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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.

INTRODUCTION:Endoscopic sleeve gastroplasty (ESG) is a relatively novel endoscopic procedure that reduces the gastric lumen with proven less complications and almost same 6 months weight loss compared to laparoscopic sleeve gastroplasty (LSG). To our knowledge there are no trials investigating the role of multidisciplinary evaluation (ME) before and after ESG. The aims of the present study were to evaluate the role of ME prior and after ESG in terms of weight loss outcomes, quality of live improvements and adverse events.METHODS:From May 2016 to April 2019 all patients that underwent ESG were retrospectively evaluated from a prospective database. Included patients had 2° and 3° degree of obesity or 1° with comorbidities. All patients underwent upper GI endoscopy to exclude pathologies. Until September 2017 before ESG only psychiatric evaluation was requested (group 1), while after this date we adopted the guidelines of the Italian Society for Obesity Surgery and all patients were evaluated on a multidisciplinary team composed by gastroenterologist, surgeon, psychiatrist, endocrinologist and dietitian (group 2). We compared this two groups in terms of Excess Weight Loss (%EWL), Total Body Weight Loss (%TBWL) and quality of life improvements, measured with the Bariatric Analysis and Reporting Outcome System (BAROS). ESG was done with the Apollo Overstitch suturing system (Apollo Endosurgery) and a double channel gastroscope Olympus 2TGIF-160 (Olympus Japan) in general anesthesia and with insufflation of CO2. All patients had ambulatory visit t 1, 3, 6 and 12 months after ESG. Statistical analysis was done with chi-square test and < 0.05 value was considered significant. The study was approved by the local Ethical Committee (N° 19211/18).RESULTS:A totally of 89 ESG were performed. Group 1 consisted of 11 patients while Group 2 of 78. Mean procedure time was 51 minutes (range 28-92). Mean number of stitches were 4.7/patient (range 3-8). No procedure related complications were observed. Female were 56 patients; mean age was 45.4 (range 23-73). Mean BMI at inclusion was 41.6 (range 31.6-62.4). Mean %EWL and %TBWL at 12 months was 37.6 and 15.6 respectively (Table 1). Comparing the two groups there was significant (P < 0.05) difference in terms of %EWL, %TBWL and BAROS scale (Table 2) for all periods of follow-up, with better results in group 2.CONCLUSION:ME before and after ESG has a fundamental role in terms of better procedure outcomes for both weight loss and quality of live in obese patients.Table 1.ESG RESULTS ON 89 PATIENTSTable 2.ESG RESULTS ON 89 PATIENTS PRE AND POST MULTIDISCIPLINARY EVALUATION (ME)

Background: Postoperative fluid collections (POFCs) after abdominal surgeries, particularly pancreatic surgeries, are associated with high morbidity and mortality rates and were historically managed with surgical re-exploration and drainage. In particular, postoperative pancreatic fluid collections (PPFCs) are the most common complications after pancreatic surgery resulting from pancreatic leaks. They occur in up to 50% of cases, and approximately 10% of them need to be drained to avoid further sequelae. Endoscopic ultrasonography (EUS)-guided drainage of PPFCs represents the first-line treatment nowadays, but many aspects are still debated. Methods: We describe a retrospective case series of patients from multiple Italian centers who underwent EUS-guided drainage (EUS-D) of POFCs, aiming to provide data on the efficacy and safety of this procedure, supported by a review of the existing literature on this topic. The primary outcomes were technical and clinical success, and the secondary outcomes were the type and rate of adverse events (AEs) and the rate of recurrence. Results: A total of 47 patients were included. The procedure demonstrated a technical success rate of 98% (46/47) and a clinical success rate of 96% (45/47). The rate of AEs was 11% (5/47), represented by bleeding (3/5), stent occlusion (1/5), and buried syndrome (1/5). Conclusions: Management of POFCs has shifted over time towards an endoscopic approach with optimal efficacy and safety.

