Hyperspectral imaging (HSI) in abdominal surgery is a new non-invasive tool for the assessment of the perfusion and oxygenation of various tissues and organs. Its benefit in pancreatic surgery is still unknown. The aim of this study was to evaluate the key impact of using HSI during pancreatoduodenectomy (PD). In total, 20 consecutive patients were included. HSI was recorded during surgery as part of a pilot study approved by the local Ethics Committee. Data were collected prospectively with the TIVITA® Tissue System. Intraoperative HS images were recorded before and after gastroduodenal artery (GDA) clamping. We detected four patients with celiac artery stenosis (CAS) caused by a median arcuate ligament (MAL). In two of these patients, a reduction in liver oxygenation (StO2) was discovered 15 and 30 min after GDA clamping. The MAL was divided in these patients. HSI showed an improvement of liver StO2 after MAL division (from 61% to 73%) in one of these two patients. There was no obvious decrease in liver StO2 in the other two patients with CAS. HSI, as a non-invasive procedure, could be helpful in evaluating liver and gastric perfusion during PD, which might assist surgeons in choosing the best surgical approach and in improving patients’ outcomes.

No description available.

No description available.

<p>Abstract Redacted.</p> / Master of Science (MSc)

Background: Nutritional deficiencies are frequent in celiac disease (CeD), and one of the most common is zinc (Zn) deficiency. Supplements are often prescribed to treat Zn deficiency; however, they have been associated with adverse events and reduced absorption of other minerals. Data collected in our clinic showed that 38% of CeD patients would opt for a diet to improve Zn, however, such a diet may be challenging due to food interactions with phytic acid, which blocks Zn absorption. Therefore, the feasibility and efficacy of a Zn-optimized diet compared to supplementation is unknown. Aims: To assess the feasibility of the protocol and collect data on estimated effect sizes for secondary outcomes to plan a properly powered randomized controlled trial (RCT). Methods: We conducted an open-label, pilot RCT. CeD patients were randomized to Zn supplementation (Zn gluconate 25mg) or a Zn-optimized diet for 3 months and followed up with a 3-month pragmatic approach. We evaluated enrollment rates and adherence to both interventions. Plasma and urine Zn, stool samples, and questionnaires were collected pre- and post-intervention. Results: We enrolled 28 participants and 16 of them have completed the study. Interim analysis shows an enrollment fraction of 26% (i.e. 28/108 eligible participants), and a dropout rate of 17.9%. Eighty-two % of participants allocated to the Zn-supplement intervention and 50% in the dietary intervention were compliant at 3 months. Based on the effect size for normalization of plasma Zn at 3 months, 142 participants are required for an adequately powered RCT in the future. There were no significant differences in gastrointestinal or extra-intestinal symptoms, quality of life, anxiety and depression or adverse events between interventions. Conclusion: Based on this preliminary analysis, recruitment of participants will take 6 months longer than expected. Assessment of reasons for diet non-adherence will allow implementation of strategies to improve feasibility. / Thesis / Master of Science in Medical Sciences (MSMS)

