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Browsing by Subject "Gastrointestinal tract"

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    Characterisation of Gut Microbiota in Ossabaw and Göttingen Minipigs as Models of Obesity and Metabolic Syndrome
    (Public Library of Science, 2013) Pedersen, Rebecca; Ingerslev, Hans-Christian; Sturek, Michael; Alloosh, Mouhamad; Cirera, Susanna; Christoffersen, Berit Ø.; Moesgaard, Sophia G.; Larsen, Niels; Boye, Mette; Cellular and Integrative Physiology, School of Medicine
    Background: Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs. Methods and findings: The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs' cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine. Conclusion: Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs.
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    Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis
    (Wolters Kluwer, 2024) Shiyanbola, Oyewale; Nigdelioglu, Recep; Dhall, Deepti; González, Iván A.; Warmke, Laura M.; Schechter, Shula; Choi, Won-Tak; Hu, Shaomin; Voltaggio, Lysandra; Zhang, Yujie; Liang, Tom Z.; Ko, Huaibin M.; Charville, Greg W.; Longacre, Teri A.; Pathology and Laboratory Medicine, School of Medicine
    Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2 cm and 18 cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.
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    Highly variable biodistribution of 68Ga labeled somatostatin analogues 68Ga-DOTA-NOC and 68Ga-DOTA-TATE in neuroendocrine tumors: clinical implications for somatostatin receptor directed PET/CT
    (AME, 2022) Cheng, Monica; Tann, Mark; Radiology and Imaging Sciences, School of Medicine
    Background: Somatostatin receptor (SSTR)-targeted positron emission tomography/computed tomography (PET/CT) imaging has risen to the forefront for neuroendocrine tumor (NET) detection and management, yet the variability of significant uptake variability (SUV) as a semiquantitative measure of disease detection and tumor response to treatment has not been fully explored. Methods: We assess the reproducibility and interscan variability of SUV metrics of normal tissue and NET in serial 68Ga-DOTA-NOC and 68Ga-DOTA-TATE PET imaging to clinically monitor disease state. Eighty-one patients were enrolled in this retrospective study. Results: Both primary and metastatic hepatic lesions demonstrated SUV (SUVmean 16.5±8.0). The median SUVmean was 16 for the spleen, 9.7 for the pituitary, 12.6 for the adrenal glands, and 4.8 for the liver. The normal pituitary gland demonstrates focal homogenous uptake with SUVmax range of 4.5-23. The adrenal gland showed uptake with SUVmax range of 4.1-29.4, which is more than two times greater than liver uptake (SUVmean range, 2.3-12.4). Highest physiological uptake seen in the spleen (average SUVmean of 17.3, range of 5.4-34.4). Conclusions: The highly variable nature of regional SUVmean and SUVmax in both physiologic tissue and lesions suggests the need for incorporation of more reliable quantitative measures for clinical decision making.
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    Oh, My Gut! New insights on the role of the gastrointestinal tract and the gut microbiome in chronic kidney disease-mineral and bone disorder
    (Wolters Kluwer, 2024) Mirmohammadali, Seyedeh Nooshan; Hill Gallant, Kathleen M.; Biruete, Annabel; Medicine, School of Medicine
    Purpose of review: The aim of this review is to highlight recent evidence on the role of the gastrointestinal tract and gut microbiome on chronic kidney disease-mineral bone disorder (CKD-MBD) outcomes, including intestinal phosphorus absorption and sensing, and the effect of gut-oriented therapies. Recent findings: Recent evidence has revealed a complex interplay among mineral metabolism and novel gut-related factors, including paracellular intestinal phosphate absorption, the gut microbiome, and the immune system, prompting a reevaluation of treatment approaches for CKD-MBD. The inhibition of NHE3 limits phosphate transport in the intestine and may lead to changes in the gut microbiome. A study in rats with CKD showed that the supplementation of the fermentable dietary inulin delayed CKD-MBD, lowering circulating phosphorus and parathyroid hormone, reducing bone remodeling and improving cortical parameters, and lowering cardiovascular calcifications. In non-CKD preclinical studies, probiotics and prebiotics improved bone formation mediated through the effect of butyrate facilitating the differentiation of T cells into Tregs, and Tregs stimulating the osteogenic Wnt10b, and butyrate was also necessary for the parathyroid hormone (PTH) bone effects. Summary: Recent findings support multiple possible roles for gut-oriented therapies in addressing CKD-MBD prevention and management that should be further explored through clinical and translational studies.
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    Phosphate Binders and Non-Phosphate Effects in the Gastrointestinal Tract
    (Elsevier, 2020-01) Biruete, Annabel; Hill Gallant, Kathleen M.; Lindemann, Stephen R.; Wiese, Gretchen; Chen, Neal; Moe, Sharon; Medicine, School of Medicine
    Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.
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    Reimagining Gastroenterology Fellowship Training – The Third Year of the Future
    (Elsevier, 2023) Bhavsar-Burke, Indira; Shah, Brijen J.; Carethers, John M.; Whitson, Matthew J.; Kaul, Vivek; David, Yakira; Dilly, Christen K.; Medicine, School of Medicine
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    The Clinical Significance of Incidental GIT Uptake on PET/CT: Radiologic, Endoscopic, and Pathologic Correlation
    (MDPI, 2023-03-30) Hosni, Mohammad N.; Kassas, Mutaz; Itani, Mohamad I.; Rahal, Mahmoud A.; Al-Zakleet, Safaa; El-Jebai, Malak; Abi-Ghanem, Alain S.; Moukaddam, Hicham; Haidar, Mohamad; Vinjamuri, Sobhan; Shaib, Yasser H.; Medicine, School of Medicine
    Incidental gastrointestinal tract (GIT) [18F]-Fluorodeoxyglucose (FDG) uptake in positron emission technology/computed tomography (PET/CT) is an unexpected and often complicated finding for clinicians. This retrospective study reviewed 8991 charts of patients who underwent PET/CT: 440 patients had incidental GIT uptake, of which 80 underwent endoscopy. Patient characteristics, imaging parameters, and endoscopic findings were studied. Of the 80 patients, 31 had cancer/pre-cancer lesions (16 carcinomas; 15 pre-malignant polyps). Compared to patients with benign/absent lesions, patients with cancer/pre-cancer lesions were significantly older (p = 0.01), underwent PET/CT for primary evaluation/staging of cancer (p = 0.03), had focal GIT uptake (p = 0.04), and had lower GIT uptake (p = 0.004). Among patients with focal uptake, an SUVmax of 9.2 had the highest sensitivity (0.76) and specificity (0.885) in detecting cancer/pre-cancerous lesions. Lower GIT uptake was most common in the sigmoid colon, and upper GIT uptake was most frequent in the stomach. In a bivariate analysis, predictors of cancer/pre-cancer were older age, PET/CT indicated for primary evaluation, focal uptake, uptake in the lower GIT, and higher SUVmax. Further endoscopic investigation is warranted for patients with incidental GIT uptake, especially in the elderly or those presenting for primary evaluation with PET/CT, with the following findings on imaging: lower GIT uptake, focal uptake, or high SUVmax.
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    What is the Clinical Impact of a Multiplex Gastrointestinal Panel in Children?
    (Oxford University Press, 2022) Liepmann, Claire; Hecht, Shaina; Pediatrics, School of Medicine
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