Toll-like receptors 1-9 in small bowel neuroendocrine tumors-Clinical significance and prognosis.

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1-9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1-2 and 4-9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1-9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07-14.3). The expression of TLRs 1-6 and 8-9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1-2 and 4-9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors.

Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examination.

BACKGROUND: Magnetically assisted capsule endoscopy (MACE) showed the feasibility for upper gastrointestinal examination. To further enhance the performance of conventional MACE, it is necessary to provide quality-improved and three-dimensional images. The aim of this clinical study was to determine the efficacy and safety of novel three-dimensional MACE (3D MACE) for upper gastrointestinal and small bowel examination at once. METHODS: This was a prospective, single-center, non-randomized, and sequential examination study (KCT0007114) at Dongguk University Ilsan Hospital. Adult patients who visited for upper endoscopy were included. The study protocol was conducted in two stages. First, upper gastrointestinal examination was performed using 3D MACE, and a continuous small bowel examination was performed by conventional method of capsule endoscopy. Two hours later, an upper endoscopy was performed for comparison with 3D MACE examination. The primary outcome was confirmation of major gastric structures (esophagogastric junction, cardia/fundus, body, angle, antrum, and pylorus). Secondary outcomes were confirmation of esophagus and duodenal bulb, accuracy for gastric lesions, completion of small bowel examination, 3D image reconstruction of gastric lesion, and safety. RESULTS: Fifty-five patients were finally enrolled. The examination time of 3D MACE was 14.84 ± 3.02 minutes and upper endoscopy was 5.22 ± 2.39 minutes. The confirmation rate of the six major gastric structures was 98.6% in 3D MACE and 100% in upper endoscopy. Gastric lesions were identified in 43 patients during 3D MACE, and 40 patients during upper endoscopy (Sensitivity 0.97). 3D reconstructed images were acquired for all lesions inspected by 3D MACE. The continuous small bowel examination by 3D MACE was completed in 94.5%. 3D MACE showed better overall satisfaction (3D MACE 9.55 ± 0.79 and upper endoscopy 7.75 ± 2.34, p<0.0001). There were no aspiration or significant adverse event or capsule retention in the 3D MACE examination. CONCLUSIONS: Novel 3D MACE system is more advanced diagnostic modality than the conventional MACE. And it is possible to perform serial upper gastrointestinal and small bowel examination as a non-invasive and one-step test. It would be also served as a bridge to pan-endoscopy.

Jejunal Diverticulosis Causing Small Intestinal Volvulus and Closed Loop Obstruction.

BACKGROUND Jejunal diverticulosis are false diverticula of the small bowel that form from outpouching of the mucosa and submucosa. They are pulsion diverticula that are often asymptomatic and can be found incidentally during surgery. In some instances, jejunal diverticula could result in intestinal obstruction. Small intestinal volvulus is an uncommon cause of small bowel obstruction that results in a closed loop obstruction and is an indication for emergent surgical intervention. CASE REPORT We report a case of an 84-year-old man who presented to the Emergency Department with abdominal pain and generalized weakness. A preoperative computerized tomographic scan demonstrated a closed loop small bowel obstruction with mesenteric swirling. The patient was taken for a diagnostic laparoscopy, which revealed extensive proximal jejunal diverticulosis and a volvulus of the involved jejunum. An exploratory laparotomy was warranted for safe detorsion of the small bowel and resection of the diseased segment. The small bowel was successfully detorsed, with resection of the involved jejunum. Intestinal continuity was established by a primary side-to-side anastomosis. CONCLUSIONS Jejunal diverticula have been reported in the literature as a cause of small bowel obstructions, and very few reports exist of concurrent small bowel volvulus. In very rare instances, both of these conditions can coexist. There should be prompt surgical intervention in all cases of closed loop small bowel obstructions to prevent intestinal ischemia, perforation, and sepsis.

Studying the cellular basis of small bowel enteropathy using high-parameter flow cytometry in mouse models of primary antibody deficiency.

Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined. Methods: In this study, several mouse strains reflecting a spectrum of primary antibody deficiency (IgA-/-, Aicda-/-, CD19-/- and JH -/-) were used to generate a functional small-bowel-specific cellular atlas using a novel high-parameter flow cytometry approach that allows for the enumeration of 59 unique cell subsets. Using this cellular atlas, we generated a direct and quantifiable estimate of immune dysregulation. This estimate was then used to identify specific immune factors most predictive of the severity of inflammatory disease of the small bowel (small bowel enteropathy). Results: Results from our experiments indicate that the severity of primary antibody deficiency positively correlates with the degree of immune dysregulation that can be expected to develop in an individual. In the SI of mice, immune dysregulation is primarily explained by defective homeostatic responses in T cell and invariant natural killer-like T (iNKT) cell subsets. These defects are strongly correlated with abnormalities in the balance between protein (MHCII-mediated) versus lipid (CD1d-mediated) antigen presentation by intestinal epithelial cells (IECs) and intestinal stem cells (ISCs), respectively. Conclusions: Multivariate statistical approaches can be used to obtain quantifiable estimates of immune dysregulation based on high-parameter flow cytometry readouts of immune function. Using one such estimate, we reveal a previously unrecognized tradeoff between iNKT cell activation and type 1 immunity that underlies disease in the small bowel. The balance between protein/lipid antigen presentation by ISCs may play a crucial role in regulating this balance and thereby suppressing inflammatory disease in the small bowel.

Isolation of Myenteric and Submucosal Plexus from Mouse Gastrointestinal Tract and Subsequent Co-Culture with Small Intestinal Organoids.

Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle cells, the immune system, and the microbiota. The disruption of this balance underpins the onset of gastrointestinal-related diseases. The scarcity of models replicating the intricate interplay between the ENS and the intestinal epithelium highlights the imperative for developing novel methods. We have pioneered a sophisticated tridimensional in vitro technique, coculturing small intestinal organoids with myenteric and submucosal neurons. Notably, we have made significant advances in (1) refining the isolation technique for culturing the myenteric plexus, (2) enhancing the isolation of the submucosal plexus-both yielding mixed cultures of enteric neurons and glial cells from both plexuses, and (3) subsequently co-culturing myenteric and submucosal neurons with small intestinal organoids. This co-culture system establishes neural innervations with intestinal organoids, allowing for the investigation of regulatory interactions in the context of gastrointestinal diseases. Furthermore, we have developed a method for microinjecting the luminal space of small intestinal organoids with fluorescently labeled compounds. This technique possesses broad applicability such as the assessment of intestinal permeability, transcytosis, and immunocytochemical and immunofluorescence applications. This microinjection method could be extended to alternative experimental setups, incorporating bacterial species, or applying treatments to study ENS-small intestinal epithelium interactions. Therefore, this technique serves as a valuable tool for evaluating the intricate interplay between neuronal and intestinal epithelial cells (IECs) and shows great potential for drug screening, gene editing, the development of novel therapies, the modeling of infectious diseases, and significant advances in regenerative medicine. The co-culture establishment process spans twelve days, making it a powerful asset for comprehensive research in this critical field.

Infant milk formula, produced by membrane filtration, promotes mucus production in the upper small intestine of young pigs.

Human breast milk promotes maturation of the infant gastrointestinal barrier, including the promotion of mucus production. In the quest to produce next generation infant milk formula (IMF), we have produced IMF by membrane filtration (MEM-IMF). With a higher quantity of native whey protein, MEM-IMF more closely mimics human breast milk than IMF produced using conventional heat treatment (HT-IMF). After a 4-week dietary intervention in young pigs, animals fed a MEM-IMF diet had a higher number of goblet cells, acidic mucus and mucin-2 in the jejunum compared to pigs fed HT-IMF (P < 0.05). In the duodenum, MEM-IMF fed pigs had increased trypsin activity in the gut lumen, increased mRNA transcript levels of claudin 1 in the mucosal scrapings and increased lactase activity in brush border membrane vesicles than those pigs fed HT-IMF (P < 0.05). In conclusion, MEM-IMF is superior to HT-IMF in the promotion of mucus production in the young gut.

The bile salt/phospholipid ratio determines the extent of in vitro intestinal lipolysis of triglycerides: Interfacial and emulsion studies.

