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Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital., Methods: The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985 , CYP2C9*3 rs1057910 , CYP2C8*3 rs11572080 , CYP2C8*3 rs10509681 , PTGS-1 rs10306135 , PTGS-1 rs12353214 , and PTGS-2 rs20417 using real-time PCR., Results: In NSAIDs + patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30-22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15-8.46), and alcohol intake (OR=4.09, 95 % CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs + patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions., Conclusions: Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13 C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening., (© 2024 UICC.)

Background and Aims: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract., Methods: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification., Results: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB., Conclusions: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events., Competing Interests: Disclosure M. Bruno: Consultant for and support for industry and investigator-initiated studies from Boston Scientific, Cook Medical, and Pentax Medical; support for investigator-initiated studies from Mylan, AMBU, and ChiRoStim. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians', students', and patients' assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients' HRQoL. Correlation was assessed through Pearson's and Kendall's τb coefficients. Physicians' and patients' assessments correlated for one out of six of the functional and a third of the symptom scores. Students' and patients' assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients' symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients' symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL., (© 2024. The Author(s).)

Aims: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy., Methods and Results: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies., Conclusions: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Objective: This article aimed to analyze upper endoscopic findings in the HIV patient population to elucidate the upper-gastrointestinal complications related to HIV infection. Gastrointestinal (GI) disorders in individuals living with HIV/AIDS exhibit diverse and often nonspecific manifestations, imposing substantial morbidity and mortality burdens. Endoscopic evaluation with biopsies is essential in the diagnosis and management of these conditions. Delayed treatment due to undetected GI abnormalities during endoscopic examinations can lead to poorer health outcomes., Methods: This systematic review has determined the findings of upper-GI endoscopy of HIV-infected patients. Online databases of PubMed, Web of Science, Jisc Library Hub Discover, and Library of Congress have been searched using relevant keyword combinations. We have retrieved all the pertinent papers and reports published in English and screened them against inclusion/exclusion criteria for data extraction in two steps. First, titles/abstracts have been evaluated and then full-text screening has been performed by independent researchers. This study has adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist., Results: In this review, 24 articles have been included in the final analysis. The study has focused on the characteristics of participants and the findings of endoscopic evaluations. The participants of the study have been HIV-positive patients, and the majority of them have undergone endoscopy due to gastrointestinal symptoms. The biopsy regions primarily targeted have been observed to be the esophagus, stomach, and duodenum. The most common result of the biopsy specimens has been chronic active gastritis., Conclusion: To improve clinical practice, this systematic review sought to provide an up-to-date reference for upper gastrointestinal endoscopic findings of HIV-infected persons. Our results are in line with earlier research showing how effective endoscopy is for determining a precise diagnosis and directing care. The majority of HIV patients with gastrointestinal symptoms have been found to have opportunistic infections and persistent active gastritis as well as mucosal abnormalities of the upper gastrointestinal tract. Studies have shown that endoscopic and histological assessment can aid in the early detection and management of issues involving the upper gastrointestinal tract., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There is limited evidence on the comparative diagnostic performance of endoscopic tissue sampling techniques for subepithelial lesions. We performed a systematic review with network meta-analysis to compare these techniques., Methods: A systematic literature review was conducted for randomized controlled trials (RCTs) comparing the sample adequacy and diagnostic accuracy of bite-on-bite biopsy, mucosal incision-assisted biopsy (MIAB), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and EUS-guided fine-needle biopsy (FNB). Results were expressed as relative risk (RR) and 95%CI., Results: Eight RCTs were identified. EUS-FNB was significantly superior to EUS-FNA in terms of sample adequacy (RR 1.20 [95%CI 1.05-1.45]), whereas none of the other techniques significantly outperformed EUS-FNA. Additionally, bite-on-bite biopsy was significantly inferior to EUS-FNB (RR 0.55 [95%CI 0.33-0.98]). Overall, EUS-FNB appeared to be the best technique (surface under cumulative ranking [SUCRA] score 0.90) followed by MIAB (SUCRA 0.83), whereas bite-on-bite biopsy showed the poorest performance. When considering lesions <20 mm, MIAB, but not EUS-FNB, showed significantly higher accuracy rates compared with EUS-FNA (RR 1.68 [95%CI 1.02-2.88]). Overall, MIAB ranked as the best intervention for lesions <20 mm (SUCRA score 0.86 for adequacy and 0.91 for accuracy), with EUS-FNB only slightly superior to EUS-FNA. When rapid on-site cytological evaluation (ROSE) was available, no difference between EUS-FNB, EUS-FNA, and MIAB was observed., Conclusion: EUS-FNB and MIAB appeared to provide better performance, whereas bite-on-bite sampling was significantly inferior to the other techniques. MIAB seemed to be the best option for smaller lesions, whereas EUS-FNA remained competitive when ROSE was available., Competing Interests: S.F. Crinò is a consultant for Steris Endsocopy. A. Fugazza is a consultant for Boston Scientific. S. Carrara is a consultant for Olympus. B. Mangiavillano is a consultant for Taewoong Medical. A. Repici is a consultant for Boston Scientific and Medtronic, and has received grant support from Fujifilm. A. Facciorusso, M. Spadaccini, M. Colombo, D. Ramai, S. Chandan, P. Gkolfakis, B.P. Mohan, and C. Hassan declare that they have no conflict of interest., (Thieme. All rights reserved.)

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system., (© 2023. The Author(s).)