Celiac disease is an autoimmune enteropathy driven by the ingestion of gluten in genetically predisposed individuals carrying HLA-DQ2 and/or -DQ8 genes. Currently, the only available treatment is a strict, life-long, gluten-free diet (GFD), which is very restrictive and not always effective, highlighting the need for alternative therapies. Celiac disease requires activation of both the innate (intraepithelial lymphocytes or IELs) and adaptive (lamina propria CD4+ T cells) arms of the immune system. Activation of these two pathways leads to the destruction of IEC and villous atrophy. Thus, IEC damage is a hallmark of CeD. However, IECs are not only the target of tissue damage; they also actively participate in CeD pathogenesis by translocating gluten peptides, expressing stress-induced markers, and releasing TG2 into the gut lumen to generate TG2-gluten complexes. Although IECs are known to express MHC, their role in gluten-dependent T cell activation has never been proven, partly because of the lack of an appropriate in vitro epithelial model expressing human MHC class II. This thesis aims to address this gap by developing a humanized organoid monolayer expressing the CeD risk gene HLA-DQ2.5, to investigate the interaction between IEC-gluten-T cells. The expression of epithelial MHC class II was evaluated in active and treated CeD patients, as well as in gluten-immunized and control (non-immunized; NI) DR3-DQ2.5 transgenic mice that express only CeD-associated MHC class II (HLA-DQ2.5). Active CeD patients and gluten-immunized DR3-DQ2.5 mice demonstrated higher expression of epithelial MHC class II compared with their treated and NI counterparts. Organoid monolayers developed from these mice and were treated with or without IFN-. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice showed higher expression of MHC class II compared with NI mice, and this expression was upregulated by IFN- treatment. The functional consequences of MHC class II expression were determined by co-culturing organoid monolayers with CD4+ T cells in the presence of gluten and zein (a non-gluten protein). In the co-culture, gluten, but not zein, enhanced CD4+ T cell proliferation, activation, and release of cytokines, including IL-2, IFN- and IL-15, in the co-culture supernatants. Bacteria have recently emerged as modulators of inflammation in patients with CeD. It has been shown that opportunistic pathogens, including Pseudomonas aeruginosa, partially metabolize gluten into more immunogenic peptides. As such, the role of bacterially modified gluten in modulating the T cell response was assessed using the in vitro co-culture system I described. For this, monolayers were treated with the gluten pre-digested, or not, by elastase-producing P. aeruginosa or its lasB mutant. Gluten metabolized by P. aeruginosa, but not by the lasB mutant, significantly increased CD4+ T cell responses. In conclusion, MHC class II-expressing organoid monolayers are a functional model that can promote T cell responses under certain conditions. The model described in this thesis reveals a new immunomodulatory role for IECs in activating CD4+ T cells through MHC class II. This mechanism may serve to localize and further increase injury to the epithelium caused by gluten-specific CD4+ T cells in CeD. Therefore, therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in CeD, providing an alternative or adjuvant therapy to the current GFD treatment. / Thesis / Doctor of Philosophy (PhD) / Celiac disease is one of the most common food sensitivities, affecting approximately 1 in 100 people worldwide, including Canada. It occurs in people with specific genes (DQ2 and/or DQ8) when they eat gluten-containing foods such as wheat, barley, and rye. In people with celiac disease the immune system overreacts to gluten, damaging the lining of the upper gut, which we call “epithelium. This lining of cells constitutes the first barrier between the external world and our body, allowing in healthy conditions for nutrients to be absorbed but blocking the passage of gut microbes, some of which can cause disease or worsen gut inflammation. In patients with celiac disease, gluten crosses the epithelium into the gut tissue, where it activates specific cells of the immune system called “T cells”. Recently, there has been growing interest in whether the gut lining itself plays a role in triggering this immune response in celiac disease, though this has not yet been proven. If proven, this would suggest that the gut lining is responsible for directing the harmful immune response to gluten and should be considered a target site when developing therapies to prevent or treat celiac disease. This concept has been difficult to prove because we do not have a model to investigate this question. Such a model would require a gut lining that carries the genes linked to celiac disease. My thesis describes the development of such a model, made of a gut lining from a mouse genetically modified to carry human celiac disease genes. Using this model, I found that when the gut lining was exposed to certain molecules present in celiac patients (cytokines), it switched on other molecules that ultimately activated T cells. Additionally, I demonstrated that certain microbes, such as Pseudomonas aeruginosa, which are present in higher numbers in the upper gut of patients with celiac disease, can break down gluten into fragments that further activate T cells. The results validated the use of this model to understand what other co-factors can tip the balance in a person with celiac genes to remain healthy or develop inflammation. In summary, I demonstrated that the gut lining expressing celiac genes actively participates in the activation of immune cells that drive intestinal damage in celiac disease. This new model is a novel tool to continue to identify additional co-factors that predispose patients to celiac disease, as well as to screen for novel therapies for celiac disease. This is important, as the only currently available treatment is a strict lifelong gluten-free diet, which has many limitations, including frequent contamination and celiac disease reactivation.

