Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

The impact of a multidisciplinary team approach on the management of focal pancreatic lesions: a single tertiary center experience.

Background: Multidisciplinary team (MDT) meetings aim to optimize patient management. We evaluated the impact of MDT discussions on the management and diagnosis of focal pancreatic lesions in a single tertiary center. Methods: All patients with an initial diagnosis of solid or cystic pancreatic lesion discussed in our institution's MDT meeting on pancreatic diseases between January 1, 2020, and December 31, 2021, were included. The impact of MDT discussion on patient management, defined as a modification of the initially proposed therapeutic plan after MDT discussion, as well as the criteria leading to this modification, were the primary outcomes. Impact on diagnosis was the secondary outcome. Results: A total of 522 patients were included. Of these, 185 (35.4%) and 337 (64.6%) had an initial diagnosis of cystic or solid lesion, respectively. The most common referral query was regarding the management plan (349/522; 66.9%). Endoscopy was the procedure most often proposed before MDT discussion (109/522; 20.9%). Overall, the MDT discussion led to modification of the management plan in 377/522 patients (72.2%), with a statistically significant difference between cystic and solid lesions (63.2% vs. 77.2%; P<0.001). Management modifications were mainly driven by revision of cross-sectional radiological images. MDT discussion led to modification of the diagnosis in 92/522 patients (17.6%), with a significant difference regarding cystic lesions (35.7% vs. 7.7%; P<0.001). Conclusion: MDT discussion impacts the management of patients with cystic and solid pancreatic lesions, leading to a modification of the initially proposed management in two-thirds of them, mainly through revision of cross-sectional imaging.

Perioperative antimicrobial prophylaxis in patients undergoing pancreatoduodenectomy: retrospective analysis of bacteriological profile and susceptibility.

BACKGROUND: Pancreatic tumours are frequently associated with obstructive jaundice requiring preoperative biliary drainage (PBD) before pancreatoduodenectomy (PD), exposing patients to infectious complications. This study aims to compare postoperative complications after PD with or without PBD and to analyse bile bacteriology and antibiotic susceptibility. METHODS: All patients undergoing PD between 2014 and 2019 were retrospectively evaluated, and postoperative outcomes were compared according to PBD use. Prophylactic narrow-spectrum antibiotic therapy was given for 24 h, then adapted according to bacteriologic profile. Intraoperative bile cultures and antibiograms were collected. RESULTS: Among 164 patients with intraoperative bile culture during PD (75 PBD+, 89 PBD-), an infected bile was observed in 95% and 70% of PBD + and PBD- groups, respectively (p < 0.001). Postoperative mortality and severe morbidity including infectious complications were similar between groups (5% and 15%). The median duration of antibiotherapy was longer in PBD + compared to PBD- groups (9 vs. 2 days, p = 0.009). Malignant indication and PBD were associated with bile contamination using univariate analysis, and PBD was significantly relevant at multivariate analysis. Most common pathogens identified in bile cultures were Escherichia coli, Klebsiella spp. and Enterobacter spp. Overall antibiotic susceptibility to commonly used antibiotics was decreased, including those used in our local guidelines. CONCLUSIONS: PBD exposes nearly 100% of patients undergoing PD to bile infection and an increased duration of postoperative antimicrobial therapy, without increasing infectious complications in this study. Adaptation of antimicrobial prophylaxis should be further evaluated according to performance of PBD and local epidemiology, in order to avoid overuse of antibiotics.

Soft self-expandable metal stent to treat painful pancreatic duct strictures secondary to chronic pancreatitis: a prospective multicenter trial.

