Endoscopic Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours: An Overview of Proposed Resection and Ablation Techniques.

A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs.

Treatment options for gastrointestinal bleeding blue rubber bleb nevus syndrome: Systematic review.

OBJECTIVES: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. METHODS: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. RESULTS: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow-up time (P = 0.19) or in the recurrence rate (P = 0.45). CONCLUSION: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported.

The carbon cost of inappropriate endoscopy.

BACKGROUND AND AIMS: Digestive endoscopy is a resource-intensive activity with a conspicuous carbon footprint and an estimated rate of inappropriateness. However, the carbon costs of inappropriate endoscopic procedures still remain obscure. Here we evaluated the environmental impact of inappropriate endoscopic examinations. METHODS: We calculated the carbon cost of a standard endoscopic procedure (EGD and colonoscopy [CLS]), taking into account the items (eg, disposable materials, personal protective equipment) and energy required for the endoscopy procedure itself and the cleaning process. The rates of inappropriateness and the mortality cost of carbon (MCC) of endoscopic examinations in different scenarios were calculated. RESULTS: EGD and CLS presented a carbon cost of 5.43 kg and 6.71 kg of CO2, respectively. Different scenarios were evaluated, according to the number of endoscopic procedures performed in Italy per 1000 inhabitants and the reported data on their inappropriateness. The carbon cost of inappropriate EGD and CLS in Italy was 4133 CO2 metric tons per year (MCC, .93), ranging from 3527 to 4749, and equivalent to 1,760,446 L of gasoline consumed. Applying the same data to the European population, the estimated carbon footprint of inappropriate digestive endoscopy in Europe was 30,804 metric tons. CONCLUSIONS: The environmental impact of inappropriate endoscopic procedures in Europe is remarkable. These results highlight the need to adopt novel strategies aimed at reducing both the carbon footprint of digestive endoscopy and the rate of inappropriate procedures.

Can artificial intelligence replace endoscopists when assessing mucosal healing in ulcerative colitis? A systematic review and diagnostic test accuracy meta-analysis.

BACKGROUNDS AND AIMS: Mucosal healing (MH) in inflammatory bowel diseases (IBD) is an important landmark for clinical decision making. Artificial intelligence systems (AI) that automatically deliver the grade of endoscopic inflammation may solve moderate interobserver agreement and the need of central reading in clinical trials. METHODS: We performed a systematic review of EMBASE and MEDLINE databases up to 01/12/2022 following PRISMA and the Joanna Briggs Institute methodologies to answer the following question: "Can AI replace endoscopists when assessing MH in IBD?". The research was restricted to ulcerative colitis (UC), and a diagnostic odds ratio (DOR) meta-analysis was performed. Risk of bias was evaluated with QUADAS-2 tool. RESULTS: A total of 21 / 739 records were selected for full text evaluation, and 12 were included in the meta-analysis. Deep learning algorithms based on convolutional neural networks architecture achieved a satisfactory performance in evaluating MH on UC, with sensitivity, specificity, DOR and SROC of respectively 0.91(CI95 %:0.86-0.95);0.89(CI95 %:0.84-0.93);92.42(CI95 %:54.22-157.53) and 0.957 when evaluating fixed images (n = 8) and 0.86(CI95 %:0.75-0.93);0.91(CI95 %:0.87-0.94);70.86(CI95 %:24.63-203.86) and 0.941 when evaluating videos (n = 6). Moderate-high levels of heterogeneity were noted, limiting the quality of the evidence. CONCLUSIONS: AI systems showed high potential in detecting MH in UC with optimal diagnostic performance, although moderate-high heterogeneity of the data was noted. Standardised and shared AI training may reduce heterogeneity between systems.

Clinical features of type 1 and 2 refractory celiac disease: Results from a large cohort over a decade.

OBJECTIVES: Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up. METHODS: We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients. RESULTS: Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality. CONCLUSIONS: Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality.

