Background: Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined. Objective: To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate. Methods: The authors studied the effect of a custom pectin-based supplement in 6 subjects (3 male/3 female) aged 29-67 years with jejunocolonic anastomosis, 4 of whom required long-term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured. Results: Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short-chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, non-starch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (-5.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. Conclusion : Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although soluble fiber intake also enhances colonic SCFA production.

L’infection chronique par Helicobacter pylori touche plus de la moitié de la population mondiale et est la principale cause connue de l’adénocarcinome gastrique. La metformine, un antidiabétique oral, est de plus en plus étudiée pour ses propriétés antitumorales dans de nombreux types de cancers. Cependant, ses effets potentiels ont très peu été étudiés dans le cancer gastrique. Des expériences réalisées sur des lignées cellulaires cancéreuses gastriques et des tumeurs de patients amplifiées par xénogreffe chez la souris (PDX), ont permis de confirmer les propriétés antitumorales de la metformine. La metformine, en traitement préventif et curatif, diminue la capacité de formation des tumorsphères, l’expression des marqueurs de CSC gastriques, et la capacité d’auto-renouvellement propre aux CSC. Dans un second temps, nous avons montré que la metformine est capable d’inhiber la croissance bactérienne de H. pylori invitro et in vivo. Enfin, les effets de l’infection par H. pylori ont été étudiés sur la voie de signalisation mTOR par la réalisation d’une analyse transcriptomique et de western-blots sur des lignées cellulaires gastriques. Ceci a permis de démontrer que H. pylori inhibe le complexe mTORC1.Pour conclure, ce travail de thèse a permis i) de démontrer la capacité de la metformine à cibler les CSC gastriques, ii) de découvrir une nouvelle propriété antibactérienne de la metformine vis-à-vis de H. pylori, iii) de démontrer que H. pylori inhibe la voie de signalisation mTOR. / Chronic infection with Helicobacter pylori affects more than half of the world's population and is the main known cause of gastric adenocarcinoma. Metformin is an oral antidiabetic drug used to treat type 2 diabetes patients, and is being increasingly studied for its antitumoral properties in several cancer types. However, its potential effects in gastric cancer have not been thoroughly studied. Experiments performed on gastric cancer cell lines and patient-derived gastric carcinoma xenografts (PDX), have confirmed the antitumoral properties of metformin. Metformin, in preventive and curative treatment, decreases the tumorsphere formation, the expression of gastric CSC markers and the self-renewal capacity of CSC. In a second time, we have shown that metformin is able to inhibit the bacterial growth of H. pylori in vitro and in vivo. Finally, the effects of the H. pylori infection have been studied on the mTOR signaling pathway using a transcriptomic analysis and western blots, performed on gastric cancer cell lines. These show the ability of H. pylori to inhibit mTORC1.To conclude, this thesis work allowed i) to demonstrate the ability of metformin to target gastric CSCs, ii) to discover a new antimicrobial property of metformin against H. pylori, iii) to demonstrate that H. pylori inhibits the mTOR signaling pathway.

INTRODUCTION: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. MATERIALS AND METHODS: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. RESULTS: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). CONCLUSIONS: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients. / Revisión por pares

Background: Novel intraoperative imaging techniques, namely, hyperspectral (HSI) and fluorescence imaging (FI), are promising with respect to reducing severe postoperative complications, thus increasing patient safety. Both tools have already been used to evaluate perfusion of the gastric conduit after esophagectomy and before anastomosis. To our knowledge, this is the first study evaluating both modalities simultaneously during esophagectomy. Methods: In our pilot study, 13 patients, who underwent Ivor Lewis esophagectomy and gastric conduit reconstruction, were analyzed prospectively. HSI and FI were recorded before establishing the anastomosis in order to determine its optimum position. Results: No anastomotic leak occurred during this pilot study. In five patients, the imaging methods resulted in a more peripheral adaptation of the anastomosis. There were no significant differences between the two imaging tools, and no adverse events due to the imaging methods or indocyanine green (ICG) injection occurred. Conclusions: Simultaneous intraoperative application of both modalities was feasible and not time consuming. They are complementary with regard to the ideal anastomotic position and may contribute to better surgical outcomes. The impact of their simultaneous application will be proven in consecutive prospective trials with a large patient cohort.