Name: Life of coeliac and his family in these days Aim: The aim of my diploma thesis is to map life difficulties of people with celiac disease. First of all, it is a problem with gluten-free diet which is essential for celiac disease. Problems with eating out, shopping for ingredients for meal preparation at home, expensiveness of this eating, and last but not least, support from insurance companies and the state. Methods: The theoretical part includes findings about celiac disease as an illness, it means the characteristics of its origin, diagnostics and treatment. Furthermore, findings about gluten- free diet and problems related to this kind of eating were worked. Last but not least, diet and availability of food for gluten-free eating are mentioned. I applied a survey method in the practical part, in which case an anonymous survey was created electronically by using Google forms, and then sent out via internet. The survey was filled out by 296 respondents. Outcome: We can see from the outcomes that most of the respondents sometimes break the diet due to social integration. Furthermore, we observed the frequency of eating in restaurant services, in which case most of the people sometimes visit, it means less than once a week. The reason of sporadic or even no visit to restaurants is bad...

The epithelial cells lining the intestinal mucosa separate the underlying tissue from components of the intestinal lumen. Innate immunity mediated by intestinal epithelial cells (IECs) provides rapid protective functions against microorganisms. Innate immunity also participates in orchestrating adaptive immunity. Key components in innate defence are defensins. To study the production of defensins and how it is affected by intestinal inflammation IECs were isolated from the small and large intestines of patients suffering from ulcerative colitis (UC), Crohn´s disease (MbC), celiac disease (CD), and from controls, and analyzed by quantitative RT-PCR (qRT-PCR) and immunoflow cytometry. Defensin expressing cells were also studied by in situ hybridization and immunohistochemistry. Normally, only small intestinal Paneth cells express human α-defensin 5 (HD-5) and HD-6. In UC colon IECs, HD-5, HD-6, and lysozyme mRNAs were expressed at high levels. In Crohn´s colitis colon the levels of HD-5 and lysozyme mRNAs were also increased although not to the same extent as in UC. No increase was detected in MbC with ileal localization. Metaplastic Paneth cell differentiation in UC colon was primarily responsible for the expression of the antimicrobial components. Human β-defensin 1 (hBD-1) mRNA was more abundant in large than in small intestine of controls, and remained unchanged in UC and MbC. hBD-2 mRNA was barely detectable in normal intestine and was induced in UC IECs but not in MbC IECs. mRNAs for the recently discovered hBD-3 and hBD-4, were detected in IECs from both small and large intestine. Both hBD-3 and hBD-4 mRNA were significantly increased in IECs of UC patients but not of MbC patients. Bacteria and IL-1β induced hBD-2 but not hBD-1 mRNA in colon carcinoma cell lines. IFN-γ, but not TNF-α or IL-1β, augmented hBD-3 expression in these cells, while none of the agents induced hBD-4. High antimicrobial activity of IECs in UC may be a consequence of changes in the epithelial lining, which permit the adherence of microorganisms. Unexpectedly, in situ hybridization revealed expression of hBD-3 and hBD-4 mRNAs by numerous lamina propria cells in colonic tissue from UC patients. These cells were identified as plasma cells (CD138+). hBD-3 and hBD-4 mRNAs were also demonstrated in the plasmacytoma cell line U266. This is the first demonstration of defensins in plasma cells. The four prominent constituents of the intestinal glycocalyx, carcinoembryonic antigen (CEA), CEA cell adhesion molecule 1 (CEACAM1), CEACAM6 and CEACAM7 all seem to play a critical role in innate defence of the intestinal mucosa by trapping and expelling microorganisms at the epithelial surface. The inducibility of these molecules in colonic epithelial cell lines was analyzed by qRT-PCR, immunoflow cytometry, and immunoelectron microscopy. IFN-g but not bacteria, LPS, TNF-α, or IL-1β modified the expression of CEA, CEACAM1 and CEACAM6. None of these agents modified CEACAM7 expression. IFN-γ was shown to have two effects: a direct effect on CEACAM1 transcription, and promotion of cell differentiation resulting in increased CEA and CEACAM6 and decreased CEACAM7 expression. Scanning electron microscopy of jejunal biopsies from children with CD revealed the presence of rod shaped bacteria in ~40% of patients with active CD, but only in 2% of controls. 19% of treated CD patients still had adhering bacteria. Presence of bacteria is not due to lack of antimicrobial factors. In fact, HD-5, HD-6, and lysozyme mRNA levels were significantly increased in IECs of patients with active CD. hBD-1 and hBD-2 were unchanged. Lack of induction of hBD-2 may reflect disturbed signalling in IECs of CD patients. Analysis of CEA and CEACAM1 mRNA/protein expression showed no differences between CD patients and controls. Analysis of the mucins MUC2 and MUC3 revealed significantly increased MUC2 levels in active disease and unchanged MUC3. Immunohistochemistry demonstrated goblet cell metaplasia as well as staining of the apical portion of absorptive cells. Glycosylation status of proteins was studied by lectin histochemistry. Goblet cells in the mucosa of CD patients were stained by the lectin UEAI. This was not seen in controls. The lectin PNA stained the glycocalyx of controls but not that of CD patients. Thus, unique carbohydrate structures of the glycocalyx/mucous layer are likely discriminating features of CD patients and may allow bacterial binding. We conclude that the intestinal epithelium is heavily involved in the innate defence of the mucosa and that its reactive pattern is affected by intestinal inflammation. Keywords: human intestinal mucosa; epithelial cells; innate immunity; defensin; ulcerative colitis; Crohn´s disease; celiac disease; glycoαcalyx; mucin