A virtual chromoendoscopy artificial intelligence system to detect endoscopic and histologic activity/remission and predict clinical outcomes in ulcerative colitis.

BACKGROUND: Endoscopic and histological remission (ER, HR) are therapeutic targets in ulcerative colitis (UC). Virtual chromoendoscopy (VCE) improves endoscopic assessment and the prediction of histology; however, interobserver variability limits standardized endoscopic assessment. We aimed to develop an artificial intelligence (AI) tool to distinguish ER/activity, and predict histology and risk of flare from white-light endoscopy (WLE) and VCE videos. METHODS: 1090 endoscopic videos (67 280 frames) from 283 patients were used to develop a convolutional neural network (CNN). UC endoscopic activity was graded by experts using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Paddington International virtual ChromoendoScopy ScOre (PICaSSO). The CNN was trained to distinguish ER/activity on endoscopy videos, and retrained to predict HR/activity, defined according to multiple indices, and predict outcome; CNN and human agreement was measured. RESULTS: The AI system detected ER (UCEIS ≤ 1) in WLE videos with 72 % sensitivity, 87 % specificity, and an area under the receiver operating characteristic curve (AUROC) of 0.85; for detection of ER in VCE videos (PICaSSO ≤ 3), the sensitivity was 79 %, specificity 95 %, and the AUROC 0.94. The prediction of HR was similar between WLE and VCE videos (accuracies ranging from 80 % to 85 %). The model's stratification of risk of flare was similar to that of physician-assessed endoscopy scores. CONCLUSIONS: Our system accurately distinguished ER/activity and predicted HR and clinical outcome from colonoscopy videos. This is the first computer model developed to detect inflammation/healing on VCE using the PICaSSO and the first computer tool to provide endoscopic, histologic, and clinical assessment.

Nomenclature and Definition of Atrophic Lesions in Small Bowel Capsule Endoscopy: A Delphi Consensus Statement of the International CApsule endoscopy REsearch (I-CARE) Group.

(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.

Prothrombin induced by vitamin K absence or antagonist-II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C-related cirrhosis treated with direct-acting antiviral agents.

BACKGROUND: Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown. AIM: To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis. RESULTS: We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P < 0.0001). After 52 (3-66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2-12 868) ng/mL and PIVKA-II 80 (22-1813) mAU/mL. EOT-PIVKA-II (HR 3.05, P < 0.0001) and AFP (HR 2.77, P = 0.001) independently predicted HCC together with diabetes (HR 6.12, P < 0.001) and GGT (HR 1.01, P = 0.03). The 4-year cumulative probability of HCC was 24% vs 2% in patients with EOT-PIVKA-II > or ≤41 mAU/mL (P < 0.0001), and 26% vs 9% for EOT-AFP > or ≤15 ng/mL (P = 0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P < 0.0001). CONCLUSIONS: In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.

Safety and effectiveness of up to 3 years' bulevirtide monotherapy in patients with HDV-related cirrhosis.

The entry inhibitor bulevirtide (BLV) received conditional approval from the EMA in July 2020 for the treatment of adult patients with compensated chronic hepatitis delta. However, the effectiveness and safety of BLV administered as monotherapy beyond 48 weeks in difficult-to-treat patients with HDV-related cirrhosis is presently unknown. Herein, we describe the first patients with HDV-related compensated cirrhosis who were treated with BLV (10 mg/day as a starting dose) for up to 3 years on a compassionate use program. Patients were also monitored for HBcrAg and HBV RNA levels, and HDV- and HBV-specific T-cell markers. In the patient who stopped BLV at week 48, after achieving a virological and biochemical response, the initial virological and biochemical rebound was followed by alanine aminotransferase normalization coupled with low HDV RNA and HBsAg levels. In the 2 patients treated continuously for 3 years, virological and biochemical responses were maintained throughout the treatment period even after dose reduction. In a patient with advanced compensated cirrhosis, liver function tests significantly improved, esophageal varices disappeared, and histological/laboratory features of autoimmune hepatitis resolved. Overall, no safety issues were recorded, as bile salt increase was asymptomatic. While serum HBV RNA levels remained undetectable in all patients, HBV core-related antigen levels showed a progressive, yet modest decline during long-term BLV treatment. No HDV-specific interferon-γ-producing T cells were detected, neither after HDV reactivation (after BLV withdrawn in Patient 1) nor during 3 years of BLV treatment. In conclusion, this report shows that continuous administration of BLV monotherapy for 3 years leads to excellent virological and clinical responses in patients with HDV-related cirrhosis who had contraindications to interferon-based therapies.

