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Background Recently, comparative trials among biologics in ulcerative colitis (UC) provided conflicting results on their reciprocal superiority or equivalence. Therefore, in patients naive to biologics, the first-choice biological drug is uncertain. Methods In a retrospective, real-life, multicentre inception cohort study involving 11 Italian IBD tertiary centres, all consecutive patients, naive to biologics, treated with adalimumab (ADA), infliximab biosimilar (CTP-13), golimumab (GOL) or vedolizumab (VDZ) after their postmarketing approval (2014–2018) for moderate–severe active UC, were followed up for 1 year or until relapse. All drugs were compared with each other and to naive patients treated with IFX-originator (IFX-O, Remicade) in 2013–2014 as a reference group. A propensity score analysis was performed. The primary endpoint was the 1 year relapse-free, optimisation-free, steroid-free remission, defined as Mayo score ≤2, with bleeding subscore = 0, no relapse after first clinical remission and no optimisation with dose intensification or steroids courses. Multiple further secondary endpoints were analysed (Table 1). Results Two hundred ninety-six naive patients (ADA = 56, CTP-13 = 73, GOL = 60, VDZ = 34, IFX-O = 73) were included. The primary end-point was achieved in similar percentages in all groups, irrespective of optimisation. IFX-O and ADA had similar rates of clinical remission achieved once during the follow-up but higher rates than GOL and VDZ. The 1-year relapse rate, however, was lower with VDZ than ADA, GOL and IFX-O. Treatment failure for primary/secondary no response was higher with GOL than IFX-O and ADA. Treatment failures for intolerance were similar among all drugs. CTP-13 performed differently than the originator for some secondary end-points. Conclusion Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year in patients naive to these drugs. IFX originator and ADA appear more effective in the induction phase, while patients responders to VDZ had more prolonged clinical remission. Some differences on secondary questionable outcomes between IFX biosimilar and originator have been observed.

Background Until 2014, infliximab originator (Remicade, IFX-O) was the only biological treatment approved in Italy for ulcerative colitis (UC), followed by the sequential approval of adalimumab (ADA), infliximab biosimilar (CTP-13), golimumab (GOL) and vedolizumab (VDZ). Recently, comparative trials among these drugs provided conflicting results on their reciprocal superiority or equivalence. Methods In a retrospective, real-life, multicenter inception cohort study involving 11 Italian IBD tertiary centres, all consecutive patients with moderate-to-severe active UC, treated with ADA, CTP-13, GOL or VDZ after their post-marketing approval (2014–2018) were followed-up for 1 year or until relapse. All drugs were compared with each other and to patients treated with Remicade in 2013–2014 (reference group). The 80% power calculation of the study required at least 75 patients in each arm. A propensity score analysis was performed. The primary endpoint was the 1 year relapse-free, optimisation-free, steroid-free remission, defined as Mayo partial score ≤2, with bleeding subscore = 0, no relapse after first clinical remission and no optimisation with dose intensification or steroids courses. Multiple further secondary endpoints were analysed (Table 1). Results 492 patients (ADA=90, CTP-13=105, GOL=79, VDZ=142, IFX-O=76) were included. Overall, 65% achieved clinical remission once during the follow-up, with IFX-O performing better than GOL and VDZ. The relapse rate was 24%, with the lowest rates with VDZ. The primary end-point was achieved in similar percentages in all groups, except for lower rates with GOL than IFX-O. IFX-O performed better than each other drug for other clinical outcomes (Table 1). Discontinuation for intolerance was similar among the drugs, but CTP-13 had more frequent adverse events (mainly infusion reactions) than ADA, VDZ and IFX-O. Conclusion Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year, except for GOL vs. IFX originator. IFX-O appears more effective in multiple questionable clinical outcomes. IFX biosimilar had more adverse events than the other drugs. IFX originator should be used as the reference drug in head to head, controlled, comparison trials for current and future biologics in UC.