Most patients with pancreatic cancer will present with metastatic or locally advanced disease. Unfortunately, most patients with localized disease will experience recurrence even after multimodality therapy. As such, pancreatic cancer patients arrive at a common endpoint where decisions pertaining to palliative care come to the forefront. This article summarizes surgical, endoscopic, and other palliative techniques for relief of obstructive jaundice, relief of duodenal or gastric outlet obstruction, and relief of pain due to invasion of the celiac plexus. It also introduces the utility of the palliative care triangle in clarifying a patient's and family's goals to guide decision making.

A doença celíaca (DC) é uma doença inflamatória induzida pela ingestão de glúten em indivíduos geneticamente predispostos e seu tratamento é baseado em uma dieta sem glúten por toda a vida. A doença celíaca refratária é um problema comum que afeta de 10% a 19% dos pacientes célicos tratados. Provavelmente, a contaminação da dieta por glúten é uma das razões principais para a persistência de sintomas em pacientes celíacos tratados, assim como a ingestão inadvertida de glúten, devido a rotulagem incorreta. Assim, o objetivo deste estudo foi avaliar a confiabilidade dos rótulos dos alimentos brasileiros processados, através de testes de contaminação de glúten nos seguintes grupos (a) produtos \"livres de glúten\" - preparados especificamente para a população celíaca; (b) produtos \"naturalmente sem glúten\" feitos com arroz, milho, soja e mandioca, utilizados por toda a população e (c) produtos rotulados com \"contém glúten\", mas que não apresentam glúten em sua composição no rótulo. Foram analisados 213 produtos alimentícios agrupados em: 115 produtos do grupo \"sem glúten\"; 86 produtos do grupo \"naturalmente sem glúten\" e 12 produtos do grupo rotulados com \"contém glúten\". O teor de glúten foi detectado e quantificado por ELISA-R5 (Ridascreen®gliadin) e os resultados foram expressos em ppm e mg/100 g de alimento. A linha de corte foi estabelecida em 20 ppm para a contaminação de glúten. Todas as contaminações por glúten foram confirmadas por Western-blotting. Resultados: (a) alimentos livres de glúten 15 das 115 (13%) apresentaram contaminação por glúten (20 ppm), (b) grupo de alimentos naturalmente sem glúten - 8 de 86 (9,3%) apresentaram contaminação por glúten (20 ppm); (c) grupo de alimentos rotulados com contem glúten - somente 2 de 12 (16,7%) apresentaram contaminação por glúten (20 ppm). A análise de Western-blotting confirmou 36 das 38 (95%) contaminações encontradas no ELISA-R5. CONCLUSÕES: Ambos os grupos de alimentos \"sem glúten\" e \"naturalmente sem glúten\" comercializados no Brasil apresentaram razoável porcentagem de contaminação por glúten, o que dificulta a realização de uma dieta adequada ao paciente celíaco. O grupo de alimentos rotulado \"com glúten\" não apresentou 100% de contaminação, o que revela que a rotulagem desses produtos deve ser feita como uma medida preventiva. Uma maior chance de contaminação pelo glúten foi observada para os produtos a base de arroz (13,6x), soja (13,3x) e milho (9,3x), mas não naqueles à base de