Background. The recent studies indicate that one of the causes of allergic dermatoses (AD) in children and adults is pathology of the gastrointestinal tract. However, many problems of the emergence of these combinations have not yet been resolved. The purpose of the study was to establish the incidence and the nature of lesions of the upper gastrointestinal tract (UGIT) in children with allergic dermatoses. Materials and methods. On the base of the Chernivtsi Regional Children’s Hospital, 40 children with allergic dermatoses combined with the pathology of the upper gastrointestinal tract and 20 patients with AD, but without the UGIT pathology, aged 3 to 18 years were examined. A clinical and laboratory studies were conducted twice (routine clinical tests, chamber scratch test with non-infectious allergens during AD remission), as well as fibrogastroduodenoscopy, ultrasound, pH-measuring biochemical blood tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutaminetransferase (GGTP), alkaline phosphatase, cholesterol), identification of H.pylori. Results. It was indicated that out of 40 examined children with AD, 30 (75 %) persons had various lesions of the esophagus, stomach and duodenum. In 10 (25 %) children, the functional changes, such as duodenogastral reflex (70 %) and failure of the cardia (30 %), were detected. A multiple nature of reflux was observed in 85.7 % of children with chronic gastroduodenitis and in 100 % of children with esophagitis and duodenal ulcer disease. The contamination with H.pylori was detected in 72.5 % of cases. The increased activity of ALT and AST, GGTP, alkaline phosphatase and serum cholesterol was established. Conclusion. In 75 % of children with allergic dermatoses, an organic pathology of the upper gastrointestinal tract was diagnosed, thus, a gastroenterological examination should be recommended to all patients.

Background: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival., Methods: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma., Results: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening., Conclusion: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: High-quality gastroscopy is critical for early diagnosis of upper gastrointestinal cancers (UGCs), and assessment of missed cancers may serve as a key quality metric. Using a prospective gastroscopy database and data linkage with the Queensland Cancer Registry, we assessed the risk of developing UGC within 3 years of a cancer-negative gastroscopy at an Australian tertiary centre. Additional aims were to identify factors predictive of missed cancer, perform root cause analyses for missed cancers and assess overall survival., Design/method: We identified patients who were diagnosed with UGC within 3 years of undergoing gastroscopy between 2011 and 2016. Non-mucosal cancers, cancers distal to duodenum and patients undergoing surveillance were excluded. Cases diagnosed within 6 months of gastroscopy were defined as detected cancers, while those developing within 6-36 months were defined as missed cancers. Post-endoscopy UGC rate (PEUGIC-3Y) was calculated as ratio of missed over total cancers detected. Demographic, clinical, endoscopic and histologic variables were analysed., Results: A total of 17,131 gastroscopies were performed for 10,393 patients during the study period. One hundred and twenty-six UGCs were diagnosed, including 120 detected UGCs and 6 missed UGCs. The overall PEUGIC-3Y rate was 4.8% (95% CI 2.1-10.4). The missed UGCs included 3 gastric adenocarcinomas, 2 gastro-oesophageal junction adenocarcinomas and 1 oesophageal squamous cell carcinoma. At the preceding 'cancer-negative gastroscopy', no macroscopic abnormalities were detected at the site of future UGC in 5/6 patients. A UGC developed in 2/6 patients despite an apparent adequate examination at index gastroscopy. Age, sex, indication for endoscopy and cancer location or histology were not predictive of missed cases, and survival was comparable between groups., Conclusion: We demonstrate that the PEUGIC-3Y rate was 4.8% (95% CI 2.1-10.4). The majority of missed cases were adenocarcinomas of the gastro-oesophageal junction or stomach and developed in segments which were found to be normal at index gastroscopy, highlighting the challenges in detecting subtle mucosal lesions in the upper gastrointestinal tract. While overall survival between patients with detected and post-gastroscopy cancers was comparable, these ultimately represent potential missed opportunities for diagnosing an early cancer and underscore the need for quality improvement in gastroscopy., (© 2022. Crown.)

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Kaposi sarcoma (KS) is a low-grade vascular tumor caused by human herpes virus type 8 (HHV8). Gastrointestinal involvement of KS is rare and most commonly clinically silent. Gastrointestinal KS may mimic gastrointestinal stromal tumors (GISTs) histologically as the tumor formed by morphologically spindle-shaped cells, which is mostly located in the mucosa and submucosa. In the present study, we describe a case of Kaposi sarcoma that was first diagnosed in the gastrointestinal tract of a 73-year-old female patient who presented to the clinic with nausea and diarrhea. Immunohistochemical staining showed cytoplasmic CD117 expression both in stomach and colon biopsies. Although involvement of KS is rarely seen in the gastrointestinal tract (GIT), the differential diagnosis of low-grade spindle cell lesions without significant pleomorphism, KS should definitely be considered, and it should be known that CD117 positivity is also present in these neoplasms., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Iron-deficiency anemia is a prevalent condition usually treated with iron supplementation. Iron pill-induced gastritis is an under-recognized, albeit serious potential complication of iron pill ingestion in the upper gastrointestinal tract. This entity must be identified by healthcare providers who prescribe iron. The diagnosis of this unusual drug-induced disease is based on endoscopic findings and histopathological examination, because the clinical symptoms are vague and non-specific. Herein we report a case of a 79-year-old woman with iron-deficiency anemia taking oral ferrous sulfate with multiple congestive and eroded polypoid lesions. Histology showed an H. pylori-negative erosive gastritis with iron deposition, confirming the diagnosis of iron pill-induced gastritis. The aim of this report is to highlight that iron pill-induced gastritis is an under-diagnosed entity that must be kept in mind when patients undergo chronic iron-pill therapy because it can lead to serious complications of the upper gastrointestinal tract.