Background Magnetic resonance cholangio-pancreatography (MRCP), endoscopic ultrasonography (EUS), and endoscopic cholangio-pancreatography (ERCP) are the most frequently employed second-step procedures to detect biliary and pancreatic abnormalities in patients with acute recurrent pancreatitis (ARP) of unknown aetiology. MRCP and EUS both give a better view of the bilio-pancreatic ductal system after secretin stimulation (MRCP-S, EUS-S). EUS also serves to identify changes in the pancreatic parenchyma consistent with chronic pancreatitis, at an early stage. However, no studies have compared MRCP-S, EUS-S, and ERCP in the diagnosis of recurrent pancreatitis. Aim To prospectively compare the diagnostic yield of MRCP-S, EUS-S, and ERCP in the evaluation of patients with acute recurrent pancreatitis with non-dilated ducts, of unknown aetiology. Methods Forty-four consecutive patients with ARP were prospectively scheduled to undergo MRCP-S, EUS-S and ERCP, in accordance with a standard protocol approved by the institutional review board. Diagnoses such as biliary microlithiasis, congenital variants of the pancreatic ducts, chronic pancreatitis and sphincter of Oddi dysfunction were compared between the three procedures. The diagnosis of chronic pancreatitis was established according to ductal morphology by MRCP-S and ERCP, ductal and parenchymal morphology by EUS-S. Results The three procedures combined achieved a diagnosis that could have explained the recurrence of pancreatitis in 28/44 patients (63.6%). EUS-S recognized ductal and/or parenchymal abnormalities with the highest frequency (35/44 patients, 79.5%). Both MRCP-S and EUS-S were superior to ERCP for detecting pancreatic ductal abnormalities. EUS-S showed up pancreatic parenchymal changes in more than half the cases. Both EUS and MRCP secretin kinetics were concordant in identifying two cases with sphincter of Oddi dysfunction. Conclusions The diagnostic yield of EUS-S in recurrent pancreatitis with non-dilated ducts and unknown aetiology was 13.6% and 16.7% higher than MRCP-S and ERCP respectively (although not significant), which both gave substantially similar diagnostic yields. In no case did ERCP alone find a diagnosis missed by the other two procedures. MRCP-S and EUS-S should both be used in the diagnostic work-up of idiopathic recurrent pancreatitis as complementary, first-line, techniques, instead of ERCP.

Background and study aims Acute pancreatitis is still the most common complication after endoscopic sphincterotomy (ES) and cholangiopancreatography (ERCP). The aim of this study was to detect the time when the peak of serum amylase was predictive for postprocedure pancreatitis or long-lasting severe hyperamylasemia, in order to plan the follow-up of patients. Methods Serum amylase activity was measured in a prospective series of 409 consecutive patients after ES, immediately before ES and two, four, eight and 24 hours thereafter; the two, four and eight-hour data were compared with those at 24 hours and with the outcome. Evaluation was done separately for the 198 cases with pancreatic duct opacification and for the 202 cases at high risk for postprocedure pancreatitis. Results Twenty-four hours after ES, amylase was still more than five times the upper normal limit in 26 patients, associated with pancreatic-like pain in 19 of them (mild/moderate pancreatitis) and asymptomatic in the remaining seven (long-lasting severe hyperamylasemia). There was a significant difference at all sampling times between the 26 patients with 24-hour severe hyperamylasemia and those with the lower level. Although the sensitivity of amylase measurement in detecting pancreatitis was highest at eight hours, in practice the four-hour assessment appears a reliable predictor. Almost all patients with serum amylase levels more than five times the upper normal limit at four, eight and 24 hours had had pancreatic duct opacification. In contrast, patient-related risk factors for postprocedure pancreatitis did not play a significant role in the present series. Conclusions Serum amylase assessment four hours after ES is a reliable, cost-effective follow-up and minimizes the likelihood of underestimating the risk of post-procedure pancreatic reaction. It should be recommended particularly in out-patients and when pancreatic duct opacification has occurred.

Background and aim: Pancreatic NeuroEndocrine Tumors (P-NETs) are a heterogeneous group of neoplasms with highly variable clinical behavior.In the attempt to assess a better prognostic description, the European Neuroendocrine Tumors Society (ENETS) proposed a new grading and TNM-based staging system. Aims of this study were to compare pre-operative and postoperative Staging and Grading in P-NETs and their prognostic significance; to determine if a new cut-off value of Ki-67 proliferative index for P-NETs Grading can improve the accuracy of prognostic stratification. Material and methods: Our retrospective study is composed of 285 patients with P-NETs observed at San Raffaele Scientific Institute from 1988 to 2012. Out of these, 90 and 42, respectively, were classified according to a new presurgical classification, composed of pre-operative Staging (CT, MRI, EUS) and Grading (EUS-guided FNA and cytological Ki-67 evaluation).Comparison between pre and post-operative models (Pre-Stage vs. Stage e Pre-Grade vs. Grade) was possible for 88 and 33 neoplasms, respectively. Ki-67 proliferative index was evaluated through immunocytochemical (Pre-Grade) and immunohistochemical (Grade) analyses. Agreement between pre-operative and post-operative models was performed through k-statistics (Cohen). A p-value

56 patients with large CBD or intrahepatic stones underwent endoscopic and/or percutaneous treatment followed by extracorporeal shock wave lithotripsy. Percutaneous access to the biliary tract was chosen when an endoscopic approach was not possible (hepaticojejunostomy in 5 patients, 1 juxtapapillary diverticulum and I inflammatory bile duct stricture). Visualization of stones was achieved radiologically in 32 patients and by ultrasound in 24. The procedure was successful in 47 of 56 treated patients (83.9%). Clearance of the biliary tract was obtained in 25 cases (53%), whereas in 22 cases (47%) complete clearing of biliary tract was obtained only after endoscopic extraction of fragments (17 cases) or percutaneous (5 cases). The median number of shock waves in each session was 1725 (range 300–3166), which were applied during one (n=30), two (n=22) or three sessions (n=4). The only complications were 1 case of symptomatic hyperamylasemia and 3 cases of macrohematuria. In conclusion, extracorporeal lithotripsy combined with endoscopic and/or percutaneous treatment is a real alternative to surgery for difficult stones.