For many years, cell lines and animal models have been essential to improve our understanding of the basis of cell metabolism, signaling, and genetics. They also provided an essential boost to cancer drug discovery. Nevertheless, these model systems failed to reproduce the tumor heterogeneity and the complex biological interactions between cancer cells and human hosts, making a high priority search for alternative methods that are able to export results from model systems to humans, which has become a major bottleneck in the drug development. The emergent human in vitro 3D cell culture technologies have attracted widespread attention because they seem to have the potential to overcome these limitations. Organoids are unique 3D culture models with the ability to self-organize in contained structures. Their versatility has offered an exceptional window of opportunity to approach human cancers. Pancreatic cancers (PCs) patient-derived-organoids (PDOs) preserve histological, genomic, and molecular features of neoplasms they originate from and therefore retain their heterogeneity. Patient-derived organoids can be established with a high success rate from minimal tissue core specimens acquired with endoscopic-ultrasound-guided techniques and assembled into platforms, representing tens to hundreds of cancers each conserving specific features, expanding the types of patient samples that can be propagated and analyzed in the laboratory. Because of their nature, PDO platforms are multipurpose systems that can be easily adapted in co-culture settings to perform a wide spectrum of studies, ranging from drug discovery to immune response evaluation to tumor-stroma interaction. This possibility to increase the complexity of organoids creating a hybrid culture with non-epithelial cells increases the interest in organoid-based platforms giving a pragmatic way to deeply study biological interactions in vitro . In this view, implementing organoid models in co-clinical trials to compare drug responses may represent the next step toward even more personalized medicine. In the present review, we discuss how PDO platforms are shaping modern-day oncology aiding to unravel the most complex aspects of PC.

EUS-FNB has been introduced in clinical practice as a less invasive diagnostic approach with respect to surgery. We performed a single-center retrospective study on the diagnostic efficacy of EUS-guided FNB, including 171 patients with lymph nodes, splenic, and extranodal lesions that underwent EUS for FNB at our institution. Excluding 12 patients who did not undergo FNB and 25 patients with a previous diagnosis of a solid tumor, we included 134 patients with clinical/radiological suspect of a lymphoproliferative disease, including 20 patients with a previous history of lymphoma. Out of the 134 biopsies, material of diagnostic quality was obtained in 111 procedures (84.3%). Histological examination of the EUS-FNB samples produced an actionable diagnosis in 100 cases (74.6%). Among the patients without an actionable diagnosis, a second, different diagnostic procedure produced a further eight diagnoses of lymphoma. Therefore, the sensitivity of EUS-FNB for diagnosing lymphomas was calculated to be 86.4% (51/59). Assignment of lymphomas to WHO classification subtypes was possible in 47/51 (92%) of the cases. In conclusion, EUS-FNB is an effective procedure for the histological characterization of lesions that are suspected to be lymphoproliferative disease, allowing for an actionable diagnosis in 75% of cases.

Nutritional support is a crucial issue in Acute Pancreatitis (AP) management. Recommendations on nutrition in AP are still not completely translated in the clinical practice. We aimed to compare and evaluate the effects of parenteral nutrition (PN) vs oral/enteral nutrition (EN) on several clinical and economic outcomes in AP. This is a retrospective monocentric study conducted in a tertiary care center for pancreatic diseases. The primary outcomes were length of hospital stay (LOS) and associated costs. The secondary outcomes were the use and cost of antibiotics and fluid therapy, and the complication’s rates. One hundred seventy-one patients were included from January 2015 to January 2018. Patients were 69 (40.4%) in PN group and 102 (59.6%) in EN group. There was a significant reduction in LOS in EN vs PN group in both mild AP (p < 0.0001), and moderate–severe AP (p < 0.005). There was a significant reduction in the total hospitalization costs in EN group vs PN group in both mild AP (p < 0.0001), and moderate–severe AP (p < 0.005). There was a significant reduction in the total costs of antibiotics and pain therapy in EN vs PN group (p < 0.0001 and p = 0.05, respectively). Finally, a significant reduction in the infected peri-pancreatic fluid collections rate (p = 0.04) was observed in EN vs PN group. The use of EN in AP is associated with substantial clinical and economic benefits. Thus, the application of the standard of care in nutrition and following AP guidelines is the best way to cure patients and improve healthcare system costs.

