BACKGROUND:Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN) can be difficult to treat using traditional endoscopic resection methods. This study evaluated the outcomes of endoscopic submucosal dissection (ESD) in patients with IBD and HR-CANs. METHODS:This retrospective multicenter study consecutively included patients with IBD who were referred to expert Italian endoscopy centers for ESD or hybrid ESD (hESD) of HR-CANs. The main outcomes were rates of en bloc, R0, and curative resections, adverse events, local recurrence, metachronous lesions, and post-resection surgery. Kaplan-Meier method was used to analyze survival rates. Risk factors associated with the main outcomes were investigated by univariable analysis. RESULTS:91 patients with colonic IBD (disease duration 15.3 [SD 8.7] years, 82.4 % with ulcerative colitis) with 96 HR-CANs (mean size 34.8 [SD 16.2] mm, 53.1 % high grade dysplasia/adenocarcinoma) were included. ESD and hESD were performed in 82.3 % and 17.7 %, respectively. En bloc, R0, and curative resections were achieved in 95.8 % (95 %CI 89.6-98.8), 85.4 % (95 %CI 76.7-91.7), and 83.3 % (95 %CI 74.3-90.1). Adverse events occurred in 12.5 % (95 %CI 6.6-20.8), which were all conservatively managed. After a mean follow-up of 23.4 (SD 16.1) months, local recurrence and metachronous lesions each occurred in 3.1 %. Post-resection surgery was required in 11.5 %. CONCLUSIONS:ESD of HR-CANs showed favorable outcomes on the medium- and long-term course in patients with IBD.

Background and aim Endoscopic mucosal resection (EMR) of superficial nonampullary duodenal epithelial tumors (SNADETs) is challenging, and to date, only a few studies assessed the clinical outcomes of EMR in the duodenum. The aim of this study was to evaluate the efficacy and safety of EMR for the treatment of SNADETs >10 mm. Patients and methods This is a single-center retrospective study reporting data from a cohort of consecutive patients undergoing EMR of large (>1 cm) SNADETs between January 2017 and December 2021. Results A total of 81 patients with 83 lesions underwent EMR (70 conventional EMR, 13 underwater EMR). The median size was 20 mm (range: 10–60 mm). The mean procedure time was 45 ± 30 min, and the en-bloc resection rate was 47%. In all patients, SNADETs were successfully removed (i.e. technical success). Delayed bleeding occurred in 5 (6%) of EMRs. One delayed perforation occurred, which was managed surgically. Recurrence rate was 20% with a median follow-up period of 20.5 months. Recurrence was detected at the first endoscopic follow-up in 88% of cases, and all recurrences were successfully treated endoscopically. Lesion size ( P = 0.04), previous endoscopic resection ( P = 0.05), and piecemeal resection ( P = 0.05) were independent risk factors of local recurrence after EMR on multivariate-adjusted analysis. Conclusion Large duodenal adenomas can be effectively managed by EMR. However, duodenal EMR of large lesions carries a significant risk of early recurrence, with a nonnegligible risk of adverse events. Lesion dimension, piecemeal resection, and previous endoscopic resection were associated with a higher recurrence rate. Close endoscopic follow-up is recommended given the high incidence of early recurrence, which can be successfully treated endoscopically.

Aims Endoscopic submucosal dissection (ESD) constitutes the standard of care for local excision and staging of early rectal cancer. Patients with deep submucosal invasion into the mid-lower third of the submucosa (pT1b-SM2,3) or the muscle layer (pT2), are currently diagnosed with a non-curative resection and additional surgery protrudes as the most suitable approach according to the present guidelines. This study aimed to evaluate the efficacy of adjuvant radiotherapy and/or chemotherapy following endoscopic resection for reducing recurrence after local resection in patients diagnosed with deeply infiltrative rectal polyps unwilling or unsuitable for additional surgical resection.

IntroductionColorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC.Areas coveredThe aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening.Expert opinionWe suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programs and support research project to further increase the accuracy of CRC screening tests and strategies.

Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in the last two decades. The incidence of pancreatic cancer is increasing, and it continues to be associated with high mortality and morbidity rates. The difficulty of early diagnosis (the lack of specific symptoms and biomarkers at early stages), the aggressiveness of the disease, and its resistance to systemic therapies are the main factors for the poor prognosis of pancreatic cancer. The only curative treatment for pancreatic cancer is surgery, but the vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. Pancreatic surgery is among the most challenging surgical procedures, but recent improvements in surgical techniques, careful patient selection, and the availability of minimally invasive techniques (e.g., robotic surgery) have dramatically reduced the morbidity and mortality associated with pancreatic surgery. Patients who are not candidates for surgery may benefit from locoregional and systemic therapy. In some cases (e.g., patients for whom marginal resection is feasible), systemic therapy may be considered a bridge to surgery to allow downstaging of the cancer; in other cases (e.g., metastatic disease), systemic therapy is considered the standard approach with the goal of prolonging patient survival. The complexity of patients with pancreatic cancer requires a personalized and multidisciplinary approach to choose the best treatment for each clinical situation. The aim of this article is to provide a literature review of the available treatments for the different stages of pancreatic cancer.

Background & Aims: Common precursors for the liver, biliary tree, and pancreas exist at an early stage of development in the definitive endoderm forming the foregut. We have identified and characterised endodermal stem/progenitor cells with regenerative potential persisting in the adult human duodenum. Methods: Human duodena were obtained from organ donors, and duodenal submucosal gland cells were isolated after removal of the mucosa layer. Cells were cultured on plastic or as organoids and were transplanted into severe combined immunodeficient (SCID) mouse livers. Results: In situ studies of submucosal glands in the human duodenum revealed cells expressing stem/progenitor cell markers that had unique phenotypic traits distinguishable from intestinal crypt cells. Genetic signature studies indicated that the cells are closer to biliary tree stem cells and to definitive endodermal cells than to adult hepatocytes, supporting the interpretation that they are endodermal stem/progenitor cells. In vitro, human duodenal submucosal gland cells demonstrated clonal growth, capability to form organoids, and ability to acquire functional hepatocyte traits. In vivo, transplanted cells engrafted into the livers of immunocompromised mice and differentiated to mature liver cells. In an experimental model of fatty liver, human duodenal submucosal gland cells were able to rescue hosts from liver damage by supporting repopulation and regeneration of the liver. Conclusions: A cell population with clonal growth and organoid formation capability, which has liver differentiation potency in vitro and in vivo in murine experimental models, is present within adult duodenal submucosal glands. These cells can be isolated, do not require reprogramming, and thus could potentially represent a novel cell source for regenerative medicine of the liver. (c) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients' responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota-including the gut, pancreatic, and oral microbiota-in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease.

Background and aims Endoscopic treatment of recurrent/residual colonic lesions on scars is a challenging procedure. In this setting, endoscopic submucosal dissection (ESD) is considered the first choice, despite a significant rate of complications. Endoscopic full-thickness resection (eFTR) has been shown to be well-tolerated and effective for these lesions. The aim of this study is to conduct a comparison of outcomes for resection of such lesions between ESD and eFTR in an Italian and a Japanese referral center. Methods From January 2018 to July 2020, we retrospectively enrolled patients with residual/recurrent colonic lesions, 20 treated by eFTR in Italy and 43 treated by ESD in Japan. The primary outcome was to compare the two techniques in terms of en-bloc and R0-resection rates, whereas complications, time of procedure, and outcomes at 3-month follow-up were evaluated as secondary outcomes. Results R0 resection rate was not significantly different between the two groups [18/20 (90%) and 41/43 (95%); P = 0.66]. En-bloc resection was 100% in both groups. No significant difference was found in the procedure time (54 min vs. 61 min; P = 0.9). There was a higher perforation rate in the ESD group [11/43 (26%) vs. 0/20 (0%); P = 0.01]. At the 3-month follow-up, two lesions relapsed in the eFTR cohort and none in the ESD cohort ( P = 0.1). Conclusion eFTR is a safer, as effective and equally time-consuming technique compared with ESD for the treatment of residual/recurrent colonic lesions on scars and could become an alternative therapeutic option for such lesions.