Graft-versus-host disease (GvHD) involving the intestine is a threat to patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). We evaluated biopsies from different sites of the upper gastrointestinal tract (GIT) of 97 patients after alloHSCT. Forty-six patients with clinical symptoms consistent with upper GI GvHD revealed histological features of GvHD in the esophagus, stomach, and/or duodenum. Biopsies of the duodenum and esophagus were significantly more sensitive for signs of GvHD than those of the gastric antrum or corpus. The histological features of GvHD were significantly correlated with the endoscopic findings of ulcers, erosion, atrophy, and white plaques; however, the sensitivity and specificity of the latter were low. In univariate analysis, overall mortality was significantly associated with histological GvHD signs in all four sites. Nonrelapse mortality was associated with histologic GvHD features in the antrum only. Regarding GvHD diagnosis, biopsies of the upper gastrointestinal tract should include the duodenum and/or esophagus.

Crohn's disease (CD) may affect the entire gastrointestinal tract including its upper part. However, this aspect is poorly addressed in scientific literature and considered a rare finding. Here we aimed to prospectively investigate the prevalence, characteristics and clinical significance of upper gastrointestinal tract involvement in patients with CD, with particular focus on stomach bamboo joint-like appearance (BJA), Helicobacter pylori status and presence of microscopic changes. 375 prospectively recruited patients were included. In CD patients the prevalence of gastric and duodenal, but not esophageal, mucosal lesions, such as gastric mucosal inflammation, duodenal edema, ulcerations, and duodenal bulb deformation was significantly higher (at least p < 0.01 for all). Similar results were found when only H. pylori negative individuals were analyzed. Moreover, BJA of the stomach and in case of H. pylori negative patients also duodenal bulb deformation were detected exclusively in CD patients. Presence of BJA lesion was not significantly associated with neither duration of the disease nor use/history of biologic treatment. Despite absence of H. pylori infection microscopic features of chronic gastritis were found in almost all (93.5%) patients, and in 31% of controls (p < 0.00001). Our analysis outlines that upper gastrointestinal tract involvement in CD is a very common event and frequently manifests with a highly specific BJA lesion. Furthermore, our study reveals that in almost all CD patients features of H. pylori negative gastritis are present., (© 2023. The Author(s).)

Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review. Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm. Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the "Oesophageal Cancer Belt". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies. Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the adenomatous polyposis coli ( APC ) gene. Patients with FAP develop up to thousands of colorectal adenomas as well as lesions in the upper GI tract. In FAP, the upper digestive lesions include gastric fundic gland polyps (FGPs), antrum adenomas, duodenal or small intestinal adenomas, and carcinoma. Patients, after colectomy, are still at significant risk for extracolonic malignancies. Advances in endoscope resolution and optical enhancement technologies allow endoscopists to provide assessments of benign and malignant polyps. For this reason, in the past decades, endoscopic resection techniques have become the first line of treatment in patients with polyps in the upper GI, whereby polyps and even early cancers can be successfully cured. In FAP patients, endoscopic ampullectomy appears to be a safe and effective way of treating patients with ampullary tumors. According to current indications, endoscopic retrograde cholangiopancreatography (ERCP) and stenting of the main pancreatic duct follow ampullectomy.

Introduction: Hypertrophic olivary degeneration (HOD) is a unique form of trans-synaptic neuronal degeneration within the dentato-rubro-olivary pathway which is manifested by the enlargement and hyperintensities of the inferior olivary nucleus in the brain magnetic resonance imaging., Case Report: We report a 53-year-old man admitted to our emergency department with a history of progressive ataxia and vertigo for 6 months before admission. Neurological examination revealed cerebellar dysfunction, and the brain magnetic resonance imaging showed bilateral HOD without an identifiable causative lesion within the brain or abnormal meningeal enhancement. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis, elevated protein, and negative cytology. Malignancy and paraneoplastic workup exhibited marked elevation of carbohydrate antigen 19-9 level and para-aortic lymphadenopathy. A histologic examination demonstrated the infiltration of lymph nodes by a malignant, poorly differentiated carcinomatous tumor that arises from the upper gastrointestinal tract. Considering the primary site of the tumor and HOD as a paraneoplastic effect of carcinoma, a FOLFIRINOX regimen, intravenous immunoglobulin, and pulse methylprednisolone were started. A follow-up imaging after 3 months depicted a significant resolution of HOD but the neurological status only mildly improved. The patient developed liver and adrenal metastasis over the following 6 months, culminating in his death., Conclusion: This study strengthens a relationship between HOD and malignancy as a paraneoplastic syndrome and provides a new incentive for further researches to confirm this association., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Cancers of the upper gastrointestinal tract remain a major contributor to the global cancer burden. The accurate mapping of tumor margins is of particular importance for curative cancer resection and improvement in overall survival. Current mapping techniques preclude a full resection margin assessment in real time., Objective: To evaluate whether diffuse reflectance spectroscopy (DRS) on gastric and esophageal cancer specimens can differentiate tissue types and provide real-time feedback to the operator., Design, Setting, and Participants: This was a prospective ex vivo validation study. Patients undergoing esophageal or gastric cancer resection were prospectively recruited into the study between July 2020 and July 2021 at Hammersmith Hospital in London, United Kingdom. Tissue specimens were included for patients undergoing elective surgery for either esophageal carcinoma (adenocarcinoma or squamous cell carcinoma) or gastric adenocarcinoma., Exposures: A handheld DRS probe and tracking system was used on freshly resected ex vivo tissue to obtain spectral data. Binary classification, following histopathological validation, was performed using 4 supervised machine learning classifiers., Main Outcomes and Measures: Data were divided into training and testing sets using a stratified 5-fold cross-validation method. Machine learning classifiers were evaluated in terms of sensitivity, specificity, overall accuracy, and the area under the curve., Results: Of 34 included patients, 22 (65%) were male, and the median (range) age was 68 (35-89) years. A total of 14 097 mean spectra for normal and cancerous tissue were collected. For normal vs cancer tissue, the machine learning classifier achieved a mean (SD) overall diagnostic accuracy of 93.86% (0.66) for stomach tissue and 96.22% (0.50) for esophageal tissue and achieved a mean (SD) sensitivity and specificity of 91.31% (1.5) and 95.13% (0.8), respectively, for stomach tissue and of 94.60% (0.9) and 97.28% (0.6) for esophagus tissue. Real-time tissue tracking and classification was achieved and presented live on screen., Conclusions and Relevance: This study provides ex vivo validation of the DRS technology for real-time differentiation of gastric and esophageal cancer from healthy tissue using machine learning with high accuracy. As such, it is a step toward the development of a real-time in vivo tumor mapping tool for esophageal and gastric cancers that can aid decision-making of resection margins intraoperatively.

