Objective Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis—Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. Design Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. Results After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. Conclusions The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. Trial registration number NCT04777812.

Introduction: Duodenoscopes have been widely used for both diagnostic and therapeutic endoscopic retrograde cholangiopancreatography procedures. Numerous outbreaks of duodenoscope-associated infections involving multidrug-resistant bacteria have recently been reported. Plasma activated water (PAW) has been widely considered an effective agent for surface decontamination and is increasingly used for disinfection of medical equipment. The aim of this study was to evaluate whether the duodenoscopes currently on market are suited for the repeated use of PAW and to test the efficacy of PAW for their disinfection. Materials and methods: In order to evaluate the disinfection efficacy and the required time of contact, the duodenoscope samples were contaminated by immersing them in fasted-state simulated intestinal fluid containing Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, prior to PAW exposure. In order to test the duodenoscope polymer compatibility with PAW, a challenge test was conducted by immersing the samples in PAW for 30 minutes daily for 45 consecutive days. Results: Significant reductions in bacterial populations were achieved after 30 minutes of PAW treatment, indicating a high-level disinfection. Atomic force microscopy and scanning electron microscopy were used to demonstrate that repeated PAW treatment of duodenoscope coating polymer samples did not result in significant differences in morphological surface between the treated and untreated samples. Energy-dispersive X-ray spectroscopy analysis also showed no significant differences between the elemental composition of the duodenoscope coating polymer samples before and after repeated PAW treatment. Conclusion: Considering these preliminary results, PAW could be considered as a new alternative for duodenoscope reprocessing.

Primary sclerosing cholangitis is a progressive liver disease characterized by chronic inflammation leading to liver fibrosis and cirrhosis. Even though the exact pathogenesis is still unclear, a combination of autoimmune, environmental, and ischemic factors could explain certain aspects of the disease. The most important diagnostic step is cholangiography, which can be obtained either by endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiography (MRCP as the gold standard), or percutaneous transhepatic cholangiography. It shows multifocal short biliary duct strictures leading to the “beaded” aspect. Cholangiocarcinoma and colorectal adenocarcinoma are the most feared complications in patients with Primary sclerosing cholangitis (PSC). Continuous screening consists of annual clinical, biochemical, and ultrasound assessments in asymptomatic patients and annual colonoscopy in patients with PSC and inflammatory bowel disease. In newly diagnosed patients with PSC, colonoscopy is mandatory and, if negative, then, a repeat colonoscopy should be performed in 3–5 years. The lack of efficient curative medical treatment makes invasive treatments such as liver transplant and endoscopy the mainstream for managing PSC and its complications. Until now, even though only ursodeoxycholic acid has shown a moderate clinical, biochemical, and even histological improvement, it has no significant influence on the risk of cholangiocarcinoma, liver transplant need, or death risk and it is no longer recommended in treating early PSC. Further studies are in progress to establish the effect of molecular-targeted therapies in PSC.

Background and Aims: The fully-covered, lumen apposing metal stents are designed for one step placement, facilitating the direct endoscopic necrosectomy into the walled-off pancreatic necrosis. However, the prediction of the number of necrosectomy sessions in these patients is not known. This study evaluated the association between the proportion of solid necrotic material inside walled-off necrosis, as assessed during the endosonography placement of a lumen apposing metal stent, and the number of necrosectomies subsequently required. Methods: Patients from three tertiary medical centers with symptomatic walled off pancreatic necrosis (pain, infection, gastric/biliary obstruction) at more than 4 weeks after onset of acute pancreatitis were retrospectively analysed. Proportion of solid necrotic debris was estimated during endosonography procedure of lumen apposing metal stents placement. Necrosectomy was performed when obstruction or inflammation occurred subsequently. Lumen apposing metal stents were removed after clearance of necrotic content. Results: In 46 patients with successful lumen apposing metal stents placement, necrosectomy was performed in 39 patients (72.78%). Performance of 3 or more necrosectomies was significantly associated with more than 50% pancreatic necrosis (p=0.032), but not with walled-off pancreatic necrosis size or location. Necrotic infection during lumen apposing metal stents stenting was associated with hypoalbuminemia, but not with necrosectomy requirement. Clinical success after a median follow-up of 13.37 months was 87%. Conclusions: Walled-off pancreatic necrosis with more than 50% solid necrotic content were associated with more necrosectomy procedures, requiering longer endoscopy time, intravenous sedations, and higher costs.