Background and aims: To date, western data on colorectal ESD are limited. This study aimed to assess the efficacy and safety of rectal ESD for superficial lesions >= 8 cm.Methods: A total of 138 superficial rectal neoplasms treated by ESD were allocated in two groups: 25 in the "giant" ESD group and 113 in the control group.Results: En bloc resection was achieved in 96% of cases in both groups. En bloc R0 resection rate was similar between the "giant" ESD group and the control group (84% vs 86%; p: 0.5) and curative resection was higher in the control group (81%) than in "giant" ESD group (68%) without reaching statistical sig-nificance (p: 0.2). Dissection time was significantly longer in the "giant" ESD group (251 vs 108 min; p < 0.001), however, dissection speed was significantly higher (0.35 vs 0.17 cm2/min; p: 0.02).). Post-ESD stenosis was observed in 2 patients from the "giant" ESD group (8% vs 0% of control group, p: 0.03). No significant differences were found in delayed bleeding, perforation, local recurrences, and need for additional surgery.Conclusions: ESD for superficial rectal tumors >= 8 cm is a feasible, safe, and effective therapeutic option.(c) 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

We read with great interest the recently published review by Radaelli et al. [ [1] Radaelli F. Fuccio L. Paggi S. et al. What gastroenterologists should know about direct oral anticoagulants. Dig Liver Dis. 2020; https://doi.org/10.1016/j.dld.2020.04.032.S1590-8658(20)30187-0 Crossref Google Scholar ] concerning the use of Direct Oral Anticoagulants (DOAC) in gastroenterological patients emphasizing among the risk factors for gastrointestinal (GI) bleeding an age ≥75 years, renal impairment, history of GI bleeding, concomitant use of antiaggregants and non-steroidal anti-inflammatory drugs (NSAIDs). A very recent systematic review and meta-analysis cited in the above-mentioned paper by Radaelli et al., concluded that there was no significant difference of major GI bleeding between different DOACs compared with conventional treatment [ [2] Gu Z.C. Wei A.H. Zhang C. et al. Risk of major gastrointestinal bleeding with new vs conventional oral anticoagulants: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020; 18: 792-799 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar ]. What gastroenterologists should know about direct oral anticoagulantsDigestive and Liver DiseaseVol. 52Issue 10PreviewDirect oral anticoagulants are being increasingly used in patients with non-valvular atrial fibrillation and venous thromboembolism, due to their improved efficacy/ safety ratio, a predictable anticoagulant effect without need for routine coagulation monitoring, and fewer food and drug interactions compared with vitamin K antagonists. Gastrointestinal bleeding remains a serious complication, whose management is challenging for gastroenterologists due to the lack of a standardized clinical approach. Full-Text PDF

Cell adhesion is essential for survival, it plays important roles in physiological cell functions, and it is an innovative target in regenerative medicine. Among the molecular interactions and the pathways triggered during cell adhesion, the binding of cluster of differentiation 44 (CD44), a cell-surface glycoprotein involved in cell-cell interactions, to hyaluronic acid (HA), a major component of the extracellular matrix, is a crucial step. Cell therapy has emerged as a promising treatment for advanced liver diseases; however, so far, it has led to low cell engraftment and limited cell repopulation of the target tissue. Currently, different strategies are under investigation to improve cell grafting in the liver, including the use of organic and inorganic biomatrices that mimic the microenvironment of the extracellular matrix. Hyaluronans, major components of stem cell niches, are attractive candidates for coating stem cells since they improve viability, proliferation, and engraftment in damaged livers. In this review, we will discuss the new strategies that have been adopted to improve cell grafting and track cells after transplantation.

During foetal life, the liver plays the important roles of connection and transient hematopoietic function. Foetal liver cells develop in an environment called a hematopoietic stem cell niche composed of several cell types, where stem cells can proliferate and give rise to mature blood cells. Embryologically, at about the third week of gestation, the liver appears, and it grows rapidly from the fifth to 10th week under WNT/β-Catenin signaling pathway stimulation, which induces hepatic progenitor cells proliferation and differentiation into hepatocytes. Development of new strategies and identification of new cell sources should represent the main aim in liver regenerative medicine and cell therapy. Cells isolated from organs with endodermal origin, like the liver, bile ducts, and pancreas, could be preferable cell sources. Furthermore, stem cells isolated from these organs could be more susceptible to differentiate into mature liver cells after transplantation with respect to stem cells isolated from organs or tissues with a different embryological origin. The foetal liver possesses unique features given the co-existence of cells having endodermal and mesenchymal origin, and it could be highly available source candidate for regenerative medicine in both the liver and pancreas. Taking into account these advantages, the foetal liver can be the highest potential and available cell source for cell therapy regarding liver diseases and diabetes.