The importance of the assessment of the N‑status in gastric carcinoma, tumors of the gastroesophageal junction and esophageal cancer is undisputed; however, there is currently no internationally validated method for lymph node mapping in esophageal and gastric cancer. Near-infrared fluorescence imaging (NIR) is an innovative technique from the field of vibrational spectroscopy, which in combination with the fluorescent dye indocyanine green (ICG) enables intraoperative real-time visualization of anatomical structures. The ICG currently has four fields of application in oncological surgery: intraoperative real-time angiography for visualization of perfusion, lymphography for visualization of lymphatic vessels, visualization of solid tumors, and (sentinel) lymph node mapping. For imaging of the lymph drainage area and therefore the consecutive lymph nodes, peritumoral injection of ICG must be performed. Several studies have demonstrated the feasibility of peritumoral injection of ICG administered 15 min to 3 days preoperatively with subsequent intraoperative visualization of the lymph nodes. So far prospective randomized studies on the validation of the method are still lacking. In contrast, the use of ICG for lymph node mapping and visualization of sentinel lymph nodes in gastric cancer has been performed in large cohorts as well as in prospective randomized settings. Up to now, multicenter studies for ICG-guided lymph node mapping during oncological surgery of the upper gastrointestinal tract are lacking. Artificial intelligence methods can help to evaluate these techniques in an automated manner in the future as well as to support intraoperative decision making and therefore to improve the quality of oncological surgery., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Assessment of the upper gastrointestinal tract (UGI) may enable more personalized treatment strategies in pediatric inflammatory bowel disease (IBD). However, data on the frequency and significance of these findings remain limited., Methods: Data on 132 pediatric IBD patients with systematic UGI sampling were collected and the baseline characteristics and presence of complications compared between those with and without histological UGI findings. The control group comprised 162 children who received no diagnoses., Results: Seventy-six children had ulcerative colitis (UC), 47 Crohn's disease (CD) and nine IBD unclassified. UGI findings were more common in IBD patients than controls (69.7% vs. 30.9%, respectively, p  < .001), particularly in the stomach (62.1% vs. 16.8%; p  < .001). Among IBD patients, findings were more common in CD than in UC (80.9% vs. 63.2%; p  = .038), particularly in the duodenum (21.3% vs. 2.6%, p  = .001). Four patients had UGI granulomas consistent with CD. Hypoalbuminemia (OR 3.22; 95% CI 1.18-8.79) and failure to thrive (2.82; 1.17-6.78) increased the likelihood of UGI findings in IBD. In CD, perianal morbidity was less common in those with than in those without UGI findings (13.2% vs. 44.4%; p  = .032) whereas in UC, UGI findings increased the risk for co-morbidities (18.8% vs. 3.6%; p  = .059). The long-term outcomes did not differ between patients with or without UGI findings., Conclusions: Histologic UGI findings were more common in children with IBD than in children with no gastrointestinal diagnoses. In CD, UGI findings were more frequent than in UC, especially in the duodenum. In UC, UGI findings were associated with more complex disease.

Background: Heterotopic pancreas (HP) is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract. While the majority of heterotopic pancreatic lesions are asymptomatic, many manifest severe clinical symptoms which require surgical or endoscopic intervention. Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature. The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease., Aim: To classify the common clinical manifestations of heterotopic pancreas., Methods: A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018. Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location. Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated. These were compared to a systematic review of the literature utilizing PubMed and Embase searches for papers pertaining to heterotopic pancreas. Publications describing symptomatic presentation of HP were selected for review. Information including demographics, symptoms, presentation and treatment were compiled and analyzed., Results: Twenty-nine patient were identified with HP at a single center, with six of these identified has having clinical symptoms. Clinical manifestations included, gastrointestinal bleeding, gastric ulceration with/without perforation, pancreatitis, and gastric outlet obstruction. Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients. Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients. The majority of patients presented with abdominal pain (67%) combined with one of the following clinical categories: (1) Dyspepsia, ( n = 445, 48%); (2) Pancreatitis ( n = 260, 28%); (3) Gastrointestinal bleeding ( n = 80, 9%); and (4) Gastric outlet obstruction ( n = 80, 9%). The majority of cases ( n = 832, 90%) underwent surgical or endoscopic resection with 85% reporting resolution or improvement in their symptoms., Conclusion: Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract. Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation., Competing Interests: Conflict-of-interest statement: The authors of this study have no related conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Upper gastrointestinal (GI) neoplasia account for 35% of GI cancers and 1.5 million cancer-related deaths every year. Despite its efficacy in preventing cancer mortality, diagnostic upper GI endoscopy is affected by a substantial miss rate of neoplastic lesions due to failure to recognize a visible lesion or imperfect navigation. This may be offset by the real-time application of artificial intelligence (AI) for detection (computer-aided detection [CADe]) and characterization (computer-aided diagnosis [CADx]) of upper GI neoplasia. Stand-alone performance of CADe for esophageal squamous cell neoplasia, Barrett's esophagus-related neoplasia, and gastric cancer showed promising accuracy, sensitivity ranging between 83% and 93%. However, incorporation of CADe/CADx in clinical practice depends on several factors, such as possible bias in the training or validation phases of these algorithms, its interaction with human endoscopists, and clinical implications of false-positive results. The aim of this review is to guide the clinician across the multiple steps of AI development in clinical practice., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aims: Upper gastrointestinal Crohn's disease (UGI-CD) is an important subclassification of Crohn's Disease (CD). We performed a systematic review and meta-analysis to evaluate the prevalence, risk factors, and clinical outcomes associated with UGI-CD., Methods: We searched Embase and Medline for articles reporting the clinical information of UGI-CD in CD patients, through 27 October 2020. Disease location and phenotype were coded according to the Montreal classification, and results were pooled with random effects by DerSimonian and Laird model., Results: 26 articles were included. The prevalence of UGI-CD was 13%. UGI-CD was most commonly found in the stomach (56%) and was associated with concurrent ileocolonic involvement (54%). Non-stricturing, non-penetrating UGI-CD was the most common behavioral phenotype (61%). L4-jejunal disease was associated with the highest rates of surgery. Region of origin did not significantly influence the location and phenotype of UGI-CD. Young, male patients presenting with erythema nodosum, aphthous ulcers and stricturing-phenotype are more likely to have UGI-CD, which in turn is linked to increased risk of hospitalization and surgery., Conclusion: UGI-CD is present in 13% of patients with CD, and patients with L4-jejunal disease are more likely to require surgery. Further studies examining the effect of ethnicity and region on UGI-CD are needed., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Children with disorders affecting the sensory and motor functions of the esophagus will present primarily with swallowing dysfunction, dysphagia, and chest pain, and those with disorders affecting the normal function of the stomach will present with symptoms like abdominal pain, nausea, and vomiting. Recent advances in the mechanisms of disease and technology have increased our understanding of gastrointestinal physiology and that knowledge has been applied to develop new diagnostic studies and therapeutic interventions. We present an overview of the clinical presentation, diagnosis, and treatment of common primary and secondary functional and motility disorders affecting the upper gastrointestinal tract in children., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Upper gastrointestinal tract pathology observed at autopsy in 94 patients with end-stage renal disease (GFR<10 ml/min) was analysed retrospectively. To better evaluate the effect of haemodialysis on this pathology, the chronic renal failure patients were subdivided into three groups: 19 patients who had died before haemodialysis treatment could be undertaken (group I), 21 patients who had died during the first month (group II), and 54 patients who had died after at least one month of haemodialysis treatment (group III). The results revealed that the number of patients with upper gastrointestinal tract pathology was significantly higher in groups I and II (58% and 57% respectively) as compared to group III (31%) and controls (35%). No difference could be demonstrated between group III and controls. The most prevalent lesions observed were gastritis, followed by gastric and peptic ulcers. The incidence of this pathology appeared to decline as the duration of dialysis therapy increased. Mortality caused by upper gastrointestinal tract pathology remained high during the first two years of treatment in group III, despite a smaller incidence of upper tract lesions. This was explained by a relatively higher proportion of haemorrhage. [ABSTRACT FROM PUBLISHER]

Background: Preoperative nutrition intervention is recommended prior to upper gastrointestinal (UGI) cancer resection; however, there is limited understanding of interventions received in current clinical practice. This study investigated type and frequency of preoperative dietetics intervention and nutrition support received and clinical and demographic factors associated with receipt of intervention. Associations between intervention and preoperative weight loss, surgical length of stay (LOS), and complications were also investigated., Methods: The NOURISH Point Prevalence Study was conducted between September 2019 and May 2020 across 27 Australian tertiary centres. Subjective global assessment and weight were performed within 7 days of admission. Patients reported on preoperative dietetics and nutrition intervention, and surgical LOS and complications were recorded., Results: Two-hundred patients participated (59% male, mean (standard deviation) age 67 (10)). Sixty percent had seen a dietitian preoperatively, whilst 50% were receiving nutrition support (92% oral nutrition support (ONS)). Patients undergoing pancreatic surgery were less likely to receive dietetics intervention and nutrition support than oesophageal or gastric surgeries ( p < 0.001 and p = 0.029, respectively). Neoadjuvant therapy ( p = 0.003) and malnutrition ( p = 0.046) remained independently associated with receiving dietetics intervention; however, 31.3% of malnourished patients had not seen a dietitian. Patients who received ≥3 dietetics appointments had lower mean (SD) percentage weight loss at the 1-month preoperative timeframe compared with patients who received 0-2 appointments (1.2 (2.0) vs. 3.1 (3.3), p = 0.001). Patients who received ONS for >2 weeks had lower mean (SD) percentage weight loss than those who did not (1.2 (1.8) vs. 2.9 (3.4), p = 0.001). In malnourished patients, total dietetics appointments ≥3 was independently associated with reduced surgical complications (odds ratio 0.2, 95% confidence interval (CI) 0.1, 0.9, p = 0.04), and ONS >2 weeks was associated with reduced LOS (regression coefficient -7.3, 95% CI -14.3, -0.3, p = 0.04)., Conclusions: Despite recommendations, there are low rates of preoperative dietetics consultation and nutrition support in this population, which are associated with increased preoperative weight loss and risk of increased LOS and complications in malnourished patients. The results of this study provide insights into evidence-practice gaps for improvement and data to support further research regarding optimal methods of preoperative nutrition support.