BACKGROUND AND AIMS: Fully covered self-expandable metal stents (FCSEMSs) may offer a treatment option for pain associated with a dilated pancreatic duct (PD) in chronic pancreatitis (CP), but optimal patient selection and FCSEMS design, efficacy, and safety remain uncertain. We studied an investigational pancreatic FCSEMS for treatment of CP-associated pain. METHODS: Patients with painful CP, a dominant distal PD stricture, and PD dilation upstream were enrolled in a prospective, multicenter, single-arm trial studying 6-month indwell of a 4- to 6-cm-long soft pancreatic FCSEMS. Primary efficacy and safety endpoints were pain reduction 6 months after FCSEMS indwell (performance goal ≥53%) and PD stenting-related serious adverse events (SAEs), respectively (performance goal <32%). The primary efficacy endpoint was assessed in patients with sufficiently severe and frequent pain at FCSEMS placement as a first stent or in exchange of a plastic stent. RESULTS: Among 67 patients (mean age, 52.7 ± 12.5 years; mean time since CP diagnosis, 6.4 ± 6.4 years), 34 (50.7%) had plastic stent placement within 90 days of FCSEMS placement, and 46 patients were eligible for the primary efficacy endpoint analysis. Technical success was 97.0% (65/67). The observed primary efficacy (26.1%, 12/46) and safety endpoints (31.3%, 21/67) failed to meet the a priori study hypotheses. Study stent migration occurred in 47.7% of patients (31/65). CONCLUSIONS: Six-month treatment with an FCSEMS did not lead to an expected degree of pain reduction, and migrations and SAEs were common. Further study is needed to clarify optimal decompressive strategy, FCSEMS design, and patient selection. (Clinical trial registration number: NCT02802020.).

Primary Helicobacter pylori resistance to antimicrobials in the Brussels area in 2021.

This manuscript summarizes current primary resistance of Helicobacter pylori to antibiotics in Brussels in 2021. Resistance rates were estimated at 18% for clarithromycin, 24% for levofloxacin, 52% for metronidazole, and 0% for amoxicillin and tetracycline. When compared to 2016, resistance rates remain stable, except an increase of 30% for metronidazole.

Endoscopic internal drainage of complex bilomas and biliary leaks by transmural or transpapillary/transfistulary access.

BACKGROUND AND AIMS: Bilomas most frequently result from postoperative bile leaks. The endoscopic conventional treatment is sphincterotomy ± stent placement. In complex cases, such as altered anatomy or failure of conventional treatment, transpapillary/transfistulary (TP/TF) drainage or EUS-guided transmural drainage (EUS-TD) may obviate additional biliary surgery. This study reports our experience with treating biloma secondary to refractory biliary leak with TP/TF drainage or EUS-TD and evaluates the safety and outcomes associated with this approach. METHODS: This observational study focused on consecutive patients managed for biliary leakage (diagnosis based on imaging and/or bile outflow from a surgical drain) at a tertiary care hospital (2007-2017). TP/TF drainage was performed by double-pigtail stent(s) placement to drain the biloma through the leak during ERCP. For EUS-TD, plastic stent(s) were placed under EUS control. Primary outcomes were a composite of clinical success (patient free of sepsis after percutaneous drain removal and, in patients with benign disease, removal of all endoscopically placed stents, without need for reintervention) and biloma regression (<3 cm) at last follow-up. RESULTS: Thirty patients (men, 57%; median age, 55 years) were included. Most biliary leaks resulted from cholecystectomy (27%) and hepatectomy (50%). Initial EUS-TD and TP/TF drainage were performed in 14 (47%) and 16 (53%) patients, respectively. At last follow-up (median, 33.2 months), clinical success and primary outcome were achieved in 70.4% of patients (EUS-TD, 75%; TP/TF, 67%). Additional surgery was necessary in 1 patient. Rate of serious adverse events was 23% (7/30), of which 13% (4/30) were procedure related. There were 4 deaths during the course of treatment, 2 of which were related to endoscopic interventions (hemorrhage and fibrillation). CONCLUSIONS: TP/TF drainage or EUS-TD is technically feasible with high clinical success and may avoid the need for additional surgery in complex cases or in patients with altered anatomy.

Undifferentiated Pancreatic Carcinoma With Osteoclast-Like Giant Cells: What Do We Know So Far?

