expandable metallic prostheses in our hospital between 2016 and 2021. In 66.3% of patients the prosthesis placement was bridge to curative surgery and in 33.7% with palliative attitude. The stenosis location was differentiated: rectum (2.1%), rectosigmoid junction (20.7%), sigma (58.7%), left colon (8.7%), splenic angle (8.7%) and transverse colon (1.1%); being the size of the self-expandable metallic prostheses used 60x25 mm, 90x25 mm and 120x25 mm. The procedure was technically effective in 92.4% of the cases and clinically effective in 89.1%, with post-procedural perforations being detected in 9 patients (9.8%). Survival 30 days after prosthesis placement was 91.3%. No mortality directly related to the procedure was detected. In our experience, placement of self-expandable metallic prostheses is a safe and effective option in the initial management of neoplastic colon stenosis.

Experience in the treatment of esophageal anastomosis dehiscence using self-expanding metallic prosthesis.

INTRODUCTION: esophageal anastomosis dehiscence is a serious complication after esophageal cancer surgery with high mortality risk. One of the treatment options is self-expanding esophageal prostheses. Our aim was to evaluate the outcome of esophageal prostheses in the management of suture dehiscences after oncologic surgery. MATERIAL AND METHODS: we performed a descriptive and retrospective study with patients diagnosed with esophageal anastomosis fistula or dehiscence treated by esophageal prosthesis between the years 2015 and 2021. We considered technical success as the correct positioning of the prosthesis with visualization of anastomotic leak closure after release of the prosthesis during endoscopy, and clinical success the resolution of dehiscence after removal of the prosthesis 8 weeks after positioning. RESULTS: technical success was 95% and clinical success 89%. CONCLUSION: in our center, esophageal prostheses are a treatment option for fistulas and anastomotic dehiscence after surgery with a high success rate and few complications.

Experience with ustekinumab in reservoir Crohn's disease.

Crohn's disease of the reservoir is a pathology of difficult diagnosis and complex approach due to the scarce documented evidence on it. Recently, studies have been published on the treatment strategies available for this entity. Based on the above, we have analyzed the experience of our center in the treatment of reservoir Crohn's disease with one of the new biologic agents, ustekinumab.

A further step in the differential diagnosis of refractory abdominal pain: cryptogenic multifocal ulcerous stenosing enteritis.

We present the case of a 45-year-old male smoker, who presented with intermittent abdominal pain related to intake since one year previously. During the study, positive anti-transglutaminase antibodies were detected, leading to a diagnosis of celiac disease, with no improvement of the clinical symptoms despite total suspension of gluten. The study was completed by magnetic resonance (MR) enterography, detecting extensive and ill-defined inflammatory alterations in the jejunum and proximal ileum walls.

A conceptual framework for the collection of food products in a Total Diet Study.

A total diet study (TDS) provides representative and realistic data for assessing the dietary intake of chemicals, such as contaminants and residues, and nutrients, at a population level. Reproducing the diet through collection of customarily consumed foods and their preparation as habitually eaten is crucial to ensure representativeness, i.e., all relevant foods are included and all potential dietary sources of the substances investigated are captured. Having this in mind, a conceptual framework for building a relevant food-shopping list was developed as a research task in the European Union's 7th Framework Program project, 'Total Diet Study Exposure' (TDS-Exposure), aimed at standardising methods for food sampling, analyses, exposure assessment calculations and modelling, priority foods, and selection of chemical contaminants. A stepwise approach following the knowledge translation (KT) model for concept analysis is proposed to set up a general protocol for the collection of food products in a TDS in terms of steps (characterisation of the food list, development of the food-shopping list, food products collection) and pillars (background documentation, procedures, and tools). A simple model for structuring the information in a way to support the implementation of the process, by presenting relevant datasets, forms to store inherent information, and folders to record the results is also proposed. Reproducibility of the process and possibility to exploit the gathered information are two main features of such a system for future applications.

[Macronutrients, food intake and body weight; the role of fat]. / Macronutrientes, ingesta de alimentos y peso corporal; papel de la grasa.

INTRODUCTION: "Globesity" is the term that the World Health Organization (WHO) employs to define the growth of obesity in the world from the last 40 years which started in the developed countries and has been inevitably propagated to the developing ones. Governments and international organizations are aware of the problem and they are trying to implement measures to fight it. AIM: To analyze the current evidence in terms of studies about the relationship between macronutrients (especially fat and lipid release systems) and the secretion of gastrointestinal peptides that are involved with satiety and satiation. METHODS: The search was conducted in Medline (via Pubmed) using different combinations of MeSH terms and in the database LILACs using "DeCS". A selection of another articles relevant to the review topic was also examined. RESULTS AND DISCUSSION: At present, there are several laboratories and industries developing novel bioactive ingredients aimed at the regulation of food intake, with emphasis on those related with fat intake and the different ways in which fat can be technologically processed in order to create structures able to enhance satiety and/ or diminish hunger. CONCLUSION: These ingredients will be the future of functional foods focused on the prevention of weight gain and the support of other strategies against obesity (dietary, behavioral, etc…).