To evaluate percutaneous transsplenic varices embolization (PTSVE) in the treatment of upper gastrointestinal bleeding (UGIB) in patients with chronic hepatic schistosomiasis japonicum (CHS), 29 CHS patients (20 males and 9 females) complicated with UGIB were selected as the investigation subjects. The patients were treated by PTSVE under the guidance of X-ray fluoroscopy. The success rate of PTSVE and the rate of complications were observed. In addition, the degrees of varices before and after PTSVE were evaluated by abdominal computed tomography (CT). Results showed that 26 CHS patients (89.6%) were successfully treated with PTSVE. Three cases (10.3%) failed, and two experienced intraperitoneal bleeding within 1 week after PTSVE. The abdominal CT showed a significant decrease of the varices stage in coronary (P < 0.001), esophageal (P = 0.006), and paraesophageal (P = 0.013) varices, but slightly increased perisplenic varices within 1 month of the intervention (P = 0.014). PTSVE may be a safe and effective procedure for the treatment of UGIB in CHS patients, particularly suitable for those with a widened hepatic fissure and exposed hepatic portal vein trunk and an enlarged spleen.

Background and Aim: Rapid on-site evaluation (ROSE) can improve adequacy rates of fine needle aspiration (FNA) and thus save operational costs. Our aim was to assess the cost-efficacy of ROSE performed during endoscopic ultrasound (EUS)-FNA of gastrointestinal lesions., Method: This was a retrospective cohort study of 156 patients who underwent EUS-FNA for pancreatic, submucosal upper gastrointestinal, and adjacent lesions at Galilee Medical Center between 2012 and 2017. The patient cohort was divided into group A (62 patients, 39.7%) who underwent EUS-FNA with ROSE, and group B (94 patients, 60.3%) without ROSE. Cost analysis was based on the additional expenditure of repeated EUS-FNA sessions needed to reach accurate and final diagnosis in the two groups., Results: The overall cost was significantly higher in group B ($121 422) as compared to group A ($72 861), including the ROSE cost. Additional EUS-FNA sessions were needed in 11.3% and 23.4% in groups A and B, respectively. The additional cost to achieve final pathological diagnosis was $7203 and $24 696 in groups A and B, respectively (P = .02), yielding a savings of $252 per EUS-FNA case by adding ROSE. Notably, adding ROSE to the EUS-FNA exam for gastrointestinal non-pancreatic lesions resulted in even higher savings per case ($682.40). Moreover, adding ROSE improved specimen adequacy to achieve final pathological diagnosis (odds ratio = 7.13, P = .0005)., Conclusions: EUS-FNA with ROSE was cost-effective. Incorporating ROSE into the clinical practice of EUS-FNA saves costs and improves specimen adequacy., (© 2021 John Wiley & Sons Ltd.)

Helicobacter pylori infection does not belong to the spectrum of opportunistic infections in people living with HIV (PLHIV). To evaluate the Helicobacter pylori infection prevalence rate trends in HIV co-infected individuals in comparison to the HIV-negative population, we compared histopathological findings of H. pylori positive gastritis (gastritis topography and histopathology) between 303 PLHIV and 2642 HIV-negative patients who underwent esophagogastroduodenoscopy (EGD) between 1993 and 2014 due to dyspeptic symptoms. The prevalence of H. pylori infection was significantly higher in HIV-negative controls than in PLHIV (50.2% vs. 28.1%). A significantly positive linear trend of H. pylori co-infection in PLHIV was revealed in the observed period (b = 0.030, SE = 0.011, p = 0.013), while this trend was significantly negative in HIV-negative patients (b = - 0.027, SE = 0.003, p < 0.001). Patients with HIV/H. pylori co-infection had significantly higher CD4+ T cell counts and more often had undetectable HIV viremia, due to successful anti-retroviral therapy (ART). Stomach histopathological findings differed between HIV co-infected and H. pylori mono-infected patients. Our findings confirm that the ART has changed the progression of HIV infection, leading to a significant increase in the prevalence of H. pylori infection in dyspeptic PLHIV over time. Our data also suggests that a functional immune system may be needed for H. pylori-induced human gastric mucosa inflammation., Competing Interests: The authors have declared that no competing interests exist.