Objective: Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA. Design: Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more), patients with hereditary syndromes and those undergoing pancreatoduodenectomy were excluded. All remaining cases as well as a subgroup of them, after propensity-score matching (nearest-neighbour-method) based on age, gender, anthropometrics, comorbidities, size and histological subtype, were analysed. The median follow-up was 21 months (IQR 10–47) after the primary intervention. Primary outcomes were rates of complete resection (R0) and complications. Groups were compared by Fisher’s exact or χ ² test, Mann-Whitney-U-test and log-rank test for survival. Results: Of 1673 patients in the database, 1422 underwent EP and 251 TSA. Of them, 23.2% were excluded for missing or inconclusive data and 19.8% of patients for prior interventions or hereditary syndromes. Final histology showed in 24.2% of EP and 14.8% of TSA patients a histology other than adenoma or adenocarcinoma while advanced cancers were recorded in 10.9% of EP and 36.6% of TSA patients. Finally, 569 EP and 63 TSA were included in the overall analysis, with a higher rate of more advanced cases and higher R0 resection rates in the TSA groups (90.5% vs 73.1%; p<0.01), with additional ablation in the EP group in 14.4%. Severe adverse event rates were 3.2% (TSA) vs 1.9% (EP). Recurrence after histological R0 resection was 16% (EP) vs 3.2% (TSA; p=0.01), and additional therapy for R1 resection was applied in 67% of the 159 cases. Propensity-score-based matching identified 62 pairs of EP/TSA patients with comparable baseline patient and lesion characteristics. The initial R0-rate was 72.6% (EP) compared with 90.3% (TSA, p=0.02) with recurrences found in 8% (EP) vs 3.2% (TSA; p=0.07); reinterventions were more frequent in the EP group. Overall survival was comparable. Conclusions: The rate of patients with poor indications due to non-neoplastic disease or advanced cancer is still high for both EP and TSA; multiple retreatments were necessary for EP. Although EP can be considered an appropriate primary therapy for certain ampullary adenomas, case selection for both therapies (especially with regard to the best step-up approach) should be studied further.

Background: Colorectal cancer affects a large number of patients worldwide, with numerous factors being involved in its etiopathogenesis and chronic inflammation playing an essential role in tumor development. In this study, we analyzed and compared several markers of inflammation that are relatively easy to obtain for a rapid and accurate diagnosis and prognosis. Methods: This study included 219 patients diagnosed with colorectal cancer, analyzing the inflammation scores derived from their blood cells and inflammatory circulating proteins. These inflammatory markers are neutrophil-to-lymphocyte ratio—NLR; platelet-to-lymphocyte ratio—PLR; lymphocyte-to-monocyte ratio—LMR; systemic immune inflammation index—SII; systemic inflammatory response index—SIRI; aggregate index of systemic inflammation—AISI; derived neutrophil-to-lymphocyte ratio—dNLR; C-reactive protein-to-albumin ratio—CAR; and fibrinogen-to-albumin ratio—FAR. In the analysis of patients with colorectal cancer, we have also introduced two new recently developed inflammatory markers: the cumulative inflammatory index (IIC) and the ratio between the mean corpuscular volume and lymphocytes (MCVL). This study aimed to correlate the inflammatory markers’ levels with the colorectal cancer diagnostic stage, the tumor and clinical characteristics of the colorectal cancer patients, and 36 months’ survival time and to evaluate the diagnostic and prognostic capacity and accuracy of these inflammatory markers in this type of cancer. Results: We showed that the levels of the analyzed inflammation markers correlate with the TNM stage, the tumor pathological differentiation grade, the age and gender of the patients, and overall survival, with their increased levels being associated with a lower survival rate. Conclusions: The analyzed markers, which are easy to perform right from the patient’s admission, can be helpful both in diagnosis and, mostly, in prognosis, sustaining the role of inflammation in cancer. By comparing them, we showed which one can be useful for increased sensitivity and specificity in the diagnosis and prognosis of colorectal cancer patients.