This study focused on the protein-stabilised triglyceride (TG)/water interfaces and oil-in-water emulsions, and explored the influence of varying molar ratios of bile salts (BSs) and phospholipids (PLs) on the intestinal lipolysis of TGs. The presence of these two major groups of biosurfactants delivered with human bile to the physiological environment of intestinal digestion was replicated in our experiments by using mixtures of individual BSs and PLs under in vitro small intestinal lipolysis conditions. Conducted initially, retrospective analysis of available scientific literature revealed that an average molar ratio of 9:4 for BSs to PLs (BS/PL) can be considered physiological in the postprandial adult human small intestine. Our experimental data showed that combining BSs and PLs synergistically enhanced interfacial activity, substantially reducing oil-water interfacial tension (IFT) during interfacial lipolysis experiments with pancreatic lipase, especially at the BS/PL-9:4 ratio. Other BS/PL molar proportions (BS/PL-6.5:6.5 and BS/PL-4:9) and an equimolar amount of BSs (BS-13) followed in IFT reduction efficiency, while using PLs alone as biosurfactants was the least efficient. In the following emulsion lipolysis experiments, BS/PL-9:4 outperformed other BS/PL mixtures in terms of enhancing the TG digestion extent. The degree of TG conversion and the desorption efficiency of interfacial material post-lipolysis correlated directly with the BS/PL ratio, decreasing as the PL proportion increased. In conclusion, this study highlights the crucial role of biliary PLs, alongside BSs, in replicating the physiological function of bile in intestinal lipolysis of emulsified TGs. Our results showed different contributions of PLs and BSs to lipolysis, strongly suggesting that any future in vitro studies aiming to simulate the human digestion conditions should take into account the impact of biliary PLs - not just BSs - to accurately mimic the physiological role of bile in intestinal lipolysis. This is particularly crucial given the fact that existing in vitro digestion protocols typically focus solely on applying specific concentrations and/or compositions of BSs to simulate the action of human bile during intestinal digestion, while overlooking the presence and concentration of biliary PLs under physiological gut conditions.

CLINICAL AND SURGICAL DILEMMAS IN OCTOGENARIAN PATIENTS WITH SMALL BOWEL OBSTRUCTION.

BACKGROUND: Small bowel obstruction (SBO) is a major problem in emergencies. Comorbidities increase morbimortality, which is reflected in higher costs. There is a lack of Latin American evidence comparing the differences in postoperative results and costs associated with SBO management. AIMS: To compare the risk of surgical morbimortality and costs of SBO surgery treatment in patients older and younger than 80 years. METHODS: Retrospective analysis of patients diagnosed with SBO at the University of Chile Clinic Hospital from January 2014 to December 2017. Patients with any medical treatment were excluded. Parametric statistics were used (a 5% error was considered statistically significant, with a 95% confidence interval). RESULTS: A total of 218 patients were included, of which 18.8% aged 80 years and older. There were no differences in comorbidities between octogenarians and non-octogenarians. The most frequent etiologies were adhesions, hernias, and tumors. In octogenarian patients, there were significantly more complications (46.3 vs. 24.3%, p=0.007, p<0.050). There were no statistically significant differences in terms of surgical complications: 9.6% in <80 years and 14.6% in octogenarians (p=0.390, p>0.050). In medical complications, a statistically significant difference was evidenced with 22.5% in <80 years vs 39.0% in octogenarians (p=0.040, p<0.050). There were 20 reoperated patients: 30% octogenarians and 70% non-octogenarians without statistically significant differences (p=0.220, p>0.050). Regarding hospital stay, the average was significantly higher in octogenarians (17.4 vs. 11.0 days; p=0.005, p<0.050), and so were the costs, being USD 9,555 vs. USD 4,214 (p=0.013, p<0.050). CONCLUSIONS: Patients aged 80 years and older with surgical SBO treatment have a higher risk of medical complications, length of hospital stay, and associated costs compared to those younger.

Chylomicron retention disease: a rare aetiology of failure to thrive.

The aetiology of failure to thrive (FTT) in children is broad, of which some conditions are extremely rare. It is important to consider these rarer conditions, especially in the setting of other concerning signs/symptoms or when there is no improvement with conventional treatment. In this case report we highlight such a rare condition-chylomicron retention disease (CRD) as an aetiology of FTT. CRD often presents with non-specific symptoms, resulting in delayed diagnosis which is established by genetic workup and histology from small intestinal biopsies. Despite being rare, CRD needs to be considered as one of the differential diagnoses after ruling out the more common causes of FTT.

Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review.

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.

Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. METHODS AND RESULTS: Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. CONCLUSIONS: OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

A non-invasive tool to collect small intestine content in post weaning pigs: validation study.

The Capsule for Sampling (CapSa) is an ingestible capsule that collects small intestine content while transiting through the natural digestive pathway. In this study, 14 Swiss Large White pigs weighing less than 12 kg (Category < 12 kg) and 12 weighing between 12 and 20 kg (Category [12-20 kg]) were given two CapSas and monitored for three days. The animals were euthanized for post-mortem sampling, allowing us to directly obtain gut microbiota samples from the gastrointestinal tract. This post-mortem approach enabled a direct comparison between the microbial content from the gut and the samples collected via the CapSas, and it also facilitated precise identification of the CapSas' sampling sites within the gastrointestinal tract. For the category under 12 kg, only 2.3% of the administered CapSas were recovered from the feces. In contrast, in the 12-20 kg category, 62.5% of the CapSas were successfully retrieved from the feces within 48 h. Of these recovered CapSas, 73.3%-equating to 11 capsules from eight pigs-had a pH > 5.5 and were therefore selected for microbiome analysis. Bacterial composition of the CapSas was compared with that of the three segments of the small intestine, the large intestine and feces of the corresponding pig. The results were tested using a PERMANOVA model (Adonis) including sample type as a factor, and then pairwise comparisons were made. The bacterial composition found in the CapSas differed from that of the large intestine and feces (P < 0.01), while it did not differ from the first segment of the small intestine (P > 0.10). This study provides evidence that the CapSa effectively samples the intestinal microbiota from the upper section of the small intestine in post-weaning pigs. Furthermore, it was found that the collection of CapSas could only be successfully achieved in pigs classified within the heavier weight category.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

Double balloon enteroscopy versus single balloon enteroscopy: A comparative study.

Device assisted enteroscopy (DAE) like the double balloon enteroscopy (DBE) and single balloon enteroscopy (SBE) are postulated to ease small bowel examination and performance of therapy. However, studies comparing the effectiveness of these 2 modalities have yielded varying results. The aim of this study is to compare the efficacy and safety of SBE and DBE. We retrospectively reviewed records of patients who underwent DBE (n = 82) or SBE (n = 45) for small bowel exam in our unit from January 2014 to January 2022. Our primary outcomes were to compare the technical success and diagnostic success rates between DBE and SBE. Our secondary outcomes were to compare the therapeutic success, and complication rates. The main indications were suspected GI bleeding (DBE 41.5% vs SBE 48.9%), iron deficiency anemia (DBE 9.8% vs SBE 4.4%) and small bowel lesions (DBE 28.0% vs SBE 44.4%) detected either from prior capsule endoscopy or radiological imaging. Majority of the enteroscopy exam was by antegrade approach (DBE 67.1% vs SBE 77.8%). We found no significant difference in the technical success (DBE 95.1% vs SBE 97.8%, P = .46), diagnostic success (DBE 69.5% vs SBE 77.8%, P = .36) and the therapeutic success rate (DBE 63.2% vs SBE 54.3%, P = .09) between the groups. Complications occurred in 1 case from each group (mucosal tear). None of the complications were major. In patients who underwent enteroscopy, the diagnostic and therapeutic performance of SBE is similar to DBE. Both procedures were safe with low complication rates.

Artificial intelligence in detection of small bowel lesions and their bleeding risk: A new step forward.

The present letter to the editor is related to the study with the title "Automatic detection of small bowel (SB) lesions with different bleeding risk based on deep learning models". Capsule endoscopy (CE) is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate. The development of artificial intelligence (AI) in CE could simplify physicians' tasks. The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk, and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

Reinforcing decellularized small intestine submucosa with cellulose acetate nanofibrous and silver nanoparticles as a scaffold for wound healing applications.

BACKGROUND: The formation of chronic wounds accounts for considerable costs in health care systems. Despite the several benefits of decellularized small intestinal submucosa (SIS) as an appropriate scaffold for different tissue regeneration, it has shortcomings such as lack of antibacterial features and inappropriate mechanical properties for skin tissue regeneration. We aimed to examine the efficacy and safety of decellularized SIS scaffold enhanced with cellulose acetate (CA) and silver (Ag) nanoparticles (NPs) for healing full-thickness wounds. METHODS AND RESULTS: The scaffolds were prepared by decellularizing bovine SIS and electrospinning CA/Ag nanoparticles and characterized using a transmission electron microscope (TEM), scanning electron microscope (SEM), tensile testing, and X-ray diffraction. In vivo evaluations were performed using full-thickness excisions covered with sterile gauze as the control group, SIS, SIS/CA, and SIS/CA/Ag scaffolds on the dorsum of twenty male Wistar rats divided into four groups randomly with 21-days follow-up. All in vivo specimens underwent Masson's trichrome (MT) staining for evaluation of collagen deposition, transforming growth factor-ß (TGF-ß) immunohistochemistry (IHC), and Haematoxylin Eosin (H&E) staining. The IHC and MT data were analyzed with the ImageJ tool by measuring the stained area. The TEM results revealed that Ag nanoparticles are successfully incorporated into CA nanofibers. Assessment of scaffolds hydrophilicity demonstrated that the contact angle of SIS/CA/Ag scaffold was the lowest. The in vivo results indicated that the SIS/CA/Ag scaffold had the most significant wound closure. H&E staining of the in vivo specimens showed the formation of epidermal layers in the SIS/CA/Ag group on day 21. The percentage of the stained area of MT and TGF-ß IHC staining's was highest in the SIS/CA/Ag group. CONCLUSION: The decellularized SIS/CA/Ag scaffolds provided the most significant wound closure compared to other groups and caused the formation of epidermal layers and skin appendages. Additionally, the collagen deposition and expression of TGF-ß increased significantly in SIS/CA/Ag group.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile / Características clínicas y pronóstico de los tumores malignos de intestino delgado: experiencia en un hospital universitario de Chile