Undifferentiated carcinoma of the pancreas is an aggressive but rare tumor for which several other terms have been used to describe its histological appearance. In addition, as osteoclast-like giant cells may accompany undifferentiated carcinoma of the pancreas, the WHO Classification distinguishes undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) from plain undifferentiated carcinoma since there are a few histopathological and clinical differences. UC-OGC was initially thought to be associated with worse prognosis compared to invasive ductal pancreatic adenocarcinoma, since it is often unresectable at diagnosis and tends to recur rapidly even if completely resected. When true UC-OGGs are carefully dissected out from other anaplastic carcinomas, it becomes, however, clear that UC-OGCs do have more indolent behavior, especially the pure UC-OGCs. This mini-review summarizes the current knowledge on UC-OGC.

Implementation of colonoscopy quality monitoring in a Belgian university hospital with integrated computer-based extraction of adenoma detection rate.

Background and study aims Quality in colonoscopy has been promoted in last decade with definition of different quality indicators (QI) as benchmarks. Currently, automatized monitoring systems are lacking, especially for merging pathologic and endoscopic data, which limits quality monitoring implementation in daily practice. We describe an adapted endoscopy reporting system that allows continuous QI recording, with automatic pathological data inclusion. Material and methods We locally adapted a reporting system for colonoscopy by adding and structuring in a dedicated tab selected key QI. Endoscopic data from a reporting system and pathological results were extracted and merged in a separate database. During the initial period of use, performing physicians were encouraged to complete the dedicated tab on a voluntary basis. In a second stage, completing of the tab was made mandatory. The completeness of QI recording was evaluated across both periods. Performance measures for all endoscopists were compared to global results for the department and published targets. Results During the second semester of 2017, a total of 1827 colonoscopies were performed with a QI tab completed in 100 % of cases. Among key QI, the cecal intubation rate was 93.8 %, the rate of colonoscopies with adequate preparation was 90.7 %, and the adenoma detection rate was 29.8 % considering all colonoscopies, irrespective of indication; 28.8 % considering screening procedures; and 36.6 % in colonoscopies performed in people older than age 50 years. Conclusion This study shows that quality monitoring for colonoscopy can be easily implemented with limited human resources by adapting a reporting system and linking it to a pathology database.

Liquid Biopsy of Bile based on Targeted Mass Spectrometry for the Diagnosis of Malignant Biliary Strictures.

Bile holds biomarkers of malignant biliary strictures (MBS) but is unsuited for automated analyzers used in routine diagnostic laboratories. Selected reaction monitoring (SRM) is a flexible high-throughput analytical approach based on targeted mass spectrometry (MS) already implemented in clinical settings. We tested the hypothesis that SRM could be used to quantify cancer biomarkers in human bile. An SRM-based assay was developed to simultaneously quantify up to 37 peptides from 13 bile proteins in a developmental cohort of 15 patients (MBS, n = 8; benign biliary stricture or obstruction (BBS), n = 7). The most reliable biomarkers were then absolutely quantified by SRM in a verification cohort of 67 patients (MBS, n = 37; BBS, n = 30). The diagnostic performances of single and combined biomarkers were assessed. In the developmental cohort, SRM-based analysis revealed six protein biomarkers with significantly higher peptide ratios (endogenous vs. standard) in bile from MBS vs. BBS. In the verification cohort, five of these biomarkers proved good diagnostic ability (individual receiver operating characteristic-area under the receiver operating characteristic curve (ROC-AUC) up to 0.889, accuracies from 67.8% to 83.1%). Combining bile biomarkers and serum CA19-9 in 2 panels allowed differentiating MBS from BBS with up to 0.929 ROC-AUC and 89.8% accuracy. In this study, a newly developed SRM-based assay proved able to simultaneously quantify multiple biomarkers in bile samples. The combination of bile biomarkers with serum CA19-9 was highly accurate for the diagnosis of MBS. Liquid biopsy of bile based on targeted MS is eligible to support MBS diagnosis in clinical practice.

Indwelling double-pigtail plastic stents for treating disconnected pancreatic duct syndrome-associated peripancreatic fluid collections: long-term safety and efficacy.

BACKGROUND: Long-term transmural double-pigtail stent (DPS) placement is recommended for patients with disconnected pancreatic duct syndrome (DPDS) and peripancreatic fluid collections (peri-PFCs). The long-term safety and efficacy of indwelling DPSs were evaluated. METHODS: Medical files of patients treated with DPS for DPDS-associated peri-PFC and with a follow-up ≥ 48 months were reviewed. Early ( < 30 days) and late complications of DPS placement were evaluated and the primary endpoint, i. e., incidence of late complications per 100 patient-years of follow-up, was calculated. Short- and long-term success rates of endoscopic treatment and rate of peri-PFC recurrence were among secondary endpoints. RESULTS: From 2002 to 2014 we identified 116 patients, with mean (SD) follow-up of 80.6 (34.4) months. Among early complications (n = 20), 6 occurred peri-interventionally. Late complications (n = 17) were mainly pain due to DPS-induced ulcer or erosion (n = 10) and 14 of these were treated conservatively or by stent removal; 2 gastro-pancreatico-colo-cutaneous fistulas and 1 persisting bleed required surgical intervention. No DPS-related deaths were recorded. The incidence rate (95 %CI) of late complications was 2.18 (1.27-3.49) per 100 patient-years of follow-up. Short- and long-term success rates (with 95 %CI) of endoscopic treatment were 97.4 % (94.5 %-100 %) and 94 % (89.6 %-98.3 %), respectively. The peri-PFC recurrence rate was 28 % (20.1 %-35.9 %), and 92.3 % of these occurred within the first 2 years. Stent migration, chronic pancreatitis, and length of stent (> 6 cm) were independently associated with higher rates of peri-PFC recurrence. CONCLUSIONS: Long-term transmural drainage with DPS is a safe and effective treatment for DPDS-associated peri-PFCs. However, about one quarter of peri-PFCs will recur.

Biliary cast syndrome after liver transplantation: A cholangiographic evolution study.

BACKGROUND AND AIM: The aim of this study is to describe the cholangiographic features and endoscopic management of biliary cast syndrome (BCS), a rare specific ischemic cholangiopathy following liver transplantation. METHODS: Patients with biliary complications were identified from prospectively collected database records of patients who underwent liver transplantation at the Erasme Hospital from January 2005 to December 2014. After excluding patients with hepatico-jejunostomy or no suspicion of stricture, cholangiograms obtained during endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance imaging were systematically reviewed. Biliary complications were categorized as anastomotic (AS) and non-AS strictures, and patients with BCS were identified. Clinical, radiological, and endoscopic data were reviewed. RESULTS: Out of 311 liver transplantations, 14 cases were identified with BCS (4.5%) and treated with ERCP. Intraductal hyperintense signal on T1-weighted magnetic resonance and a "duct-in-a-duct" image were the most frequent features of BCS on magnetic resonance imaging. On initial ERCP, 57% of patients had no stricture. Complete cast extraction was achieved in 12/14, and one of these had cast recurrence. On follow-up, 85% of the patients developed biliary strictures that were treated with multiple plastic stents reaching 60% complete stricture resolution, but 40% of them had recurrence. After a median follow-up of 58 months, BCS patients had lower overall and graft survival (42.9% and 42.9%) compared with non-AS (68.8% and 56.3%) and AS (83.3% and 80.6%), respectively. CONCLUSIONS: Particular magnetic resonance-cholangiographic and ERCP-cholangiographic features of BCS have been identified. Outcomes for BCS are characterized by high complete cast extraction rates, high incidence of secondary strictures, and poorer prognosis.

Challenging biliary strictures: pathophysiological features, differential diagnosis, diagnostic algorithms, and new clinically relevant biomarkers - part 1.

