Summary The role of putative preneoplastic enterochromaffin-like cell lesions, either hyperplastic or dysplastic, in the genesis of type 1 enterochromaffin-like cell neuroendocrine tumors associated ...with type A chronic atrophic gastritis, their actual neoplastic risk, and their precise histogenetic mechanism deserve further clarification by specific histopathologic studies coupled with patient follow-up. A total of 100 patients with severe type A chronic atrophic gastritis, enterochromaffin-like cell hyperplasia, and antral G-cell hyperplasia were endoscopically and histologically followed up for a median of 90.1 months (total of 9118 person-months). Preneoplastic enterochromaffin-like cell lesions and newly developed neuroendocrine tumors were investigated histologically and histochemically, in parallel with enterochromaffin-like cell lesions found in nontumor mucosa of another 32 well-characterized and previously reported type 1 neuroendocrine tumors. Both neuroendocrine and nonneuroendocrine mucosa changes were analyzed and statistically evaluated. During follow-up, 7 of 100 patients developed neuroendocrine tumors: 5 were in a group of 20 cases with previous enterochromaffin-like cell dysplasia and 2 were among 80 cases showing only enterochromaffin-like cell hyperplasia throughout the study (hazard ratio, 20.7; P < .001). The severity of enterochromaffin-like cell hyperplasia at first biopsy, with special reference to linear hyperplasia with 6 chains or more per linear millimeter, also increased the risk of neuroendocrine tumor development during follow-up (hazard ratio, 13.0; P < .001). Enterochromaffin-like cell microinvasive dysplastic lesions arising at the epithelial renewal zone level, in connection with immature proliferating mucous-neck cells, were found to be linked to early intramucosal neuroendocrine tumor histogenesis. Both enterochromaffin-like cell dysplasia and severe hyperplasia indicate increased risk of neuroendocrine tumor development in type A chronic atrophic gastritis with hypergastrinemia/G-cell hyperplasia.
In both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. ...Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls.
The coronavirus disease 2019 (COVID-19) outbreak has modified the activities of endoscopy units worldwide. Herein, we investigated the impact of the COVID-19 outbreak on anesthesiologist assistance ...for endoscopic procedures in Lombardy, Italy.
A questionnaire concerning anesthesiologist assistance provided from October 26 to December 6, 2020, in comparison with the same period in 2019, was sent to endoscopic units in Lombardy.
Approximately 54% (34/63) of the units responded. A reduction in the number of all endoscopies (-33.5%; 18792 in 2020 vs. 28264 in 2019) and anesthesiologist-assisted endoscopies (-15.3%; 2652 in 2020 vs. 3132 in 2019) was reported. A greater reduction in anesthesiologist assistance was observed in government community units (-29.5%) than in academic (-14%) and private community units (-4.6%). Among all units, 85% reported a reduction in anesthesiologist assistance; 65% observed a delay/cancellation of procedures; 59%, a restricted patient selection; 17%, the need to transfer some patients to other hospitals; and 32%, a related worsening of procedure quality.
The COVID-19 pandemic compromised the anesthesiologist assistance for endoscopic procedures in Lombardy, which worsened the procedure quality mainly in government community units. The COVID-19 "stress test" suggests a more balanced allocation of anesthesiologic resources in the future.
Abstract Adult autoimmune enteropathy (AIE) is a rare cause of malabsorption syndrome unresponsive to dietary restriction. Its diagnostic hallmarks are small-bowel villous atrophy and antienterocyte ...autoantibodies. Therapy is based mainly on nutritional support and immunosuppression. We treated a 61-year-old woman with corticosteroid-refractory AIE and life-threatening malabsorption syndrome with systemic infusions of autologous, bone marrow–derived, mesenchymal stromal cells (MSCs) as rescue therapy. The MSCs were expanded ex vivo following a previously used Good Manufacturing Practice procedure, and 2 intravenous infusions of 1.8 × 106 MSCs/kg body weight were administered 2 weeks apart. Analysis of circulating and mucosal regulatory T-and B-cell numbers, and of serum and secretory immunoglobulin levels, was performed before and after treatment. The MSC infusions were safe and effective, leading to disappearance of disease hallmarks and recovery from the life-threatening condition. Increases in mucosal regulatory T-cell numbers and secretory immunoglobulin levels were also observed. The benefit, however, was transient, and a further MSC infusion resulted in the same short efficacy. This case encourages the use of MSCs to treat patients with life-threatening, corticosteroid-refractory AIE and suggests that MSC infusion can attenuate, albeit transiently, the autoimmune attack.
External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel ...and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease.
We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×10⁶ MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated.
MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p < 0.01 for both), and rectal mucosal healing were induced by treatment without any adverse effects. The percentage of mucosal and circulating regulatory T cells significantly increased during the treatment and remained stable until the end of follow up (p < 0.0001 and p < 0.01, respectively). Furthermore, MSCs have been proven to affect mucosal T cell apoptotic rate.
Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.
Abstract
Background
Computer-aided detection (CADe) increases adenoma detection in primary screening colonoscopy. The potential benefit of CADe in a fecal immunochemical test (FIT)-based colorectal ...cancer (CRC) screening program is unknown. This study assessed whether use of CADe increases the adenoma detection rate (ADR) in a FIT-based CRC screening program.