Introducción: "Globesity" es el término que la Organización Mundial de la Salud (OMS) emplea para denominar el progresivo aumento de la obesidad experimentado desde los últimos 40 años en los países desarrollados y cuyo contagio a los países en vías de desarrollo ha sido inevitable. Esta situación ha llevado a los gobiernos y organizaciones internacionales de todo el mundo a plantear estrategias destinadas a frenar dicha epidemia. Objetivo: Recopilar los conocimientos más actuales que se tienen de la relación entre los macronutrientes (en especial de la grasa y los sistemas de liberación de lípidos) y la secreción de péptidos gastrointestinales relacionados con la saciedad y saciación. Metodología: Se realizó una búsqueda bibliográfica basada en la combinación de términos MeSH en Medline (vía PubMed) y en LILACs mediante DeCS, así como una selección de otros artículos relacionados con la temática de la revisión. Resultados y discusión: Actualmente, numerosos laboratorios públicos y privados se encuentran investigando diversos ingredientes bioactivos relacionados con la regulación del apetito. Destacan los relacionados con la grasa ingerida y la forma en que esta puede ser tratada físicamente, sobre todo emulsiones y estructuras parecidas y su influencia sobre la saciedad y/o disminución de la sensación de hambre. Conclusiones: Estos ingredientes alimentarios se plantean como el futuro de los alimentos funcionales enfocados a la prevención de la ganancia de peso y ayuda a otras estrategias contra la obesidad (alimentarias, conductuales, etc...).

Effect of hydrogen peroxide on secretory response, calcium mobilisation and caspase-3 activity in the isolated rat parotid gland.

The parotid glands are highly active secretory systems subjected to continuous stress, which in turn, can lead to several pathophysiological conditions. Damage of the parotid glands are caused by radical oxygen species (ROS) as by-products of oxygen metabolism. This study investigated the effect of hydrogen peroxide (H(2)O(2)) on Carbachol (CCh)-evoked secretory responses and caspase-3 activity in the isolated rat parotid gland to understand the role of oxidative stress on the function of the gland. Amylase secretion, cytosolic calcium concentration ([Ca(2+)](i)) and caspase-3 activity in parotid gland tissue were measured using fluorimetric methods. H(2)O(2) had little or no effect on amylase secretion compared to basal level. Combining H(2)O(2) with CCh resulted in an attenuation of the CCh-evoked amylase secretion compared to the effect of CCh alone. CCh can evoke a large increase in [Ca(2+)](i) comprising an initial peak followed by a plateau. In a Ca(2+)-free medium containing 1 mM EGTA, CCh evoked only the initial peak of [Ca(2+)](i). H(2)O(2) alone evoked a gradual and dose-dependent increase in [Ca(2+)](i). Combining H(2)O(2) with CCh resulted in a decrease in [Ca(2+)](i) compared to the effect of CCh alone. In a Ca(2+)-free medium, H(2)O(2) still evoked a small increase in [Ca(2+)](i), but this response was less compared to the results obtained with H(2)O(2) in normal [Ca(2+)](0). Combining H(2)O(2) with CCh resulted in only a small transient increase in [Ca(2+)](i). Following CCh stimulation, H(2)O(2) application resulted in a large increase in [Ca(2+)](i) in normal [Ca(2+)](0). This effect of H(2)O(2) was partially abolished in a nominally free Calcium medium containing EGTA. H(2)O(2) can stimulate caspase-3 activity in parotid gland tissue. Similar response was obtained with betulinic acid and thapsigargin (TPS) on caspase-3 activity compared to basal. The results have demonstrated that like CCh, H(2)O(2) can also mobilise Ca(2+) from intracellular stores and facilitate its influx into the cell from extracellular medium. This effect of H(2)O(2) may be due to its activity to induce apoptosis in the parotid gland, since H(2)O(2) can stimulate the activity of caspase-3, a marker of cellular apoptosis.

Magnesium-calcium signalling in rat parotid acinar cells: effects of acetylcholine.

This study investigated the effects of extracellular Mg(2+) ([Mg(2+)](o)) on basal and acetylcholine (ACh)-evoked amylase secretion and intracellular free Ca(2+) ([Ca(2+)](i)) in rat parotid acinar cells. In a medium containing 1.1 mM [Mg(2+)](o), ACh evoked significant increases in amylase secretion and [Ca(2+)](i). Either low (0 mM) or elevated (5 and 10 mM) [Mg(2+)](o) attenuated ACh-evoked responses. In a nominally Ca(2+) free medium, elevated [Mg(2+)](o) attenuated basal and ACh-evoked amylase secretion and [Ca(2+)](i). In parotid acinar cells incubated with either 0, 1.1, 5 or 10 mM [Mg(2+)](o), ACh evoked a gradual decrease in [Mg(2+)](i). These results indicate that the ACh-evoked Mg(2+) efflux is an active process since Mg(2+) has to move against its gradient. Either lidocaine, amiloride, N-methyl-D: -glucamine, quinidine, dinitrophenol or bumetanide can elevate [Mg(2+)](i) above basal level. In the presence of these membrane transport inhibitors, ACh still evoked a decrease in [Mg(2+)](i) but the response was less pronounced with either [Na(+)](o) removal or in the presence of either amiloride or quinidine. These results indicate marked interactions between Ca(2+) and Mg(2+) signalling in parotid acinar cells and that ACh-evoked Mg(2+) transport was not dependent upon [Na(+)](o).

Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced type 1 diabetes mellitus.

Diabetes mellitus (DM) is a major health problem at present affecting about 180 million people worldwide. DM is associated with many metabolic abnormalities in the body including the indigestion of carbohydrates leading to malnutrition and weight loss. In this article we investigate the cellular and molecular mechanisms of exocrine pancreatic insufficiency in streptozotocin (STZ, 60 mg kg(-1), i.p.)-induced DM in male rats compared to healthy age-matched controls. Either electrical field stimulation (EFS) or cholecystokinin octapeptide (CCK-8, 10(-8) M) can elicit large and significant (P < 0.05) increases in amylase output from pancreatic segments compared to basal secretion. Insulin (10(-6) M) alone has no significant effect on amylase output compared to basal but it enhanced the secretory responses to either EFS or CCK-8. When rats were rendered diabetic with STZ, either EFS or CCK-8-evoked amylase output was significantly (P < 0.01) decreased compared to the responses obtained with either EFS or CCK-8 alone in healthy age-matched control pancreas. In addition, CCK-8 can elicit large dose-dependent release of amylase in age-matched control and diabetic acinar cells with significantly (P < 0.05) reduced responses in diabetic acinar cells. CCK-8 evoked a large rapid increase in peak cytosolic free calcium concentration ([Ca2+]c) followed by a decrease to a plateau phase in age-matched control fura-2-loaded pancreatic acinar cells. These responses were significantly (P < 0.05) decreased in STZ-induced diabetic acinar cells. In the presence of 10(-6) M insulin, CCK-8 evoked a much larger increase in the Ca2+ transient compared to the response obtained with CCK-8 alone. These effects were significantly (P < 0.01) inhibited in STZ-induced diabetic acinar cells. Similarly, in zero extracellular Ca2+ [Ca2+]c, the CCK-8-evoked [Ca2+]c was significantly (P < 0.05) reduced in both diabetic and age-matched control acinar cells, but with more pronounced reduction in diabetic acinar cells. CCK(A) receptor mRNA levels remained unchanged in diabetic rat acinar cells compared to age-matched healthy control. In contrast, amylase mRNA was significantly (P < 0.05) reduced in diabetic acinar cells compared to control. The results indicate that reduced amylase secretion in response to either EFS or CCK-8 in the diabetic pancreas may be due to reduced [Ca2+]c and gene expression for amylase and not to the gene expression of CCK(A) receptor in pancreatic acinar cells.

Involvement of ryanodine-operated channels in tert-butylhydroperoxide-evoked Ca2+ mobilisation in pancreatic acinar cells.

Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis, a disease characterised in its earliest stages by disruption of intracellular Ca2+ homeostasis. The present study was carried out in order to establish the effect of the organic pro-oxidant, tert-butylhydroperoxide (tBHP), on the mobilisation of intracellular Ca2+ stores in isolated rat pancreatic acinar cells and the mechanisms underlying this effect. Cytosolic free Ca2+ concentrations ([Ca2+]c) were monitored using a digital microspectrofluorimetric system in fura-2 loaded cells. In the presence of normal extracellular Ca2+ concentrations ([Ca2+]o), perfusion of pancreatic acinar cells with 1 mmol l-1 tBHP caused a slow sustained increase in [Ca2+]c. This increase was also observed in a nominally Ca2+-free medium, indicating a release of Ca2+ from intracellular stores. Pretreatment of cells with tBHP abolished the typical Ca2+ response of both the physiological agonist CCK-8 (1 nmol l-1) and thapsigargin (TPS, 1 micromol l-1), an inhibitor of the SERCA pump, in the absence of extracellular Ca2+. Similar results were observed with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP, 0.5 micromol l-1), a mitochondrial uncoupler. In addition, depletion of either agonist-sensitive Ca2+ pools by CCK-8 or TPS or mitochondrial Ca2+ pools by FCCP were unable to prevent the tBHP-induced Ca2+ release. By contrast, simultaneous administration of TPS and FCCP clearly abolished the tBHP-induced Ca2+ release. These results show that tBHP releases Ca2+ from agonist-sensitive intracellular stores and from mitochondria. On the other hand, simultaneous application of FCCP and of 2-aminoethoxydiphenylborane (2-APB), a blocker of IP3-mediated Ca2+ release, was unable to suppress the increase in [Ca2+]c induced by tBHP, while the application of 50 micromol l-1 of ryanodine (which is able to block the ryanodine channels) inhibits tBHP-evoked Ca2+ mobilisation. These findings indicate that tBHP releases Ca2+ from non-mitochondrial Ca2+ pools through ryanodine channels.