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Background and aims: Pancreas divisum (PD) is a congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic minor papilla sphincterotomy (MiES) is the most common procedure performed in the management of PD-related ARP. The aim of this study is to perform a meta-analysis estimating the efficacy and the safety of MiES in the management of patients with PD-related ARP. Methods: A research was performed in Pubmed, EMBASE and Web of science, the studies were reviewed and selected according to inclusion and exclusion criteria. Evaluation of Heterogeneity and publication bias was performed, and a random effect model was used to estimate the effect size of each study. Results: One hundred and thirteen articles were selected and reviewed, 13 met the inclusion criteria. All the studies were retrospective with a mean follow-up duration of 45.9 months. A total of 323 patients with PD-related ARP treated with MiES were included in the meta-analysis. The overall clinical success rate of MiES (defined as no further episodes of ARP, reduction of episodes of ARP, or improvement in quality of life) was of 77% (95%CI: 72%-81%; p = 0.30). Evaluating only the studies with clinical success rate defined as "no further AP in the follow-up" the clinical success rate was of 69.8% (95%CI: 61.3%-77.2%; p = 0.57), while evaluating the studies with other definitions (reduction of episodes of ARP or improvement in quality of life) the clinical success rate was of 81.2% (95%CI: 75.2%-86.1%; p = 0.45). The common fixed effects model disclosed a 25.5% overall adverse events rate (95%CI: 19.3%-32.8%; p = 0.42): acute pancreatitis in 14.3% (95%CI: 9.7%-20.6%; p = 0.36), bleeding in 5.6% (95%CI: 2.9%-10.4%; p = 0.98), and other adverse events in 5.6% (95%CI: 2.9%-10.4%; p = 0.67). Conclusion: MiES is an effective and relatively safe treatment in the management of PD-related ARP. The retrospective nature of the studies selected is the main

Simple Summary Pancreatic cancer is a devasting disease that has unfortunately proven very difficult to treat. Exploring new therapeutic options and getting an early diagnosis is crucial to improve the outcomes for those affected. Studying the intestinal, pancreatic, and oral microbiota offers exciting perspectives to understand the development of pancreatic cancer better. Particular expressions of the microbiota could help both for early diagnosis and for predicting the response to chemotherapy or immunotherapy. This area of research is very promising; therefore, further studies are needed to increase the available data. 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.

Considering the scientific evidence nowadays available, we suggest that IPFD should be carefully differentiated between pancreatic fat accumulation (an overflow of fat in the pancreas in patients with adipose excess) and fatty replacement (characterized by a change in the cellular identity with an acinar-to-adipocyte transdifferentiation in patients with pancreatic damage, such as AP). Different from the conclusions of the authors of this study, we believe that fatty replacement is not the “first hit” predisposing to pancreatic disease, but the “second hit” driving to pancreatic meta-inflammation and chronic damage (Figure 1).

The nutritional management of acute pancreatitis (AP) patients has widely changed over time. The "pancreatic rest" was the cornerstone of the old paradigm, and nutritional support was not even included in AP management. Traditional management of AP was based on intestinal rest, with or without complete parenteral feeding. Recently, evidence-based data underlined the superiority of early oral or enteral feeding with significantly decreased multiple-organ failure, systemic infections, surgery need, and mortality rate. Despite the current recommendations, experts still debate the best route for enteral nutritional support and the best enteral formula. The aim of this work is to collect and analyze evidence over the nutritional aspects of AP management to investigate its impact. Moreover, the role of immunonutrition and probiotics in modulating inflammatory response and gut dysbiosis during AP was extensively studied. However, we have no significant data for their use in clinical practice. This is the first work to move beyond the mere opposition between the old and the new paradigm, including an analysis of several topics still under debate in order to provide a comprehensive overview of nutritional management of AP.

We read with deep interest the position paper from the Italian Association of Hospital Gastroenterologists and Digestive Endoscopists (AIGO) reviewing the environmental impact of gastroenterology and digestive endoscopy. Interestingly the position paper provides information on the carbon footprint of gastroenterology and particularly digestive endoscopy. Impressively, gastroenterology is considered the third largest contributor to waste production in healthcare. ERCP accounts only for the 8% of procedures performed, it accounts for more than 30% of waste generated. This result can be explained because ERCP is frequently performed under general anesthesia generating therefore more waste, and because during ERCP a large number of disposable devices (guidewires, cannulotomes, balloons, baskets etc.) is used if compared with other endoscopic procedures.