The upper gastrointestinal tract, consisting of the esophagus, stomach, and duodenum, controls food transport, digestion, nutrient uptake, and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly define their distinct cell types. We identify a quiescent COL17A1 high KRT15 high stem/progenitor cell population in the most basal cell layer of the esophagus and detect substantial gene expression differences between identical cell types of the human and mouse stomach. Selective expression of BEST4, CFTR, guanylin, and uroguanylin identifies a rare duodenal cell type, referred to as BCHE cell, which likely mediates high-volume fluid secretion because of continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from duodenal enterochromaffin cells. We, furthermore, discover that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, yet another member of the enteroendocrine hormone family., Competing Interests: Declaration of interests H.C. is an inventor on several patents related to organoid technology; his full disclosure is given at https://www.uu.nl/staff/JCClevers/., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The advent of endoscopy and endoscopic biopsy has greatly facilitated the detection and diagnosis of gastrointestinal neoplasms. Brush cytology often complements and increases the sensitivity and specificity of detection of GIT lesions in many ways., Materials and Methods: The present prospective study was conducted in the Department of Pathology in collaboration with Department of Gastroenterology at S.G.T. Medical College and University, Gurugram. A total of 50 patients suspected of having upper gastrointestinal malignancies formed the study group. After taking the detailed history, patients were subjected to endoscopy using flexible video endoscope. After brushing, biopsies were taken from the lesions and preserved in 10% formalin. The aim of the study was to evaluate the utility of endoscopic brush cytology in diagnosing upper gastrointestinal malignancies and its comparison with endoscopic biopsy., Results: In the present study, a total of 50 cases constituted the study group, during the period of 2018-2019, with the age of patients ranging from 30 to 85 years. Mean age at presentation was 58 years. The most frequent age group affected was 41-60 (44%) and most of them were men (66%). The sensitivity and positive predictive value in our study is 84.4% and 97.4%, respectively, while the specificity and negative predictive value is 100% and 50%, respectively., Conclusion: To conclude, brush cytology is a reliable, simple, safe, rapid, noninvasive yet effective, and inexpensive method of detecting malignancy of upper gastrointestinal tract., (© 2020 Wiley Periodicals LLC.)

Context.—: Immune checkpoint inhibitor (CPI) therapies are associated with multi-organ immune-related adverse events. Although colonic mucosal changes have been described, inflammatory changes incited by CPIs in the upper gastrointestinal tract have not been well characterized., Objective.—: To investigate morphologic and immunologic changes incited by CPI therapy in the upper gastrointestinal tract., Design.—: We compared the morphology and immune cell phenotype of gastric and duodenal biopsies from patients treated with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) or anti-programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) antibodies with biopsies from patients with Helicobacter pylori gastritis, patients with celiac disease, and normal controls., Results.—: Gastric biopsies from patients on CPIs showed chronic gastritis mimicking H pylori gastritis. However, CPI gastritis demonstrated greater numbers of CD8+ intraepithelial lymphocytes, less lamina propria inflammation, fewer plasma cells and CD20+ B cells, fewer lymphoid aggregates, and reduced CD4:CD8 ratio in both the lamina propria and the epithelial layer. There were no differences between anti-CTLA-4 and anti-PD-1/PD-L1 gastritis, except for more lymphoid aggregates in anti-PD-1/PD-L1 gastritis. Duodenal biopsies from patients on CPIs revealed chronic duodenitis with villous blunting, mimicking celiac disease. Compared with celiac disease, CPI duodenitis demonstrated higher prevalence of neutrophilic infiltrates and erosions, increased lamina propria CD3 and CD8 T cells, and reduced CD4:CD8 ratio. Upper gastrointestinal biopsies were more inflamed than concomitant colonic biopsies in the majority of patients., Conclusions.—: The morphologic and immunophenotypic distinctions between CPI-associated upper gastrointestinal injuries and common infectious and autoimmune diseases may provide useful discriminators when clinicians are confronted with gastric and duodenal inflammatory changes in patients receiving CPI therapy., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article.

Background: Mesenchymal tumors (MTs) of upper gastrointestinal tract (UGIT) can show morphologic overlap thus posing a diagnostic challenge. This study evaluated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology in the diagnosis of UGIT-MTs and impact of rapid onsite evaluation (ROSE)., Methods: We retrospectively search our electronic database between January 2001 and August 2019 for cases that underwent EUS-FNA for a submucosal/or intramural upper GI tract mass forming lesions. Data pertinent to immunostain expression in UGIT-MTs was also collected., Results: We identified 139 cases, of which 72 cases had subsequent surgical resection. The cytologic diagnoses included nondiagnostic, negative, atypical, suspicious for neoplasm and positive for neoplasm (PFN) in 11, 7, 11, 10, and 100 cases, respectively. Diagnosis of PFN was rendered in 51 of 69 cases with ROSE (74%) and in 49 of 70 cases without ROSE (70%). However, the cases with ROSE had a higher percentage of cases being precisely classified than without ROSE (86% vs 61%, P < .05). On comparison of cytologic cases with cell block (CB) (n = 118) and without CB (n = 21), ROSE was performed in 67 (57%) and 2 (10%) cases, respectively (P < .01). All the cases with diagnosis of PFN were confirmed on subsequent surgical resection., Conclusion: EUS-FNA has a diagnostic yield of 72% for UGIT-MTs. ROSE could improve diagnostic performance by further classifying MTs, probably via securing adequate lesional material for cell block for additional ancillary testing and precise diagnosis., (© 2020 Wiley Periodicals LLC.)