Safety and clinical efficacy of the double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicenter cohort study.

Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT-P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX-double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single-switched from originator IFX to CT-P13 was performed, before and after an inverse probability of treatment weighting (IPTW)-based propensity score analysis. Fifty-two double-switched patients with IBD were enrolled. The 24- and 52-week proportions of patients continuing on IFX therapy following the second switch (CTP13 â†’ SB2) were 98% (95% confidence interval [CI] 94%-100%) and 90% (95% CI 81%-99%), respectively. Four patients experienced a total of five AEs, all graded 1-3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24-week and follow-up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double-switch group with a single-switch group of 66 patients with IBD; all these results were confirmed by IPTW-adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT-P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.

Artificial intelligence in gastrointestinal endoscopy for inflammatory bowel disease: a systematic review and new horizons.

INTRODUCTION: Since the advent of artificial intelligence (AI) in clinical studies, luminal gastrointestinal endoscopy has made great progress, especially in the detection and characterization of neoplastic and preneoplastic lesions. Several studies have recently shown the potential of AI-driven endoscopy for the investigation of inflammatory bowel disease (IBD). This systematic review provides an overview of the current position and future potential of AI in IBD endoscopy. METHODS: A systematic search was carried out in PubMed and Scopus up to 2 December 2020 using the following search terms: artificial intelligence, machine learning, computer-aided, inflammatory bowel disease, ulcerative colitis (UC), Crohn's disease (CD). All studies on human digestive endoscopy were included. A qualitative analysis and a narrative description were performed for each selected record according to the Joanna Briggs Institute methodologies and the PRISMA statement. RESULTS: Of 398 identified records, 18 were ultimately included. Two-thirds of these (12/18) were published in 2020 and most were cross-sectional studies (15/18). No relevant bias at the study level was reported, although the risk of publication bias across studies cannot be ruled out at this early stage. Eleven records dealt with UC, five with CD and two with both. Most of the AI systems involved convolutional neural network, random forest and deep neural network architecture. Most studies focused on capsule endoscopy readings in CD (n = 5) and on the AI-assisted assessment of mucosal activity in UC (n = 10) for automated endoscopic scoring or real-time prediction of histological disease. DISCUSSION: AI-assisted endoscopy in IBD is a rapidly evolving research field with promising technical results and additional benefits when tested in an experimental clinical scenario. External validation studies being conducted in large and prospective cohorts in real-life clinical scenarios will help confirm the added value of AI in assessing UC mucosal activity and in CD capsule reading. PLAIN LANGUAGE SUMMARY: Artificial intelligence for inflammatory bowel disease endoscopy Artificial intelligence (AI) is a promising technology in many areas of medicine. In recent years, AI-assisted endoscopy has been introduced into several research fields, including inflammatory bowel disease (IBD) endoscopy, with promising applications that have the potential to revolutionize clinical practice and gastrointestinal endoscopy.We have performed the first systematic review of AI and its application in the field of IBD and endoscopy.A formal process of paper selection and analysis resulted in the assessment of 18 records. Most of these (12/18) were published in 2020 and were cross-sectional studies (15/18). No relevant biases were reported. All studies showed positive results concerning the novel technology evaluated, so the risk of publication bias cannot be ruled out at this early stage.Eleven records dealt with UC, five with CD and two with both. Most studies focused on capsule endoscopy reading in CD patients (n = 5) and on AI-assisted assessment of mucosal activity in UC patients (n = 10) for automated endoscopic scoring and real-time prediction of histological disease.We found that AI-assisted endoscopy in IBD is a rapidly growing research field. All studies indicated promising technical results. When tested in an experimental clinical scenario, AI-assisted endoscopy showed it could potentially improve the management of patients with IBD.Confirmatory evidence from real-life clinical scenarios should be obtained to verify the added value of AI-assisted IBD endoscopy in assessing UC mucosal activity and in CD capsule reading.