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<p>Background: The objective of this thesis was to examine the role of psychosocial factors in weight loss success after bariatric surgery. It was proposed that a higher pre-operative body mass index (BMI), greater weight, depression, low self-esteem, and a childhood history of sexual abuse (CSA) would predict poor outcomes one year after Roux-en-y gastric bypass as evidenced by a BMI > 35 kg/m²and a lower percent total weight loss (%TWL). Methods: We administered a battery of psychological screening tools, including the Beck Depression Inventory-II, the Rosenberg Self-Esteem Scale and a self-report measure assessing CSA, to 262 patients seeking bariatric surgery at St. Joseph's Healthcare Hamilton. Patients completed the questionnaires prior to surgery and again one year post-surgery. Results: On average patients (n = 79) achieved good weight loss outcomes (BMI = 32.8 kg/m²) at one-year follow-up. Through multiple regression analysis we found that pre-operative BMI accounted for a significant proportion of variance in postoperative BMI [<em>R²</em> = .60, <em>F</em>(1, 77) = 114.4, <em>p</em> < .001]. Weight before surgery, however, did not predict %TWL after surgery. None of the psychosocial variables significantly predicted post-operative BMI or weight loss. These results are preliminary and are limited by the fact that participants did not present with clinically significant symptomatology and those with active psychopathology were excluded as suitable surgical candidates. Conclusion: These findings indicate that pre-operative BMI is a significant predictor of BMI one year after bariatric surgery, suggesting that more attention should be directed toward managing pre-operative BMI for heavier patients.</p> / Master of Science (MSc)

Objetivo: Determinar la frecuencia de Helicobacter pylori en muestras histopatológicas gástricas malignas y premalignas del servicio de anatomía patológica del Hospital Regional Lambayeque durante los años 2016 al 2019. Material y métodos. Estudio censal, observacional descriptivo, retrospectivo y transversal. La población de estudio estuvo conformada por los pacientes cuyas muestras histológicas gástricas fueron recibidas y estudiadas en el servicio de anatomía patológica del Hospital Regional Lambayeque. Resultados. Cumplieron con los criterios de selección 566 pacientes. La edad media fue 57,3; rango de 8 a 97 años. Hubo un predominio de pacientes entre la quinta (23.9%), sexta (24%) y séptima (17%) década de la vida. La frecuencia global de Helicobacter Pylori en las muestras seleccionadas fueron de 70.5%, con un predominio en el sexo masculino (71.2%). Los hallazgos anatomopatológicos se distribuyeron de la siguiente manera: 147 pacientes (26%) con gastritis crónica atrófica (GCA), 333 (58.8%) con metaplasia intestinal (MI), 60 (10.6%) con displasia y 26 (4.6%) con cáncer gástrico. Metaplasia intestinal fue el hallazgo más común; el mismo que se encontró en 166 personas (49.85%) con MI completa, 73 (21.92%) con MI incompleta y 94 (28.22%) con MI mixta. Conclusiones La frecuencia de Helicobacter Pylori (HP) fue alta en las lesiones premalignas, mientras que no hubo diferencias en la presencia o ausencia en muestras gástricas malignas. Conforme avanzaba la edad disminuía la frecuencia del HP pero aumentaban la gravedad de las lesiones. / Objective: Determine the frequency of Helicobacter pylori in malignant and premalignant gastric histopathological samples from the pathological anatomy service of the Hospital Regional Lambayeque during the years 2016 to 2019. Material and methods. Census, observational, descriptive, retrospective and cross-sectional study. The study population was made up of patients whose gastric histological samples were received and studied in the pathological anatomy service of the Hospital Regional Lambayeque. Results. 566 patients fulfilled the selection criteria. The mean age was 57.3; range from 8 to 97 years. There was a predominance of patients between the fifth (23.9%), sixth (24%) and seventh (17%) decades of life. The overall frequency of Helicobacter Pylori in the selected samples was 70.5%, with a predominance in the male sex (71.2%). The anatomopathological findings were distributed as follows: 147 patients (26%) with chronic atrophic gastritis (CAG), 333 (58.8%) with intestinal metaplasia (IM), 60 (10.6%) with dysplasia and 26 (4.6%) with gastric cancer. Intestinal metaplasia was the most common finding; the same that was found in 166 people (49.85%) with complete MI, 73 (21.92%) with incomplete MI and 94 (28.22%) with mixed MI. Conclusions The frequency of Helicobacter Pylori (HP) was high in premalignant lesions, while there were no differences in the presence or absence in malignant gastric samples. As age advanced, the frequency of PH decreased but the severity of the lesions increased.

Gastric cancer ranks the fifth most common and third leading cause of cancer‐related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGFβ, NOTCH, and NFκB signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS‐activated (KrasG12D, Tp53R172H), a WNT‐activated (Apcfl/fl, Tp53R172H), and a diffuse (Cdh1fl/fl, Apcfl/fl) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient‐derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients.