Diagnosis of Seronegative and Ultrashort Celiac Disease.

In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.

Regional Differences in the Small Intestinal Proteome of Control Mice and of Mice Lacking Lysosomal Acid Lipase.

The metabolic contribution of the small intestine (SI) is still unclear despite recent studies investigating the involvement of single cells in regional differences. Using untargeted proteomics, we identified regional characteristics of the three intestinal tracts of C57BL/6J mice and found that proteins abundant in the mouse ileum correlated with the high ileal expression of the corresponding genes in humans. In the SI of C57BL/6J mice, we also detected an increasing abundance of lysosomal acid lipase (LAL), which is responsible for degrading triacylglycerols and cholesteryl esters within the lysosome. LAL deficiency in patients and mice leads to lipid accumulation, gastrointestinal disturbances, and malabsorption. We previously demonstrated that macrophages massively infiltrated the SI of Lal-deficient (KO) mice, especially in the duodenum. Using untargeted proteomics (ProteomeXchange repository, data identifier PXD048378), we revealed a general inflammatory response and a common lipid-associated macrophage phenotype in all three intestinal segments of Lal KO mice, accompanied by a higher expression of GPNMB and concentrations of circulating sTREM2. However, only duodenal macrophages activated a metabolic switch from lipids to other pathways, which were downregulated in the jejunum and ileum of Lal KO mice. Our results provide new insights into the process of absorption in control mice and possible novel markers of LAL-D and/or systemic inflammation in LAL-D.

Divergent selection for feed efficiency in pigs altered the duodenum transcriptomic response to feed intake and its DNA methylation profiles.

Feed efficiency is a trait of interest in pigs as it contributes to lowering the ecological and economical costs of pig production. A divergent genetic selection experiment from a Large White pig population was performed for 10 generations, leading to pig lines with relatively low- (LRFI) and high- (HRFI) residual feed intake (RFI). Feeding behavior and metabolic differences have been previously reported between the two lines. We hypothesized that part of these differences could be related to differential sensing and absorption of nutrients in the proximal intestine. We investigated the duodenum transcriptome and DNA methylation profiles comparing overnight fasting with ad libitum feeding in LRFI and HRFI pigs (n = 24). We identified 1,106 differentially expressed genes between the two lines, notably affecting pathways of the transmembrane transport activity and related to mitosis or chromosome separation. The LRFI line showed a greater transcriptomic response to feed intake than the HRFI line. Feed intake affected genes from both anabolic and catabolic pathways in the pig duodenum, such as rRNA production and autophagy. Several nutrient transporter and tight junction genes were differentially expressed between lines and/or by short-term feed intake. We also identified 409 differentially methylated regions in the duodenum mucosa between the two lines, while this epigenetic mark was less affected by feeding. Our findings highlighted that the genetic selection for feed efficiency in pigs changed the transcriptome profiles of the duodenum, and notably its response to feed intake, suggesting key roles for this proximal gut segment in mechanisms underlying feed efficiency.NEW & NOTEWORTHY The duodenum is a key organ for the hunger/satiety loop and nutrient sensing. We investigated how the duodenum transcriptome and DNA methylation profiles are affected by feed intakes in pigs. We observed thousands of changes in gene expression levels between overnight-fasted and fed pigs in high-feed efficiency pig lines, but almost none in the related low-feed efficiency pig line.

Altered Genome-Wide DNA Methylation in the Duodenum of Common Variable Immunodeficiency Patients.

PURPOSE: A large proportion of Common variable immunodeficiency (CVID) patients has duodenal inflammation with increased intraepithelial lymphocytes (IEL) of unknown aetiology. The histologic similarities to celiac disease, lead to confusion regarding treatment (gluten-free diet) of these patients. We aimed to elucidate the role of epigenetic DNA methylation in the aetiology of duodenal inflammation in CVID and differentiate it from true celiac disease. METHODS: DNA was isolated from snap-frozen pieces of duodenal biopsies and analysed for differences in genome-wide epigenetic DNA methylation between CVID patients with increased IEL (CVID_IEL; n = 5) without IEL (CVID_N; n = 3), celiac disease (n = 3) and healthy controls (n = 3). RESULTS: The DNA methylation data of 5-methylcytosine in CpG sites separated CVID and celiac diseases from healthy controls. Differential methylation in promoters of genes were identified as potential novel mediators in CVID and celiac disease. There was limited overlap of methylation associated genes between CVID_IEL and Celiac disease. High frequency of differentially methylated CpG sites was detected in over 100 genes nearby transcription start site (TSS) in both CVID_IEL and celiac disease, compared to healthy controls. Differential methylation of genes involved in regulation of TNF/cytokine production were enriched in CVID_IEL, compared to healthy controls. CONCLUSION: This is the first study to reveal a role of epigenetic DNA methylation in the etiology of duodenal inflammation of CVID patients, distinguishing CVID_IEL from celiac disease. We identified potential biomarkers and therapeutic targets within gene promotors and in high-frequency differentially methylated CpG regions proximal to TSS in both CVID_IEL and celiac disease.

AGA Clinical Practice Update on High-Quality Upper Endoscopy: Expert Review.

DESCRIPTION: The purpose of this Clinical Practice Update (CPU) Expert Review is to provide clinicians with guidance on best practices for performing a high-quality upper endoscopic exam. METHODS: The best practice advice statements presented herein were developed from a combination of available evidence from published literature, guidelines, and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out, which aligns with standard processes for American Gastroenterological Association (AGA) Institute CPUs. These statements are meant to provide practical, timely advice to clinicians practicing in the United States. This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates (CPU) Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Clinical Gastroenterology & Hepatology. BEST PRACTICE ADVICE 1: Endoscopists should ensure that upper endoscopy is being performed for an appropriate indication and that informed consent clearly explaining the risks, benefits, alternatives, sedation plan, and potential diagnostic and therapeutic interventions is obtained. These elements should be documented by the endoscopist before the procedure. BEST PRACTICE ADVICE 2: Endoscopists should ensure that adequate visualization of the upper gastrointestinal mucosa, using mucosal cleansing and insufflation as necessary, is achieved and documented. BEST PRACTICE ADVICE 3: A high-definition white-light endoscopy system should be used for upper endoscopy instead of a standard-definition white-light endoscopy system whenever possible. The endoscope used for the procedure should be documented in the procedure note. BEST PRACTICE ADVICE 4: Image enhancement technologies should be used during the upper endoscopic examination to improve the diagnostic yield for preneoplasia and neoplasia. Suspicious areas should be clearly described, photodocumented, and biopsied separately. BEST PRACTICE ADVICE 5: Endoscopists should spend sufficient time carefully inspecting the foregut mucosa in an anterograde and retroflexed view to improve the detection and characterization of abnormalities. BEST PRACTICE ADVICE 6: Endoscopists should document any abnormalities noted on upper endoscopy using established classifications and standard terminology whenever possible. BEST PRACTICE ADVICE 7: Endoscopists should perform biopsies for the evaluation and management of foregut conditions using standardized biopsy protocols. BEST PRACTICE ADVICE 8: Endoscopists should provide patients with management recommendations based on the specific endoscopic findings (eg, peptic ulcer disease, erosive esophagitis), and this should be documented in the medical record. If recommendations are contingent upon histopathology results (eg, H pylori infection, Barrett's esophagus), then endoscopists should document that appropriate guidance will be provided after results are available. BEST PRACTICE ADVICE 9: Endoscopists should document whether subsequent surveillance endoscopy is indicated and, if so, provide appropriate surveillance intervals. If the determination of surveillance is contingent on histopathology results, then endoscopists should document that surveillance intervals will be suggested after results are available.

Video-Based Indocyanine Green Fluorescence Applied to Robotic Duodenum-Preserving Pancreatic Head Resection.

BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) serves as a surgical intervention for managing benign and low-grade malignant neoplasms located in the head of the pancreas. This surgical approach enables the thorough excision of pancreatic head lesions, reducing the necessity for digestive tract reconstruction and enhancing the patient's quality of life.1 Performing a minimally invasive DPPHR is a complex surgical procedure, particularly when safeguarding the bile duct and the pancreaticoduodenal arterial arch. Robotic surgery is among the latest innovations in minimally invasive surgery and is widely used in many surgical specialties. It offers advantages such as rotatable surgical instruments, muscle tremor filters and up to 10-15 times three dimensional (3D) visual field,2 and achieves high flexibility and accuracy in surgical operations. Indocyanine green (ICG) fluorescence imaging technology is also applied to provide real-time intraoperative assessment of the biliary system and blood supply, which helps maintain the biliary system's integrity.3,4 We first report the complete procedure of ICG applied to the da Vinci robotic Xi system for preserving the DPPHR. METHODS: A 48-year-old female patient was diagnosed with pancreatic duct stones, chronic pancreatitis, and pancreatogenic diabetes. Enhanced computed tomography (CT) scans revealed pancreatic head stones, pancreatic atrophy, scattered calcifications, and a dilated pancreatic duct. An attempt at endoscopic retrograde cholangiopancreatography (ERCP) treatment was abandoned during hospitalization due to unsuccessful catheterization. Following informed consent from the patient and her family, a robotic DPPHR was conducted utilizing ICG fluorescence imaging technology. Approximately 60 min before the surgery, 2 mg of ICG was injected via the peripheral vein. The individual was positioned in a reclined posture with the upper part of the bed raised to an angle of 30° and a leftward tilt of 15°. Upon entering the abdominal cavity, existing adhesions were meticulously separated and the gastrocolic ligament was opened to expose the pancreas. The lower part of the pancreas was separated and the superior mesenteric vein (SMV) was identified at the inferior boundary of the pancreatic neck. The pancreas was cut upward and the pancreatic duct was severed using scissors. Dissection of the lateral wall of the portal vein-SMV in the pancreatic head segment was performed. Meticulous dissection was carried out along the pancreatic tissue, retracting the uncinate process of the pancreas in an upward and rightward direction. During the dissection, caution was exercised to protect the anterior and posterior pancreaticoduodenal arterial arch. By using ICG fluorescence imaging, the path of the common bile duct was identified and verified. Caution was exercised to avoid injuring the bile duct. After isolating the CBD, the head and uncinate process of the pancreas was entirely excised. Under the fluorescence imaging mode, the wholeness of the CBD was scrutinized for any potential seepage of the contrast agent. Ultimately, a Roux-en-Y end-to-side pancreaticojejunostomy (duct to mucosa) was executed. RESULTS: The surgery took 265 min and the estimated blood loss was about 150 mL. Without any postoperative complications, the patient was released from the hospital 13 days following the surgery. Postoperative pathology confirmed pancreatic duct stones and chronic pancreatitis. We have successfully performed four cases of robotic DPPHR using this technique, with only one patient experiencing a postoperative complication of pulmonary embolism. All patients were discharged successfully without any further complications. CONCLUSIONS: Employing ICG fluorescence imaging in a robotic DPPHR has been demonstrated to be both secure and achievable. This technique potentially provides novel therapeutic perspectives, particularly for patients with ambiguous delineation between pancreatic and biliary ductal structures.

Long-Term Oncologic Outcome following Duodenum-Preserving Pancreatic Head Resection for Benign Tumors, Cystic Neoplasms, and Neuroendocrine Tumors: Systematic Review and Meta-analysis.

BACKGROUND: Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the potential to cure patients associated with reduced procedure-related short- and long-term complications. MATERIALS AND METHODS: Pubmed, Embase, and Cochrane libraries were searched for studies reporting surgery-related complications following PD and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. A total of 38 cohort studies that included data from 1262 patients were analyzed. In total, 729 patients underwent DPPHR and 533 PD. RESULTS: Concordance between preoperative diagnosis of benign tumors and final histopathology was 90.57% for DPPHR. Cystic and neuroendocrine neoplasms (PNETs) and periampullary tumors (PATs) were observed in 497, 89, and 31 patients, respectively. In total, 34 of 161 (21.1%) patients with intraepithelial papillar mucinous neoplasm exhibited severe dysplasia in the final histopathology. The meta-analysis, when comparing DPPHRt and PD, revealed in-hospital mortality of 1/362 (0.26%) and 8/547 (1.46%) patients, respectively [OR 0.48 (95% CI 0.15-1.58); p = 0.21], and frequency of reoperation of 3.26 % and 6.75%, respectively [OR 0.52 (95% CI 0.28-0.96); p = 0.04]. After a follow-up of 45.8 ± 26.6 months, 14/340 patients with intraductal papillary mucinous neoplasms/mucinous cystic neoplasms (IPMN/MCN, 4.11%) and 2/89 patients with PNET (2.24%) exhibited tumor recurrence. Local recurrence at the resection margin and reoccurrence of tumor growth in the remnant pancreas was comparable after DPPHR or PD [OR 0.94 (95% CI 0.178-5.34); p = 0.96]. CONCLUSIONS: DPPHR for benign, premalignant neoplasms provides a cure for patients with low risk of tumor recurrence and significantly fewer early surgery-related complications compared with PD. DPPHR has the potential to replace PD for benign, premalignant cystic and neuroendocrine neoplasms.

Markedly increased duodenal villous surface apoptosis in patients taking pre-exposure prophylaxis (PrEP) against human immunodeficiency virus.

AIMS: Pre-exposure prophylaxis (PrEP) consists of combination antiretroviral therapy and is increasingly utilized to prevent human immunodeficiency virus (HIV) in high-risk populations. Two index cases noted during routine care showed markedly increased duodenal villous surface apoptosis in patients on PrEP. We sought to examine the prevalence of this finding and identify any clinicopathologic correlations. METHODS: Gastrointestinal biopsy specimens from 23 male patients aged 18-40 years taking PrEP and 23 control patients were reviewed. Patients with HIV, inflammatory gastrointestinal diseases, and celiac disease were excluded. Apoptoses were counted on surface epithelium and deep crypts. The highest apoptotic body count per tissue fragment was recorded. Clusters were defined as groups of ≥5 apoptoses. Apoptotic counts between patients taking PrEP and controls were compared using t-tests. RESULTS: In PrEP patients, the median age was 35 years (range 25-40) and 83% (19/23) were white. The control patients were demographically similar (median age: 32 years [range 23-40]; 70% [16/23] white). Duodenal apoptosis in villous surface epithelium was increased in PrEP patients, with 14/23 (60.9%) patients having ≥10 surface apoptoses compared to 2/23 (8.7%) controls (P = 2.1 × 10-3 ) and 14/23 (61%) having clusters compared to 3/23 (13%) controls (P = 2.0 × 10-3 ). There was no significant association between increased surface apoptosis or clusters and clinical symptoms or duration of PrEP use. CONCLUSION: Markedly increased villous surface apoptosis, particularly in clusters, is often seen in the duodenum of patients taking PrEP. Although the mechanism and significance are unknown, knowledge of this peculiar finding may prevent unnecessary additional testing.

Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

Four cases of non-Helicobacter pylori Helicobacter-infected gastritis with duodenal spiral bacilli.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) is rarely detected in duodenal mucosa due to its preference for slightly acidic environments. Here, we report four cases of NHPH-infected gastritis with duodenal spiral bacilli, potentially NHPH, indicating the possibility of duodenal mucosal infection. CASE PRESENTATION: In every case, gastric mucosa showed endoscopic findings characteristic of NHPH-infected gastritis, and a mucosal biopsy was taken from the duodenal bulb; spiral bacilli were identified under microscopy using Giemsa staining. Case 1, a 46-year-old man, had diffuse spotty redness, mucosal edema, and multiple tiny erosions in the duodenal bulb, along with larger erosions in the second portion of the duodenum upon endoscopic examination. Histopathologically, moderate infiltration of mononuclear cells and neutrophils in the lamina propria and gastric epithelial metaplasia were observed. Case 2, a 54-year-old man, showed an elevated lesion, 1 cm in diameter, with multiple red spots and a few tiny erosions in the duodenal bulb. Histopathologically, mild inflammatory cell infiltration and gastric epithelial metaplasia were observed. In Case 3, a 52-year-old man, endoscopy revealed a flat elevated lesion, 7 mm in diameter, with multiple red spots and a few tiny erosions in the anterior wall of the duodenal bulb. Histopathologically, we observed moderate inflammatory cell infiltration in the gastric antrum and gastric epithelial metaplasia in the duodenal bulb. Case 4, a 40-year-old man, showed mild spotty redness in the duodenal bulb. Histopathologically, mild mononucleocyte infiltration and gastric epithelial metaplasia were observed. A single spiral bacillus was observed in Case 4 by microscopy. In all but Case 2, Helicobacter suis was identified in the gastric juice by polymerase chain reaction analysis. CONCLUSIONS: Spiral bacilli resembling NHPH may infect the duodenal mucosa, particularly the bulb, causing inflammation. Gastric contents entering the duodenum may reduce the intraduodenal pH, promoting NHPH survival and proliferation.

Unanticipated Enhancement of Intestinal TG Output by Apoc3 ASO Inhibition.

BACKGROUND: The objective of this study was to investigate whether apoC3 (apolipoprotein C3) inhibition with an antisense oligonucleotide (ASO) modulates intestinal triglyceride secretion. METHODS: Sprague-Dawley rats were treated with subcutaneous injections of apoC3 ASO 25 mg/kg twice weekly or inactive ASO for 4 weeks before the assessment of lymph flow, triglyceride and apoB48 (apolipoprotein B48) appearance in the lymph. Rats were surgically implanted with catheters in the mesenteric lymph duct and duodenum. Following an overnight fast, an intraduodenal lipid bolus (1.5-mL intralipid) was administered. Lymph fluid was collected for the following 4 hours to compare effects on lymph flow, lymph triglyceride and apoB48 concentration, and secretion. To assess suppression of apoC3 expression and protein abundance by apoC3 ASO compared with inactive ASO (placebo), intestinal and hepatic tissues were collected from a subset of animals before (fasting) and after an enteral lipid bolus (post-lipid). RESULTS: ApoC3 ASO significantly reduced apoC3 mRNA expression in the liver compared with inactive ASO (fasting: 42%, P=0.0048; post-lipid: 66%, P<0.001) and in the duodenum (fasting: 29%, P=0.0424; post-lipid: 53%, P=0.0120). As expected, plasma triglyceride also decreased significantly (fasting: 74%, P<0.001; post-lipid: 33%, P=0.0276). Lymph flow and cumulative lymph volume remained unchanged following apoC3 ASO therapy; however, lymph triglyceride, but not apoB48 output, increased by 38% (ANOVA, P<0.001). Last, no changes were observed in stool triglyceride, intestinal fat (quantified via oil red O staining), and expression of mRNAs involved in triglyceride synthesis, lipid droplet formation, and chylomicron transport and secretion. CONCLUSIONS: Despite the marked reduction in plasma triglyceride concentration that occurs with apoC3 ASO inhibition, intestinal triglyceride output surprisingly increased rather than decreased. These data demonstrate that the reduction of intestinal triglyceride output does not contribute to the potent plasma triglyceride-lowering observed with this novel therapy for hypertriglyceridemia. Further studies are required to explore the mechanism of this intestinal effect.

Endoscopic Diagnosis of Epithelial Subtypes of Superficial Non-Ampullary Duodenal Epithelial Tumors using Magnifying Narrow-Band Imaging.

INTRODUCTION: Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI). METHODS: Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry. RESULTS: Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type. CONCLUSION: Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.

Endoscopic resection for non-ampullary duodenal subepithelial lesions: a retrospective cohort study.

PURPOSE: This study aimed to assess the safety and efficacy of endoscopic submucosal dissection (ESD) and pre-cutting endoscopic mucosal resection (pEMR) in treating non-ampullary duodenal subepithelial lesions (NADSELs) and to evaluate the clinical utility of endoscopic ultrasound (EUS) before endoscopic resection (ER). METHODS: In this retrospective single-centre cohort study, we compared the clinical outcomes of patients with NADSELs who underwent ESD or pEMR between January 2014 and June 2023. The accuracies of EUS in determining the pathological type and origin of the lesions were evaluated using postoperative histopathology as the gold standard. RESULTS: Overall, 56 patients with NADSELs underwent ER in this study, including 16 and 40 treated with pEMR and ESD, respectively. There were no significant differences between the two groups in terms of en bloc resection rate, complete (R0) resection rate, perioperative complication rate, and postoperative hospital length of stay (P > 0.05). However, the pEMR group had significantly shorter median operational (13.0 min vs. 30.5 min, P < 0.001) and mean fasting (1.9 days vs. 2.8 days, P = 0.006) time and lower median hospital costs (¥12,388 vs. ¥19,579, P = 0.002). The accuracies of EUS in determining the pathological type and origin of the lesions were 76.8% and 94.6%, respectively, compared with histopathological evaluation. CONCLUSIONS: EUS can accurately predict the origin of NADSELs. Suitable lesions determined to originate from the submucosa or more superficial layers using EUS can be treated using pEMR as it shortens the operational and recovery time, reduces hospitalisation costs, and achieves an R0 resection rate similar to ESD.

Endoscopic repair of duodenal perforations, a scoping review.

BACKGROUND: There is a discrepancy in the surgical and endoscopic literature for managing duodenal perforations. Although often managed conservatively, surgical repair is the standard treatment for duodenal perforations. This contrasts with the gastroenterology literature, which now recommends endoscopic repair of duodenal perforations, which are more frequently iatrogenic from the growing field of advanced endoscopic procedures. This study aims to provide a scoping review to summarize the current literature content and quality on endoscopic repair of duodenal perforations. METHODS: The protocol for performing this scoping review was outlined by the Joanna Briggs Institute. All studies that reported primary outcomes of patients who had undergone endoscopic repair of duodenal perforations before February 2022, regardless of perforation etiology or repair type were reviewed, with studies after 1999 meeting inclusion criteria. The study excluded articles that did not report clinical outcomes of endoscopic repair, articles that did not describe where in the gastrointestinal tract the endoscopic repair occurred, pediatric patients, and animal studies. RESULTS: 7606 abstracts were screened, with 474 full articles reviewed and 152 studies met inclusion criteria. 560 patients had duodenal perforations repaired endoscopically, with a technical success rate of 90.4% and a survival rate of 86.7%. Most of these perforations (74.5%) were iatrogenic from endoscopic procedures or surgery. Only one randomized control trial (RCT) was found, and 53% of studies were case reports. CONCLUSION: These results suggest that endoscopic repair could emerge as a viable first-line treatment for duodenal perforation and highlight the need for more high-quality research in this topic.

Surgical management of duodenal crohn's disease.

BACKGROUND: Operative options for duodenal Crohn's disease include bypass, stricturoplasty, or resection. What factors are associated with operation selection and whether differences exist in outcomes is unknown. METHODS: Patients with duodenal Crohn's disease requiring operative intervention across a multi-state health system were identified. Patient and operative characteristics, short-term surgical outcomes, and the need for future endoscopic or surgical management of duodenal Crohn's disease were analyzed. RESULTS: 40 patients underwent bypass (n = 26), stricturoplasty (n = 8), or resection (n = 6). Median age of diagnosis of Crohn's disease was 23.5 years, and over half of the patients had undergone prior surgery for CD. Operation type varied by the most proximal extent of duodenal involvement. Patients with proximal duodenal CD underwent bypass operations more commonly than those with mid- or distal duodenal disease (p = 0.03). Patients who underwent duodenal stricturoplasty more often required concomitant operations for other sites of small bowel or colonic CD (63%) compared to those who underwent bypass (39%) or resection (33%). No patients required subsequent surgery for duodenal CD at a median follow-up of 2.8 years, but two patients required endoscopic dilation (n = 1 after stricturoplasty, n = 1 after resection). CONCLUSION: Patients who require surgery for duodenal Crohn's disease appear to have an aggressive Crohn's disease phenotype, represented by a younger age of diagnosis and a high rate of prior resection for Crohn's disease. Choice of operation varied by proximal extent of duodenal Crohn's disease.

2-ethylhexyl diphenyl phosphate exposure induces duodenal inflammatory injury through oxidative stress in chickens.

2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.

Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses.

BACKGROUND: A substantial proportion of common variable immunodeficiency (CVID) patients has duodenal inflammation of largely unknown etiology. However, because of its histologic similarities with celiac disease, gluten sensitivity has been proposed as a potential mechanism. OBJECTIVE: We aimed to elucidate the role of the duodenal microenvironment in the pathogenesis of duodenal inflammation in CVID by investigating the transcriptional, proteomic, and microbial signatures of duodenal biopsy samples in CVID. METHODS: DNA, total RNA, and protein were isolated from snap-frozen pieces of duodenal biopsy samples from CVID (with and without duodenal inflammation), healthy controls, and patients with celiac disease (untreated). RNA sequencing, mass spectrometry-based proteomics, and 16S ribosomal DNA sequencing (bacteria) were then performed. RESULTS: CVID separated from controls in regulation of transcriptional response to lipopolysaccharide and cellular immune responses. These differences were independent of mucosal inflammation. Instead, CVID patients with duodenal inflammation displayed alterations in transcription of genes involved in response to viral infections. Four proteins were differently regulated between CVID patients and healthy controls-DBNL, TRMT11, GCHFR, and IGHA2-independent of duodenal inflammation. Despite similar histology, there were major differences in CVID with duodenal inflammation and celiac disease both at the RNA and protein level. No significant difference was observed in the bacterial gut microbial signature between CVID, celiac, and healthy controls. CONCLUSION: Our findings suggest the existence of altered functions of the duodenal epithelium, particularly in response to lipopolysaccharide and viruses. The latter finding was related to duodenal inflammation, suggesting that viruses, not gluten sensitivity, could be related to duodenal inflammation in CVID.

Computed tomographic diagnosis and clinical outcomes of small intestinal obstruction caused by trichobezoars in client-owned rabbits.

Small intestinal obstruction in rabbits, although demonstrated to be common, is still poorly characterized. The objective of this study was to report features of small intestinal obstruction caused by trichobezoars in rabbits upon CT and their clinical outcomes. Rabbits with a diagnosis of intestinal obstruction that underwent CT scanning were included in this study. From each CT scan, obstruction location, appearance, Hounsfield units, size (mm), volume (mm3), distance from the stomach, and diameter of the small intestine proximal and distal to it, were extracted. Nine rabbits were included in the study. All rabbits presented for anorexia and had a distended or enlarged stomach (7) or abdomen (2). CT scan showed a non-contrast-enhancing, ovoid, smoothly marginated structure with a hyperattenuating rim, heterogeneous center, and variable amount of centrally located gas, in the duodenum (5), the jejunum (2), or the ileum (2). The density of the trichobezoars ranged from -156 to 58 HU (median, -44 HU) and volume ranged from 86.1 to 633.8 mm3 (median, 320.6 mm3). Three rabbits underwent medical management. Two of them survived, and one of them died. Six rabbits underwent surgery, of which three were successfully discharged from the hospital. CT proved to be a valuable imaging modality in rabbits with a suspected intestinal obstruction to provide the exact location of the obstruction and the characteristics of the obstructive material. The location and size of the trichobezoar may have relevant clinical implications.

Expression of chicken epidermal growth factor (cEGF) in Escherichia coli regulates the microflora structure of the duodenum to improve growth performance and intestinal morphogenesis in broilers.

1. A study used gene synthesis to obtain the functional domains of chicken epidermal growth factor (cEGF) and examined their impact on broiler growth performance, small intestinal morphology, digestive enzyme activities in the intestinal contents and the structure of duodenal microflora.2. The pET-32a-cEGF recombinant expression vector was constructed. The specific band at 26 KDa was shown by SDS-PAGE analysis and WB results. The purified protein content was shown to be 1687 µg/ml by assay.3. A total of 180 healthy, one-day-old Arbor Acres male, white-feathered broilers were randomly divided into three dietary treatment groups (six replicate pens, 10 birds per replicate): A control diet (ND); cEGF diet (cEGF), control supplemented with 250 mg/kg cEGF and the control diet (CD) supplemented with 250 mg/kg chlortetracycline.4. The results showed that feeding the cEGF and CD diet reduced FCR of broilers aged 1-21 d, average daily feed intake (ADFI) at 22-42 d, and the FCR in the whole period (1-42 d; p < 0.05). Compared with the ND group, the cEGF diet increased duodenal α-amylase and alkaline phosphatase activities in the 1-21 d, duodenal lipase, alkaline phosphatase, and ileal alkaline phosphatase activities in the post-period and increased villus height in the duodenum and ileum (p < 0.05). In addition, the ACE and Chao1 index for the birds fed cEGF were higher than the ND group (p < 0.05). At the phyla level, Firmicutes and Proteobacteria were dominant in all groups. At the genus level, the dominant genus was Lactobacillus. The LEfSe analysis showed that the cEGF group was enriched by 11 species including Brevibacillus, Eisenbergiella, Cloacibacterium, Butyricoccus spp.5. The addition of 250 mg/kg cEGF to the diet can increase growth performance by improving intestinal development and digestive enzyme activity, which may be related to the duodenal intestinal microflora. Therefore, cEGF is an effective alternative to antibiotics in broiler farming.