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Duodenoscope-related infections are a major concern in medicine and GI endoscopy, especially in fragile patients. Disposable duodenoscopes seem to be the right tool to minimize the problem: a good choice for patients with many comorbidities or with a high risk of carrying multidrug resistant bacteria. Urgent endoscopy could also be a good setting for the use of single-use duodenoscopes, especially when the risk of the infection cannot be evaluated. Their safety and efficacy in performing ERCP has been proven in many studies. However, randomized clinical trials and comparative large studies with reusable scopes are lacking. Moreover, the present early stage of their introduction on the market does not allow a large economical evaluation for each health system. Thus, accurate economical and safety comparisons with cap-disposable duodenoscopes are needed. Moreover, the environmental impact of single-use duodenoscopes should be carefully evaluated, considering the ongoing climate change. In conclusion, definitive guidelines are needed to choose wisely the appropriate patients for ERCP with disposable duodenoscopes as the complete switch to single-use duodenoscopes seems to be difficult, to date. Many issues are still open, and they need to be carefully evaluated in further, larger studies.

Background: Magnetic resonance cholangiopancreatography (MRCP) is the gold standard for diagnosis of patients with primary sclerosing cholangitis (PSC). The semi-quantitative MRCP-derived Anali scores proposed for risk stratification, have poor-to-moderate inter-reader agreement., Aims: To evaluate the prognostic performance of quantitative MRCP metrics in PSC., Methods: This is a retrospective study of PSC patients undergoing MRCP. Images were processed using MRCP+ software (Perspectum Ltd, Oxford) that provides quantitative biliary features, semi-automatically extracted by artificial intelligence-driven analysis of MRCP-3D images. The prognostic value of biliary features has been assessed for all hepato-biliary complications., Results: 87 PSC patients have been included in the analysis. Median follow-up from MRCP to event/censoring of 30.9 months (Q1-Q3=13.6-46.6). An adverse outcome occurred in 27 (31.0%) patients. The number of biliary strictures (HR=1.05 per unit, 95%CI 1.02-1.08, p < 0.0001), spleen length (HR=1.16 per cm, 95%CI 1.01-1.34, p = 0.039), adjusted for height, age at MRCP, and time from diagnosis to MRCP predicted higher risk of hepatobiliary complications. These were incorporated into a the quantitative MRCP-derived PSC (qMRCP-PSC) score (C-statistic=0.80). After 3-fold cross-validation, qMRCP-PSC outperformed the Anali score in our cohort (C-statistic of 0.78 vs 0.64) and enabled the discrimination of survival of PSC patients (log-rank p < 0.0001)., Conclusions: The qMRCP-PSC score identified patients at higher risk of hepatobiliary complications and outperformed the available radiological scores. It represents a novel quantitative biomarker for disease monitoring and a potential surrogate endpoint for clinical trials., Competing Interests: Declaration of Competing Interest RB is CEO at Perspectum Ltd, CF is employed by Perspectum Ltd. MC is a consultant without fee at Perspetum Ltd. LC, MP, DPB, FL, GM, AP, CG, MS, ES, CM, DI, DD, AN, MGV, LA, RC, SS, SF and PI have nothing to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gastric cancer (GC) is a relevant public health issue as its incidence and mortality rates are growing worldwide. There are recognized carcinogen agents, such as obesity, tobacco, meat, alcohol consumption and some dietary protective factors. Strategies of early diagnosis through population-based surveillance programs have been demonstrated to be effective in lowering the morbidity and mortality related to GC in some countries. Indeed, the detection of early lesions is very important in order to offer minimally invasive treatments. Endoscopic resection is the gold standard for lesions with a low risk of lymph node metastasis, whereas surgical mini-invasive approaches can be considered in early lesions when endoscopy is not curative. This review outlines the role of lifestyle and prevention strategies for GC, in order to reduce the patients' risk factors, implement the surveillance of precancerous conditions and, therefore, improve the diagnosis of early lesions. Furthermore, we summarize the available treatments for early gastric cancer.

Autoimmune liver diseases (AiLDs) are rare autoimmune conditions of the liver and the biliary tree with unknown etiology and limited treatment options. AiLDs are inherently characterized by a high degree of complexity, which poses great challenges in understanding their etiopathogenesis, developing novel biomarkers and risk-stratification tools, and, eventually, generating new drugs. Artificial intelligence (AI) is considered one of the best candidates to support researchers and clinicians in making sense of biological complexity. In this review, we offer a primer on AI and machine learning for clinicians, and discuss recent available literature on its applications in medicine and more specifically how it can help to tackle major unmet needs in AiLDs., Competing Interests: Author DV is employed by Rulex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gerussi, Scaravaglio, Cristoferi, Verda, Milani, De Bernardi, Ippolito, Asselta, Invernizzi, Kather and Carbone.)