Background Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America.AimTo describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs.MethodsRetrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile.ResultsA total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1–99.2), 82.2% (95%CI: 57.6–93.3), 40.0% (95%CI: 16.5–82.8) and 25.9% (95%CI: 4.5–55.7%), respectively. NET (HR 6.1; 95%CI: 2.1–17.2) and GIST (HR 24.4; 95%CI: 3.0–19.8) were independently associated with higher survival compared to AC, adjusted for age and sex.ConclusionsMalignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes. (AU)

Introducción Los tumores del intestino delgado (TID) son infrecuentes y la información sobre ellos es escasa en Latinoamérica.ObjetivoDescribir la epidemiología, características clínicas, métodos diagnósticos y supervivencia de los TID malignos.MétodosEstudio observacional retrospectivo de pacientes adultos con diagnóstico histopatológico de TID entre 2007-2021 en un hospital universitario de Chile.ResultadosSe observaron 104 pacientes (51,9% hombres; edad media 57 años) con TID. El tipo histológico fue tumor neuroendocrino (TNE) (43,7%, n=38), tumor estromal gastrointestinal (GIST) (21,8%, n=19), linfoma (17,2%, n=15) y adenocarcinoma (AC) (11,5%, n=10). Los GIST fueron más frecuentes en el duodeno (50%; n=12) y los TNE en el íleon (65,8%; n=25). Hubo 17 casos de metástasis, más comúnmente de colon y melanoma. Las náuseas y los vómitos se observaron con mayor frecuencia en AC (p=0,035), así como el sangrado gastrointestinal en GIST (p=0,007). Las herramientas de valoración más comunes fueron TC y enteroclisis por TC con un rendimiento diagnóstico alto (86% y 94%, respectivamente). La supervivencia a cinco años de los GIST, TNE, linfoma y AC fue 94,7% (intervalo de confianza [IC] 95%: 68,1-99,2), 82,2% (IC 95%: 57,6-93,3), 40,0% (IC 95%: 16,5-82,8) y 25,9% (IC 95%: 4,5-55,7), respectivamente. Los TNE (hazard ratio [HR] 6,1; IC 95%: 2,1-17,2) y GIST (HR 24,4; IC 95%: 3,0-19,8) se asociaron de forma independiente con una mayor supervivencia en comparación con AC, ajustado por edad y sexo.ConclusionesLos TID malignos son enfermedades poco frecuentes y los TNE son el subtipo histológico más común. La presentación clínica en el momento del diagnóstico, localización o complicaciones pueden sugerir un dictamen más probable. Los GIST y TNE se asocian a una mejor supervivencia en comparación con otros subtipos malignos. (AU)

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model.

Postnatal development of the gastrointestinal tract involves the establishment of the commensal microbiota, the acquisition of immune tolerance via a balanced immune cell composition, and maturation of the intestinal epithelium. While studies have uncovered an interplay between the first two, less is known about the role of the maturing epithelium. Here we show that intestinal-epithelial intrinsic expression of lysine-specific demethylase 1A (LSD1) is necessary for the postnatal maturation of intestinal epithelium and maintenance of this developed state during adulthood. Using microbiota-depleted mice, we find plasma cells, innate lymphoid cells (ILCs), and a specific myeloid population to depend on LSD1-controlled epithelial maturation. We propose that LSD1 controls the expression of epithelial-derived chemokines, such as Cxcl16, and that this is a mode of action for this epithelial-immune cell interplay in local ILC2s but not ILC3s. Together, our findings suggest that the maturing epithelium plays a dominant role in regulating the local immune cell composition, thereby contributing to gut homeostasis.