Complete hypopharyngeal stenosis is rare and challenging to treat. A 72-year-old man underwent total laryngectomy with bilateral radical neck dissection, total thyroidectomy, and pectoralis major myocutaneous flap reconstruction to treat laryngeal cancer. Following adjuvant radiotherapy, the patient developed an hypopharyngeal stenosis. This was initially treated with endoscopic dilations. However, after 3 years, stricture recurrence led to complete obstruction of the hypopharyngeal lumen that required placement of a percutaneous endoscopic gastrostomy tube for nutrition. After failure of endoscopic ultrasound-guided recanalization, an endoscopic magnetic compression anastomosis was attempted

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that might lead to severe adverse events. Post-ERCP pancreatitis (PEP) is the most common post-procedural complication, which is related to significant mortality and increasing healthcare costs. Up to now, the prevalent approach to prevent PEP consisted of employing pharmacological and technical expedients that have been shown to improve post-ERCP outcomes, such as the administration of rectal nonsteroidal anti-inflammatory drugs, aggressive intravenous hydration, and the placement of a pancreatic stent. However, it has been reported that PEP originates from a more complex interaction of procedural and patient-related factors. Appropriate ERCP training has a pivotal role in PEP prevention strategy, and it is not a chance that a low PEP rate is universally considered one of the most relevant indicators of proficiency in ERCP. Scant data on the acquisition of skills during the ERCP training are currently available, although some efforts have been recently done to shorten the learning curve by way of simulation-based training and demonstrate competency by meeting technical requirements as well as adopting skill evaluation scales. Besides, the identification of adequate indications for ERCP and accurate pre-procedural risk stratification of patients might help to reduce PEP occurrence regardless of the endoscopist’s technical abilities, and generally preserve safety in ERCP. This review aims at delineating current preventive strategies and highlighting novel perspectives for a safer ERCP focusing on the prevention of PEP.

Esophageal perforation is a life-threatening condition burdened by high morbidity and mortality. The esophageal perforation can occur spontaneously (such as Boerhaave syndrome) or can be an iatrogenic complication. The diagnostic approach may be difficult as the clinical presentations is often non-specific. However, a proper and early diagnosis is crucial to reduce the mortality rate. Once the diagnosis is obtained, the therapeutic management differs among the different clinical scenarios. In some cases, a wait and watch approach is preferred, in other cases a more aggressive treatment is required. Although surgery was considered the standard of care, nowadays endoscopy is emerging as the first line treatment in esophageal perforations non-responsive to medical treatments. The endoscopic techniques available are the application of through-the-scope clips (TTSCs), over-the-scope clips, esophageal stents, endoscopic suturing techniques, endoluminal vacuum therapy (EVT), and locoregional application of regenerative medicine. The choice of the specific endoscopic technique depends on the injury length, the perforation site, and the presence of fluid collections. The complexity of the diagnostic and therapeutic approach to esophageal perforation imposes a multidisciplinary approach in order to choose the proper treatment in each singular case. The aim of this study is to assess the role of endoscopy in the management of esophageal injuries and to describe the endoscopic techniques nowadays available.

Patients affected by inflammatory bowel disease (IBD) frequently report impaired quality of sexual life and complain of sexual dysfunctions. Both disease-specific features and psychological factors can be held responsible for these conditions. However, sexuality and all matters relating to sexual health are often wrongfully considered unrelated to IBD and, therefore, overlooked during medical visits. To overcome these difficulties and to best assess patients' perceptions about their sexual health status, the use of patient-reported outcomes (PROs) could represent a valid strategy. In real-world studies, several non-IBD specific questionnaires, exploring different domains of sexuality, have been applied and validated for the IBD population. This review summarizes the available evidence on sexual health among IBD patients and the data supporting the application of PROs to screen the quality of sexual life, as well as the rate and types of sexual dysfunctions, among IBD patients.

Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a "high priority" pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment.