It is frequently challenging to make the correct diagnosis in patients with biliary strictures. This is particularly important as errors may have disastrous consequences. Benign-appearing strictures treated with stents may later be revealed to be malignant and unnecessary surgery for benign strictures carries a high morbidity rate. In the first part of the review, the essential information that clinicians need to know about diseases responsible for biliary strictures is presented, with a focus on the most recent data. Then, the characteristics and pitfalls of the methods used to make the diagnosis are summarized. These include serum biomarkers, imaging studies, and endoscopic modalities. As tissue diagnosis is the only 100% specific tool, it is described in detail, including techniques for tissue acquisition and their yields, how to prepare samples, and what to expect from the pathologist. Tricks to increase diagnostic yields are described. Clues are then presented for the differential diagnosis between primary and secondary sclerosing cholangitis, IgG4-related sclerosing cholangitis, cholangiocarcinoma, pancreatic cancer, autoimmune pancreatitis, and less frequent diseases. Finally, algorithms that will help to achieve the correct diagnosis are proposed.

Non-occlusive Mesenteric Ischemia as a Fatal Complication in Acute Pancreatitis: A Case Series.

BACKGROUND: Vascular complications of severe acute pancreatitis are well known and largely described unlike non-occlusive mesenteric ischemia, which is a rare and potentially fatal complication. Non-occlusive mesenteric ischemia is an acute mesenteric ischemia without thrombotic occlusion of blood vessels, poorly described as a complication of acute pancreatitis. METHODS: We retrospectively reviewed a prospectively maintained registry of all pancreatic diseases referred to our center from 2013 to 2018, in order to determine the causes of early death. We identified three patients who died within 48 h after hospital admission from severe acute pancreatitis complicated by irreversible non-occlusive mesenteric ischemia. Their clinical presentation, management, and outcomes were herein reported. RESULTS: Three consecutive patients with severe acute pancreatitis developed non-occlusive mesenteric ischemia within the first 5 days after onset of symptoms and died 48 h after non-occlusive mesenteric ischemia diagnosis despite optimal intensive care management and surgery, giving a prevalence of 3/609 (0.5%). Symptoms were unspecific with consequently potential delayed diagnosis and management. High doses of norepinephrine required for hemodynamic support (n = 3) potentially leading to splanchnic vessels vasoconstriction, transient hypotension (n = 3), and previous severe ischemic cardiomyopathy (n = 1) could be involved as precipitating factors of non-occlusive mesenteric ischemia. CONCLUSION: Non-occlusive mesenteric ischemia can be a fatal complication of acute pancreatitis but is also challenging to diagnose. Priority is to reestablish a splanchno-mesenteric perfusion flow. Surgery should be offered in case of treatment failure or deterioration but is still under debate in early stage, to interrupt the vicious circle of intestinal hypoperfusion and ischemia.

Multiple stents are not superior to single stent insertion for pain relief in patients with chronic pancreatitis: a retrospective comparative study.

Background and study aims Patients with painful chronic pancreatitis (CP) and distal main pancreatic duct (MPD) stricture are considered candidates for treatment using a single plastic stent insertion. Multiple side-by-side stents have been proposed as an alternative treatment but comparative studies are lacking. The aim of this retrospective study is to assess differences in characteristics and treatment outcomes in patients with CP and MPD strictures treated with a different number of stents during the stenting period. Patients and methods Patients with painful CP and distal MPD obstruction requiring endoscopic treatment (01.2004 - 12.2012) were considered. The study population was divided in three groups: Patients treated with (A) exclusively one stent; (B) one or two stents; and (C) exclusively two stents during the stenting period. Patient characteristics and treatment outcomes were retrospectively assessed. Results Among 284 patients, 85 were selected according to inclusion criteria (Group A: 18, Group B: 35, Group C: 32). Median follow-up duration was 84 months. The median number of endoscopic procedures needed was higher for group B [3 (A) vs. 3 (C) vs. 4 (B), P  = 0.001]. Regarding outcome, successful endoscopic treatment was lower in Group C (50 % vs. 88.2 % and 74.2 % for groups A and B, respectively; P  = 0.02). This difference was attributed to better clinical outcome in Group A compared to Group C patients [OR(95%CI): 7.50 (1.46 - 38.70); P  = 0.04]. Moreover, group C patients experienced higher levels of pain at the end of follow-up period [median Izbicki Score 0 (group A) vs. 0 (group B) vs. 6 (group C), P  = 0.03]. Conclusions In patients with painful CP and distal MPD obstruction, treatment with a single stent is associated with better clinical outcome compared to treatment with exclusively two stents during the stenting period.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Updated August 2018.

ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team and surgical options should be considered.Weak recommendation, low quality evidence.ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting.Weak recommendation, low quality evidence.ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence.ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL.Weak recommendation, moderate quality evidence.ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence.ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach.Strong recommendation, moderate quality evidence.ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome.Strong recommendation, low quality evidence.ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures.Weak recommendation, moderate quality evidence.ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange.Strong recommendation, low quality evidence.

Pain in pancreatic ductal adenocarcinoma: A multidisciplinary, International guideline for optimized management.

Abdominal pain is an important symptom in most patients with pancreatic ductal adenocarcinoma (PDAC). Adequate control of pain is often unsatisfactory due to limited treatment options and significant variation in local practice, emphasizing the need for a multidisciplinary approach. This review contends that improvement in the management of PDAC pain will result from a synthesis of best practice and evidence around the world in a multidisciplinary way. To improve clinical utility and evaluation, the evidence was rated according to the GRADE guidelines by a group of international experts. An algorithm is presented, which brings together all currently available treatment options. Pain is best treated early on with analgesics with most patients requiring opioids, but neurolytic procedures are often required later in the disease course. Celiac plexus neurolysis offers medium term relief in a substantial number of patients, but other procedures such as splanchnicectomy are also available. Palliative chemotherapy also provides pain relief as a collateral benefit. It is stressed that the assessment of pain must take into account the broader context of other physical and psychological symptoms. Adjunctive treatments for pain, depression and anxiety as well as radiotherapy, endoscopic therapy and neuromodulation may be required in selected patients. There are few comparative studies to help define which combination and order of these treatment options should be applied. New pain therapies are emerging and could for example target neural transmitters. However, until better methods are available, management of pain should be individualized in a multidisciplinary setting to ensure optimal care.

Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines.

1: ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2: ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3: ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4: ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5: ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6: ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7: ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8: ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence.

Guidelines for the understanding and management of pain in chronic pancreatitis.

Abdominal pain is the foremost complication of chronic pancreatitis (CP). Pain can be related to recurrent or chronic inflammation, local complications or neurogenic mechanisms with corresponding changes in the nervous systems. Both pain intensity and the frequency of pain attacks have been shown to reduce quality of life in patients with CP. Assessment of pain follows the guidelines for other types of chronic pain, where the multidimensional nature of symptom presentation is taken into consideration. Quantitative sensory testing may be used to characterize pain, but is currently used in a research setting in advanced laboratories. For pain relief, current guidelines recommend a simple stepwise escalation of analgesic drugs with increasing potency until pain relief is obtained. Abstinence from alcohol and smoking should be strongly advised. Pancreatic enzyme therapy and antioxidants may be helpful as initial treatment. Endoscopic treatment can be used in patients with evidence of ductal obstruction and may be combined with extracorporeal shock wave lithothripsy. The best candidates are those with distal obstruction of the main pancreatic duct and in early stage of disease. Behavioral interventions should be part of the multidisciplinary approach to chronic pain management particularly when psychological impact is experienced. Surgery should be considered early and after a maximum of five endoscopic interventions. The type of surgery depends on morphological changes of the pancreas. Long-term effects are variable, but high success rates have been reported in open studies and when compared with endoscopic treatment. Finally, neurolytical interventions and neuromodulation can be considered in difficult patients.