mandioca. Em média, encontramos 10,8% (23 de 213) de contaminação de glúten para os alimentos analisados, um panorama positivo para a população brasileira celíaca, principalmente devido ao uso da mandioca, uma alternativa para a farinha de trigo. No entanto, a contaminação de glúten encontrada mostra a importância da quantificação de glúten em todos os alimentos industrializados. / Celiac disease (CD) is an inflammatory disorder induced by ingestion of gluten in genetically predisposed individuals and its treatment is based on a life-time gluten-free diet. Nonresponsive celiac disease is a common problem affecting from 10% to 19% of treated celiac patients. Probably a gluten contamination in diet is one of the major reasons for symptoms persistence in celiac patients as well as an inadvertent gluten intake due to a misleading nutritional label. The aim of this study was to evaluate the reliability of Brazilian processed food labels by testing gluten contamination in (a) gluten-free products - prepared specifically for the celiac population; (b) in naturally gluten-free products made with rice, corn, soy bean and cassava and used by all population and (c) in not gluten-free products labeled to contain gluten but not having it in their composition. We analyzed 213 food samples grouped accordingly to its type: 115 samples of \"gluten-free food, 86 samples of \"naturally gluten-free food and 12 samples of not-gluten free labeled products. The gluten content was detected and quantified by ELISA-R5 (Ridascreen® Gliadin) and the results were expressed in ppm and mg/100 g of food. A cut-off line was established in 20 ppm for gluten contamination. All gluten contaminations were confirmed by Western-blotting. Results: (a) Gluten-free foods - we found 100 of 115 samples (87%) with no contamination (< 20 ppm) and 15 of 115 (13%) showed gluten contamination 20 ppm; (b) Naturally Gluten-free foods - we found 78 of 86 samples (90,7%) showing no contamination (< 20 ppm) and 8 of 86 (9,3%) with gluten levels 20 ppm; (c) Not gluten-free foods - we found 10 of 12 samples (83,3%) showing no contamination (< 20 ppm) and 2 of 12 (16,7%) with gluten contamination 20 ppm. The Western-blotting analysis confirmed 36 of 38 (95%) contaminations found in the ELISA-R5. CONCLUSIONS: Both \"gluten-free and \"naturally gluten-free foods commercialized in Brazil have presented some gluten contamination making a restricted gluten-free diet hard to be achieved by the celiac population. Unexpectedly the not gluten-free group was not entirely contaminated showing a preventive measure in labeling by food companies. A higher odds ratio for gluten contamination was observed for products made with rice (13.6), soy bean (13.3) and corn (9.3) but not to cassava products (not significant). In general, we found a 10.8% (23 of 213) of gluten contamination for all food products analyzed, a positive panorama for the Brazilian celiac population mainly due to cassava products, an alternative for wheat starch. Nevertheless the gluten contamination found here leads us to the importance for a gluten quantification in all industrialized food to guarantee an appropriated diet to the Brazilian celiac group