Background: The incidence of ampullary tumors is increasing but data on association with an increased exposure to certain risk factors are scanty. Objective: To investigate risk and protective factors associated with the occurrence of ampullary tumors and whether these factors differ between ampullary tumors of the intestinal and pancreatobiliary subtypes or between adenomas and carcinomas. Methods: The association between a large set of exposome features and ampullary tumors occurrence was investigated in a bi-centric case-control study after ethic committee approval and power calculation. Results: In 223 histologically confirmed patients and 446 controls, previous cholecystectomy (odd ratio [OR] = 2.07; 95% confidence interval [CI] = 1.34-3.20) and proton pump inhibitors use (OR = 1.66; 95% CI = 1.16-2.37) were associated with increased risk of ampullary tumors, aspirin use (OR = 0.57; 95% CI = 0.36-0.90) and light alcohol intake (OR = 0.54; 95% CI = 0.38-0.76) with reduced risk. A previous cholecystectomy was also associated with tumors of intestinal subtype and with both adenomas and carcinomas, and proton pump inhibitors use with adenomas only. Smoking, body mass index, family history of cancers, previous ulcer, diabetes and use of statins, insulin and metformin were not significant factors. Conclusion: This is the first case-control study specifically highlighting factors associated with the occurrence of ampullary tumors. We report factors that are novel and plausible, in keeping with mechanisms described for other gastrointestinal tumors and with potential clinical relevance.

Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.

Acute recurrent pancreatitis (ARP) is a rare manifestation of Intraductal Papillary Mucinous Neoplasms (IPMN) of the pancreas; ARP is a relative indication for pancreatic surgery in the setting of IPMN. Endoscopic pancreatic sphincterotomy (EPS) has been described as a minimal invasive treatment to reduce the episodes of ARP secondary to mucus migration in IPMN.

Background and study aims Endoscopic drainage of benign biliary and pancreatic strictures can be challenging, especially when tightness of the stenosis does not allow passage of mechanical and pneumatic dilation catheters. Electroincision of benign biliopancreatic can be considered in selected cases.Patients and methods Three male patients (mean age 33 years, range 9-60) underwent endoscopic retrograde cholangiopancreatography to drain anastomotic biliary stricture (ABS) following orthotopic liver transplantation (n =2) and pancreatic duct stenosis due to abdominal trauma (n= 1). The biliopancreatic strictures could be passed only with a thin 0.020-inch hydrophilic guidewire. Conventional mechanical and pneumatic dilators failed to pass the strictures due to weakness of the guidewire. Therefore, electrosurgical incision by over-the-wire 6Fr cystotome or needle-knife was attempted using pure cut current.Results The two cases of ABS were approached also by cholangioscopy and the 6Fr cystotome easily passed the strictures, allowing subsequent pneumatic dilatation and insertion of multiple plastic stents. The patient with a pancreatic duct stricture underwent electrosurgical incision using a thin needle knife over-the-wire, resulting in insertion of a 7Fr pancreatic stent. No adverse events occurred; all the patients were discharged within 24 to 48 hours.

Gallbladder cancer is a rare malignancy burdened by poor prognosis with an estimated 5-year survival of 5% to 13% due to late presentation, early infiltration of surrounding tissues, and lack of successful treatments. The only curative approach is surgery; however, more than 50% of cases are unresectable at the time of diagnosis. Endoscopy represents, together with surgery and chemotherapy, an available palliative option in advanced gallbladder cancers not eligible for curative treatments. Cholangitis, jaundice, gastric outlet obstruction, and pain are common complications of advanced gallbladder cancer that may need endoscopic management in order to improve the overall survival and the patients’ quality of life. Endoscopic biliary drainage is frequently performed to manage cholangitis and jaundice. ERCP is generally the preferred technique allowing the placement of a plastic stent or a self-expandable metal stent depending on the singular clinical case. EUS-guided biliary drainage is an available alternative for patients not amenable to ERCP drainage (e.g., altered anatomy). Gastric outlet obstruction is another rare complication of gallbladder malignancy growing in contact with the duodenal wall and causing its compression. Endoscopy is a less invasive alternative to surgery, offering different options such as an intraluminal self-expandable metal stent or EUS-guided gastroenteroanastomosis. Abdominal pain associated with cancer progression is generally managed with medical treatments; however, for incoercible pain, EUS-guided celiac plexus neurolysis has been described as an effective and safe treatment. Locoregional treatments, such as radiofrequency ablation (RFA), photodynamic therapy (PDT), and intraluminal brachytherapy (IBT), have been described in the control of disease progression; however, their role in daily clinical practice has not been established yet. The aim of this study is to perform a review of the literature in order to assess the role of endos

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.

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Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.