Background & Aims: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy., Methods: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs)., Results: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA., Conclusions: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Primary biliary cholangitis (PBC) is a complex, chronic disease with a heterogeneous presentation, disease progression, and response to therapy. Several prognostic models based on disease stage and/or treatment response enhance risk stratification and therapeutic management. Recent work on disease modeling proposed early prediction of outcomes at PBC onset, yet this has not been implemented in clinical practice. Although early stratification of patients based on their individual risk of developing end-stage liver disease may prove cost-effective and actually become matter of medical deontology to timely offer the best therapeutic option, given the forthcoming availability of novel, disease-modifying drugs. This review outlines established and novel prognostic systems in PBC and provides some perspectives on the potential role of omics-derived biomarkers in developing reliable risk prediction models and promoting the implementation of personalized medicine in PBC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA). The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor. In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies., Competing Interests: Conflicts of interest Pietro Invernizzi and Sara Massironi are members of the European Reference Network on Hepatological Diseases (ERN RARE LIVER), and they thank AMAF Monza ONLUS and AIRCS for the unrestricted research funding. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Mastocytosis is a rare and heterogeneous disease characterized by various clinical and biological features that affect different prognoses and treatments. The disease is usually divided into 2 principal categories: cutaneous and systemic disease (SM). Clinical features can be related to mast cell (MC) mediator release or pathological MC infiltration. SM is a disease often hard to identify, and the diagnosis is based on clinical, biological, histological, and molecular criteria with different specialists involved in the patient's clinical work-up. Among all manifestations of the disease, gastrointestinal (GI) symptoms are common, being present in 14%-85% of patients, and can significantly impair the quality of life. Here we review the data regarding GI involvement in SM, in terms of clinical presentations, histological and endoscopic features, the pathogenesis of GI symptoms, and their treatment., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflict of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Duodenal gastric metaplasia (DGM) is considered a precancerous lesion. No data are available regarding its possible role as a risk factor for duodenal neuroendocrine neoplasms (dNENs)., Aims: To assess the prevalence of DGM in a cohort of dNENs., Methods: Subgroup analysis of a retrospective study including dNEN patients who underwent surgical resection between 2000 and 2019 and were observed at eight Italian tertiary referral centers., Results: 109 dNEN patients were evaluated. Signs of DGM associated with the presence of dNEN were reported in 14 patients (12.8%). Among these patients, nine (64.4%) had a dNEN of the superior part of the duodenum, one (7.1%) a periampullary lesion, three (21.4%) a dNEN located in the second portion of the duodenum, with a different localization distribution compared to patients without DGM ( p = 0.0332). Ten were G1, three G2, and in one patient the Ki67 was not available. In the group with DGM, six patients (35.7%) were classified at stage I, five (28.6%) at stage II, three (21.4%) at stage III, and no one at stage IV. In the group without DGM, 20 patients (31%) were at stage I, 15 (15%) at stage II, 42 (44%) at stage III, and 19 (20%) at stage IV ( p = 0.0236). At the end of the study, three patients died because of disease progression., Conclusions: our findings might suggest that DGM could represent a feature associated with the occurrence of dNEN, especially for forms of the superior part of the duodenum, which should be kept in mind in the endoscopic follow up of patients with DGM. Interestingly, dNEN inside DGM showed a more favorable staging, with no patients in stage IV. The actual relationship and the clinical relevance of this possible association require further clarification.

Objectives: Early palliative supportive care has been associated with many advantages in patients with advanced cancer. However, this model is underutilised in patients with haematological malignancies. We investigated the presence and described the frequency of quality indicators for palliative care and end-of-life care in a cohort of patients with acute myeloid leukaemia receiving early palliative supportive care., Methods: This is an observational, retrospective study based on 215 patients consecutively enrolled at a haematology early palliative supportive care clinic in Modena, Italy. Comprehensive hospital chart reviews were performed to abstract the presence of well-established quality indicators for palliative care and for aggressiveness of care near the end of life., Results: 131 patients received a full early palliative supportive care intervention. All patients had at least one and 67 (51%) patients had four or more quality indicators for palliative care. Only 2.7% of them received chemotherapy in the last 14 days of life. None underwent intubation or cardiopulmonary resuscitation and was admitted to intensive care unit during the last month of life. Only 4% had either multiple hospitalisations or two or more emergency department access. Approximately half of them died at home or in a hospice. More than 40% did not receive transfusions within 7 days of death. The remaining 84 patients, considered late referrals to palliative care, demonstrated sensibly lower frequencies of the same indicators., Conclusions: Patients with acute myeloid leukaemia receiving early palliative supportive care demonstrated high frequency of quality indicators for palliative care and low rates of treatment aggressiveness at the end of life., Competing Interests: Competing interests: FF: advisory boards for Janssen and Novartis and travel grants from Jazz Pharmaceuticals, outside the submitted work. RM: honoraria from AbbVie, Roche, Janssen and Shire, outside the submitted work. FE: consultancy for AbbVie, Amgen, Janssen, Orsenix and Takeda and grants from Amgen (to his institution), outside the submitted work. EB: grants from Helsinn Healthcare, outside the submitted work. ML: advisory board for AbbVie, Novartis, Gilead Sciences, Jazz Pharmaceuticals, Sanofi, MSD and Daiichi Sankyo and travel grant from Gilead Sciences., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)