Background Type 1 sphincter of Oddi dysfunction is a clinical entity characterised by biliary-type pain, elevated liver biochemical tests, and common bile duct dilation. Sphincter fibrosis is a common finding in this type of dysfunction and may require in some cases a differential diagnosis with a malignant intra-papillary disease. Optical coherence tomography permits high-resolution, real-time imaging of the sphincter of Oddi microstructure by a probe inserted into the common bile duct through an ERCP catheter. No data exist on the evaluation of sphincter of Oddi fibrosis by optical coherence tomography during ERCP in vivo. Objective To assess the feasibility of optical coherence tomography investigation of the sphincter of Oddi structure and assess its potential for diagnosing type 1 sphincter of Oddi dysfunction. Patients Ten consecutive patients, five with biliary-type 1 sphincter of Oddi dysfunction and five with pancreatic head/mid-body adenocarcinoma not involving the papillary region, who underwent both endoscopic ultrasound and therapeutic ERCP, were investigated by optical coherence tomography immediately before biliary sphincterotomy or stenting. Results In all sphincter of Oddi dysfunction patients optical coherence tomography recognised a hyper-reflective intermediate, fibro-muscular layer, significantly thicker than in patients with non-pathological sphincter of Oddi (p Conclusions Optical coherence tomography imaging recognised an increased thickness and reflectance of the fibro-muscular layer of the sphincter of Oddi, very likely determined by fibrosis, and was not time-consuming; it can be safely used during ERCP to confirm the diagnosis in difficult cases. Its use in clinical practice has one important limitation since it requires magnification in the post-procedure computer analysis to obtain images useful for diagnosis.

BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P > 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.

Coeliac disease (CD) is a common condition with many atypical manifestations and an estimated worldwide prevalence of 1 in 266.1 It often goes unrecognised because characteristic histopathological abnormalities must be found to confirm the diagnosis. Endoscopic signs of CD are described in the literature but cannot be relied upon for detection of the disease because their sensitivity and specificity are not high. To investigate CD in every patient undergoing oesophagogastroduodenoscopy (OGD) for dyspeptic symptoms is not realistic, especially if we consider the significant costs of histological handling. Therefore, a way of detecting CD is selection of patients in which biopsies of the duodenal mucosa must be performed. A useful new medical technique, optical coherence tomography (OCT), that combines the principles of ultrasound and infrared backscattering light, …

Background Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures. Methods By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience. Results Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe. Conclusions Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.

BACKGROUND AND STUDY AIM The identification of factors which increase the risk of acute pancreatitis, the most common and most severe complication of endoscopic retrograde cholangiopancreatography (ERCP), is of considerable importance. However, in four large prospective studies, the reported incidence of identified risk factors for post-ERCP pancreatitis was found to be variable. The aim of this study was to identify the most important risk factors for post-ERCP pancreatitis. MATERIAL AND METHODS We performed a meta-analysis of 15 prospective clinical studies, selected out of 52 reviewed articles, in which risk factors for pancreatitis were identified. Of the 14 risk factors identified, five were patient characteristics and nine were related to the endoscopic technique. RESULTS When patient-related risk factors were analysed, the relative risk for suspected sphincter of Oddi dysfunction was 4.09 (95 % CI 3.37 to 4.96; P < 0.001); for female gender, 2.23 (95 % CI 1.75 to 2.84, P < 0.001); and for previous pancreatitis, 2.46 (95 % CI 1.93 to 3.12, P < 0.001). Two endoscopy-related factors were confirmed: for precut sphincterotomy the relative risk was 2.71 (95 % CI 2.02 to 3.63, P < 0.001); for pancreatic injection the relative risk was 2.2 (95 % CI 1.6 to 3.01, P < 0.001). CONCLUSIONS This meta-analysis provides a clear basis for planning pharmacological studies or studies of new endoscopic techniques in patients at high risk of developing post-ERCP pancreatitis. Knowing which patients are most at risk may also make it easier to decide who should be considered unsuitable for same-day discharge.

ilatation (with Savary); now the patient is in remission. Two patients (3–4 ears old) have no more symptoms, the EGD is normal, but they are still on ietary treatment. The last two patients are still on medical treatment. Conclusions. In patients with eosinophilic oesophagitis the pH-metry is ormal, the anti-acid therapy is useless and the oesophageal biopsy shows high number of eosinophils (>20/HPF). The differential diagnosis is with astro-oesophageal reflux, allergies, eosinophilic gastroenteritis, parasites nfections, gastrointestinal disorders (coeliac and Crohn disease). The surical approach is necessary only in few cases when there are also other athologies. GER is present in 10% of patients with EE.