Acquired Refractory Iron Deficiency Anemia.

Anemia is a global health problem affecting one-third of the world population, and half of the cases are due to iron deficiency (ID). Iron deficiency anemia (IDA) is the leading cause of disability in several countries. Although multiple mechanisms may coexist, ID and IDA causes can be classified as i) insufficient iron intake for the body requirement, ii) reduced absorption, and iii) blood losses. Oral iron represents the mainstay of IDA treatment. IDA is defined as "refractory" when the hematologic response after 4 to 6 weeks of treatment with oral iron (an increase of >=1 g/dL of Hb) is absent. The cause of iron-refractory anemia is usually acquired and frequently related to gastrointestinal pathologies, although a rare genetic form called iron-refractory iron deficiency anemia (IRIDA) exists. In some pathological circumstances, either genetic or acquired, hepcidin increases, limiting the absorption in the gut, remobilization, and recycling of iron, thereby reducing iron plasma levels. Indeed, conditions with high hepcidin levels are often under-recognized as iron refractory, leading to inappropriate and unsuccessful treatments. This review provides an overview of the iron refractory anemia underlying conditions, from gastrointestinal pathologies to hepcidin dysregulation and iatrogenic or provoked conditions, and the specific diagnostic and treatment approach.

An Unprecedented Challenge: The North Italian Gastroenterologist Response to COVID-19.

BACKGROUND: COVID-19 pandemic has profoundly changed the activities and daily clinical scenarios, subverting organizational requirements of our Gastroenterology Units. AIM: to evaluate the clinical needs and outcomes of the gastroenterological ward metamorphosis during the COVID-19 outbreaks in a high incidence scenario. METHODS: we compared the pertinence of gastroenterological hospitalization, modality of access, mortality rate, days of hospitalization, diagnostic and interventional procedures, age, Charlson comorbidity index, and frequency of SARS-CoV-2 infections in patients and healthcare personnel across the first and the second COVID-19 outbreaks in a COVID-free gastroenterological ward in the metropolitan area of Milan, that was hit first and hardest during the first COVID-19 outbreak since March 2020. RESULTS: pertinence of gastroenterological hospitalization decreased both during the first and, to a lesser degree, the second SARS-CoV2 waves as compared to the pre-COVID era (43.6, 85.4, and 96.2%, respectively), as occurred to the admissions from domicile, while age, comorbidities, length of stay and mortality increased. Endoscopic and interventional radiology procedures declined only during the first wave. Hospitalized patients resulted positive to a SARS-CoV-2 nasopharyngeal swab in 10.2% of cases during the first COVID-19 outbreak after a median of 7 days since admission (range 1-15 days) and only 1 out of 318 patients during the second wave (6 days after admission). During the first wave, 19.5% of healthcare workers tested positive for SARS-CoV-2. CONCLUSIONS: a sudden metamorphosis of the gastroenterological ward was observed during the first COVID-19 outbreak with a marked reduction in the gastroenterological pertinence at the admission, together with an increase in patients' age and multidisciplinary complexity, hospital stays, and mortality, and a substantial risk of developing a SARS-CoV-2 test positivity. This lesson paved the way for the efficiency of hospital safety protocols and admission management, which contributed to the improved outcomes recorded during the second COVID-19 wave.