Reactivation of latent varicella zoster virus (VZV) may be limited to a dermatome or involve multiple organs, including the gastrointestinal tract. Although gastrointestinal manifestations of disseminated zoster have been likened to those of herpes simplex virus (HSV), histologic features of VZV-related injury to the tubular gut are not well-documented. We performed this study to describe the clinicopathologic features of VZV-related gastrointestinal injury. We identified 6 such patients with VZV infection. All involved the upper gastrointestinal tract, affecting the esophagus (n=3), stomach (n=2), or both (n=1). All patients were immunocompromised adults with hematologic malignancies (n=5) or a heart transplant (n=1); 3 with hematologic malignancies had received stem cell transplants. Five patients had cutaneous and gastrointestinal zoster; 1 had gastrointestinal disease alone. When compared with 14 HSV-related esophagitis controls, there were several notable differences. VZV caused hemorrhagic ulcers with nodularity or erythema, whereas HSV produced round, shallow ulcers on a background of nearly normal mucosa (P=0.01). VZV-related ulcers featured fibrin-rich, pauci-inflammatory exudates compared with the macrophage-rich exudates of HSV (P=0.003). The cytopathic changes of VZV were present at all levels of the squamous epithelium, especially in a peripapillary distribution. In contrast, HSV inclusions were located in the superficial layers (P=0.003) and detached keratinocytes. Unlike HSV, VZV involved the stomach, producing hemorrhage accompanied by striking apoptosis in the deep glands. We conclude that VZV produces unique patterns of gastrointestinal injury that facilitate its diagnosis. Recognition of gastrointestinal VZV infection is important because it heralds potentially life-threatening disseminated disease., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with metachronous malignancies before carcinomas of the upper gastrointestinal tract were analyzed regarding clinical parameters, oncological outcome, and prognosis., Methods: We analyzed the data of 1583 patients with gastroesophageal cancer who underwent oncological resections between 2002 and 2018. Of 1583 patients, 172 had a malignant tumor before the upper gastrointestinal cancer (second primary carcinomas) and 1411 without preceding malignancies served as the control group. The analyses were performed between both groups and within the subgroup of second primary carcinomas., Results: Patients with second primary carcinomas were older (P < 0.0001), had more comorbidities (P < 0.0001), and underwent longer surgical resections (P = 0.0024). They had lower (y)pT-categories (P = 0.0427) and had longer stays in intensive care unit (P = 0.0002) and hospital (P = 0.0018). R0-resection was more frequent (P = 0.0275) while having more surgical complications (P = 0.0378). The median survival was 39.5 mo (primary carcinoma) versus 32.9 mo for (second primary carcinoma) and was not significantly different (P = 0.5359).In the subgroup analysis of second primaries, there were no significant survival differences depending on primary tumor entity (P = 0.4989). pT status (P = 0.0062), pN status (P < 0.0001), pM status (P < 0.0001), and R-status (P < 0.0001) were significant prognostic factors. A time period >9 y after the primary cancer could be identified as a novel and beneficial survival factor (P = 0.0496). Most patients with primary colorectal, prostate, hematogenous, or breast cancer had adenocarcinoma, whereas patients with initial otolaryngologic cancers mainly had squamous cell carcinoma., Conclusions: Second primary carcinomas of the upper gastrointestinal tract show distinct clinical and oncological characteristics. Common prognostic factors are applicable, and oncologic resection is recommended., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10-15%, compared to melanoma at 20-40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract.

A broad spectrum of pathogens produce gastrointestinal disease. The ongoing spread of human immunodeficiency virus/acquired immune deficiency syndrome, the increased use of immunosuppressive therapy and the persistence of overcrowding and suboptimal sanitation in underdeveloped areas facilitate both disease transmission from environmental and foodborne sources and person-to-person transmission. Clinicians increasingly rely on endoscopic biopsy sample interpretation to diagnose gastrointestinal infections. Thus, pathologists must be aware of diagnostic features of a variety of microbial pathogens. Detection with molecular techniques also allows for correlation between infectious agents and their histopathological features, which has expanded our knowledge of the inflammatory changes produced by infectious agents. This review covers infectious disorders of the upper gastrointestinal tract encountered in surgical pathology. Clinical, endoscopic and pathological features are presented. The review emphasises morphological features of viruses, bacteria, fungi and parasites that may be found in tissue samples, and the inflammatory patterns that they produce. Differential diagnoses and useful ancillary techniques are discussed., (© 2020 John Wiley & Sons Ltd.)

Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases., (© 2020 John Wiley & Sons Ltd.)

Aerodigestive adverse effects (AD-AE) during intravenous pentamidine (IV-P) infusion for Pneumocystis jiroveci pneumonia prophylaxis are uncommon in retrospective chart review studies. We conducted a survey in patients on IV-P, which included 31 specific questions. Twenty-five patients were included in the analysis; AD-AE were observed in 22 (88%) with recurrence of symptoms in 88% participants with subsequent infusions. Five leading symptoms were congestion (48%), lip tingling (32%), nausea (28%), tongue tingling (24%), vomiting, and throat swelling (17%); multiple symptoms were reported in 72% of the patients. In conclusion, AD-AE of IV-P infusion are common, self-limited, and tend to be recurrent., (© 2020 Wiley Periodicals LLC.)

Background/aims: A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis., Methods: This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis., Results: Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity., Conclusions: This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In pediatric Crohn's disease (CD) patients, it is important to define the disease phenotype at diagnosis for stratifying risk. In this retrospective study, we aimed to assess the disease phenotype compared to EUROKIDS registry and analyze disease outcome of pediatric CD patients according to upper gastrointestinal (GI) tract involvement. A total of 312 patients were included. The median age at diagnosis was 13.7 years and 232 patients (74.4%) were identified to have upper GI involvement at diagnosis. In Korean pediatric CD patients, there were significant differences in male predominance (72.8% vs. 59.2, p < 0.001), proportion of upper GI involvement (74.4% vs. 46.2%, p < 0.001), and perianal disease (62.1% vs. 8.2%, p < 0.001) compared to data in the EUROKIDS registry. Younger age (OR 2.594, p = 0.0139) and ileal involvement (OR 2.293, p = 0.0176) at diagnosis were associated with upper GI involvement. There were no significant differences in disease outcomes between patients with and without upper GI tract involvement. This study revealed that upper GI involvement is more prevalent in Korean patients with pediatric Crohn's disease than in European patients, and the disease outcome did not appear to differ according to upper GI tract involvement.