Methods
In a multicenter, randomized trial, FIT-positive individuals aged 50–74 years undergoing colonoscopy, were randomized (1:1) to receive high definition white-light (HDWL) colonoscopy, with or without a real-time deep-learning CADe by endoscopists with baseline ADR > 25 %. The primary outcome was ADR. Secondary outcomes were mean number of adenomas per colonoscopy (APC) and advanced adenoma detection rate (advanced-ADR). Subgroup analysis according to baseline endoscopists’ ADR (≤ 40 %, 41 %–45 %, ≥ 46 %) was also performed.
Results
800 individuals (median age 61.0 years interquartile range 55–67; 409 men) were included: 405 underwent CADe-assisted colonoscopy and 395 underwent HDWL colonoscopy alone. ADR and APC were significantly higher in the CADe group than in the HDWL arm: ADR 53.6 % (95 %CI 48.6 %–58.5 %) vs. 45.3 % (95 %CI 40.3 %–50.45 %; RR 1.18; 95 %CI 1.03–1.36); APC 1.13 (SD 1.54) vs. 0.90 (SD 1.32;
P
= 0.03). No significant difference in advanced-ADR was found (18.5 % 95 %CI 14.8 %–22.6 % vs. 15.9 % 95 %CI 12.5 %–19.9 %, respectively). An increase in ADR was observed in all endoscopist groups regardless of baseline ADR.
Conclusions
Incorporating CADe significantly increased ADR and APC in the framework of a FIT-based CRC screening program. The impact of CADe appeared to be consistent regardless of endoscopist baseline ADR.
Abstract Background & aims Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the ...degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin. Methods The transcriptional response of human duodenal mucosa to hepcidin was investigated using organ cultures of duodenal biopsies perendoscopically collected from healthy controls. Biopsies were cultured for 4 hours with or without hepcidin-25 and were then assayed for the expression of iron-related genes. Results In samples that had not been exposed to hepcidin, correlations were found between the expression of genes involved in iron absorption: DMT1 , Fpn1 , Dcytb and HCP1 . In ex vivo experiments hepcidin down-regulated mRNA levels of the iron transporters Fpn1, and DMT1 , of the ferric reductase Dcytb , of the ferroxidase hephaestin , and of the putative heme carrier protein HCP1. Conclusions Through the reported transcriptional changes hepcidin can modulate several steps of the iron absorption process, including the reduction of dietary iron by Dcytb, its uptake by enterocytes through DMT1, the mucosal uptake of heme iron by HCP1, and enterocyte iron release to plasma by Fpn1 in conjunction with hephaestin.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Three causative genes are known: ENG (HHT-1), ...ACVRL1 (HHT-2), and SMAD4 (mutated in HHT in association with juvenile polyposis). Gastrointestinal bleeding is the most common symptom after epistaxis. The stomach and the duodenum are the main gastrointestinal sites of telangiectases. Our aim was to explore gastrointestinal tract of consecutive HHT patients to assess distribution, number, size, and type of telangiectases in relation to genotype.
HHT patients underwent gastroduodenoscopy, video capsule endoscopy, and colonoscopy. Molecular analysis of ENG and ACVRL1 was performed to identify the disease-causing mutation.
Twenty-two patients (13 men; mean age: 59 ± 9 years) were analyzed: 7 with HHT-1, 13 with HHT-2, and 2 undefined. Gastrointestinal telangiectases were identified as follows: at gastroduodenoscopy in 86% of HHT-1 patients and in 77% of HHT-2 patients, at video capsule endoscopy in all HHT-1 patients and in 84% of HHT-2 patients, and at colonoscopy in 1 patient for each group. HHT-1 showed multiple telangiectases with a higher prevalence, more relevant in the duodenum.
Our data demonstrate extensive involvement of the gastrointestinal tract with a more severe association in HHT-1. Gastroduodenoscopy provides significant information on gastrointestinal involvement, and video capsule endoscopy may be added in selected patients. Colonic polyps/adenomas were identified as occasional findings.
Background/Aims: The coronavirus disease 2019 (COVID-19) outbreak has modified the activities of endoscopy units worldwide. Herein, we investigated the impact of the COVID-19 outbreak on ...anesthesiologist assistance for endoscopic procedures in Lombardy, Italy.
Methods: A questionnaire concerning anesthesiologist assistance provided from October 26 to December 6, 2020, in comparison with the same period in 2019, was sent to endoscopic units in Lombardy.
Results: Approximately 54% (34/63) of the units responded. A reduction in the number of all endoscopies (-33.5%; 18792 in 2020 vs. 28264 in 2019) and anesthesiologist-assisted endoscopies (-15.3%; 2652 in 2020 vs. 3132 in 2019) was reported. A greater reduction in anesthesiologist assistance was observed in government community units (-29.5%) than in academic (-14%) and private community units (-4.6%). Among all units, 85% reported a reduction in anesthesiologist assistance; 65% observed a delay/ cancellation of procedures; 59%, a restricted patient selection; 17%, the need to transfer some patients to other hospitals; and 32%, a related worsening of procedure quality.
Conclusion: The COVID-19 pandemic compromised the anesthesiologist assistance for endoscopic procedures in Lombardy, which worsened the procedure quality mainly in government community units. The COVID-19 “stress test” suggests a more balanced allocation of anesthesiologic resources in the future. Clin Endosc 2022;55:49-57
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