IntroductionEUS-guided drainage by means of Lumen-Apposing Metal Stent (LAMS) represents a minimally invasive treatment of Walled-Off Pancreatic Necrosis (WOPN). In order to achieve a better infection control endoscopic necrosectomy (EN) may be required in a subset of patients, whose early identification may therefore represent a valuable clue in the clinical management of patients with WOPN. MethodsFirstly we retrospectively evaluated 53 patients (“training group”) diagnosed with WOPN (16 females and 37 males, aged 28- 87) admitted to our Institution over the period 2013-2023. In 24 cases (45.3%) EN was required and then performed after LAMS placement.In this group, we identified a predictive Necrosectomy-index (NI), able to provide an “a priori” identification of patients requiring EN, by means of a discriminant-function statistical analysis, taking into consideration only the variables showing a statistical difference (single tail p < 0.10) between the patients requiring EN and the remaining subjects. Thereafter, NI predictive value and clinical reliability (global accuracy and overall statistical significance) were prospectively tested in a separate set of patients with WOPN (“challenge group”), consisting of 53 patients (15 females and 38 males, aged 23- 85).ResultsIn the “training” group, the retrospective analysis of our data allowed to calculate individual NI by means of the simple function: NI = 336 - (PT% * 1.26 + Hb (g/dL) * 29.54 + PLT (kU/mm3) * 0.11 – 48.56 * EUS1) 1EUS subjective rank of collection’s features (0 = fluid; 1 = solid debris; 2 = purulent;3 = necrosis < 50%; 4 = necrosis > 50%; 5 = completely necrotic).The NI provides an early identification of the subset of patients requiring EN after LAMS placement (identified by NI > 0). To increase the predictive ability of the model, the subjects with a NI close to 0 (between 3 and -3) may be considered “undeterminable”, being therefore addressed to EN on the basis of the clinical status. In the prospectively evaluated “challenge” group, NI showed a remarkable overall statistical significance (p < 0.01). The results allow us to confirm NI clinical value (global accuracy of 73.3%, 68.2% predictive value for positivity and 78.3% for negativity) in the early identification of patients further requiring EN. Three patients only (5.7%) showed a NI between 3 and -3, being therefore considered as “undeterminable”. ConclusionsOur data provided a prospective validation of the proposed NI, confirming its reliable intrinsic predictive value. NI may therefore represent a powerful clinical tool in WOPN management, providing an early identification of patients requiring further EN after LAMS placement.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome of patients, only ~20% of them are eligible due to advanced disease at diagnosis. Thus, the development of new therapeutic approaches is a master priority for an improved management of this cancer. The helicase DDX21 was proposed as a prognostic marker in several tumors, including PDAC. Methods: DDX21 expression was evaluated in PDAC samples and cell lines; RNA sequencing and bioinformatics analyses of DDX21-depleted PANC-1 silenced cells; functional analyses of autophagy, cell cycle and proliferation. Results: DDX21 is expressed at higher levels in liver metastasis of PDAC patients. Transcriptomics analyses of DDX21-depleted cells revealed an enrichment in genes involved in autophagy and cell cycle progression. The inactivation of DDX21 by RNA interference enhanced the basal autophagic flux and altered the cell cycle by reducing the rate of G1-S transition. Coherently, PDAC cell proliferation and clonogenic activity was significantly reduced. Conclusions: Our results support the oncogenic role of DDX21 in PDAC and uncover a new role for this helicase in the regulation of basal autophagy.