Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis.

Endoscopic ultrasound (EUS) with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and autoimmune pancreatitis or to analyze cyst fluid. The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis, which is likely induced by the same pathophysiological mechanisms as after endoscopic retrograde cholangiopancreatography (ERCP). According to the current European Society of Gastrointestinal Endoscopy guideline, nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate. A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition (TA) is harmless in healthy adults. Since it is associated with low costs and, most important, may prevent a dreadsome complication, we strongly recommend the administration of 100 mg diclofenac rectally prior to EUS-TA. We will explain this recommendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Long-term follow-up study of necrotising pancreatitis: interventions, complications and quality of life.

OBJECTIVE: To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life. DESIGN: Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed. RESULTS: During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up. CONCLUSION: Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up.

Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

BACKGROUND AND AIMS: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.

Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study.

OBJECTIVE: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings. DESIGN: A multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013-2017) applying the same study design. RESULTS: Overall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17-23) after hospital presentation and at a median of 29 hours (IQR 23-41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92). CONCLUSION: In patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group. TRIAL REGISTRATION NUMBER: ISRCTN15545919.

Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial.

BACKGROUND: Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS: Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS: 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION: DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

Endoscopic retrograde pancreatography-guided versus endoscopic ultrasound-guided technique for pancreatic duct cannulation in patients with pancreaticojejunostomy stenosis: a systematic literature review.

BACKGROUND: Stenosis of the pancreaticojejunostomy is a well-known long-term complication of pancreaticoduodenectomy. Traditionally, the endoscopic approach consisted of endoscopic retrograde pancreatography (ERP). Endoscopic ultrasound (EUS)-guided intervention has emerged as an alternative, but the success rate and adverse event rate of both treatment modalities are poorly known. We aimed to compare the outcome data of both interventions. METHODS: We performed a systematic literature search using the Pubmed/Medline and Embase databases in order to summarize the available data regarding efficacy and complications of ERP- and EUS-guided pancreatic duct (PD) drainage and compare these outcome data using uniform outcome measures in a multilevel logistic model. RESULTS : 13 studies were included, involving 77 patients who underwent ERP-guided drainage, 145 who underwent EUS-guided drainage, and 12 patients who underwent both modalities. An EUS-guided approach was significantly superior to an ERP-guided approach with regard to pancreatic duct opacification (87 % vs. 30 %; P < 0.001), cannulation success (79 % vs. 26 %; P < 0.001), and stent placement (72 % vs. 20 %; P < 0.001). An EUS-guided approach also appeared superior with regard to clinical outcomes such a pain resolution. The adverse event rate between the two treatment modalities could not be compared due to insufficient data. All included studies were found to be of low quality. CONCLUSION: Based on limited available data, EUS-guided PD intervention appears superior to ERP-guided PD intervention.

Pain patterns in chronic pancreatitis: a nationwide longitudinal cohort study.

OBJECTIVE: Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study. DESIGN: 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model. RESULTS: At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain. CONCLUSION: Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced.

SpyGlass DS-guided lithotripsy for pancreatic duct stones in symptomatic treatment-refractory chronic calcifying pancreatitis.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shock wave lithotripsy are first-line therapies for draining an obstructed pancreatic duct (PD) in painful chronic calcifying pancreatitis (CCP). Pancreaticoscopy has shown promising success rates in small series. Materials and methods This study was a retrospective analysis of a clinical database. Included were all digital single-operator digital video (SOV) pancreaticoscopy-guided interventions (n = 23) on CCP patients (n = 20) between 2015 and 2017. Success and complication rates were collected from the database. Clinical success was determined by assessing pain level score (NRS) and quality of life (QoL) using standardized questionnaires. Results Overall technical success rate (successful SOV-pancreaticoscopy and PD drainage) was 95 %. Adverse events occurred in 7 of 23 procedures (30 %) and included extravasation from the PD (n = 1), self-limiting post-sphincterotomy bleeding (n = 1) and post-ERCP pancreatitis (PEP) (n = 6). At 3- to 6-month follow-up, 95 % of patients reported improvement in symptoms and reduction in intake of analgesics. Mean NRS decreased from 5.4 (±1.6) to 2.8 (± 1.8) ( P  < 0.01). Clinical success was achieved in 95 % of patients. Conclusions Digital SOV-guided lithotripsy was found to be safe and effective in this highly selected population of CCP patients. PD decompression had a beneficial effect on pain reduction and QoL.

Lack of consensus on the role of endoscopic retrograde cholangiography in acute biliary pancreatitis in published meta-analyses and guidelines: a systematic review.

OBJECTIVES: Several randomized controlled trials studied the role of endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic sphincterotomy (ES) in acute biliary pancreatitis (ABP). No study assessed whether these trials resulted in international consensus in published meta-analyses and treatment guidelines. METHODS: A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of meta-analyses and guidelines on ERCP in ABP was performed in PubMed until August 2011.The methodological quality of the meta-analysis and guidelines was assessed by a validated quality assessment tool. RESULTS: Eight meta-analyses and 12 guidelines fulfilled the inclusion criteria. There is consensus that ERCP is indicated in case of ABP with coexistent cholangitis and/or persistent cholestasis. By exception of the first meta-analysis, all included studies disapproved early ERCP in predicted mild ABP. Consensus is lacking regarding the role of early ERCP in predicted severe ABP, as 3 meta-analyses and 1 guideline do not advice this strategy. Routine early ERCP in predicted severe ABP is recommended in 7 of the 11 guidelines. CONCLUSIONS: There is consensus in guidelines and meta-analyses that ERCP/ES is indicated in patients with ABP and coexisting cholangitis and/or persistent cholestasis. Consensus is lacking on the role of routine early ERCP/ES in patients with predicted severe ABP.

Infliximab in Crohn's disease-associated toxic megacolon.

Refractory medical treatment of Crohn disease-associated toxic megacolon usually requires surgery, which carries substantial morbidity and mortality. We report a case of a woman with steroid and antibiotic-refractory fulminant Crohn colitis and ileitis, complicated by a toxic megacolon, who was successfully treated with infliximab. Infliximab induced rapid clinical response and remission, thereby avoiding emergency (ileo) colectomy. This is the first report of treatment of Crohn disease-associated toxic megacolon with infliximab.

Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease.

OBJECTIVES: Obesity and insulin resistance cause fatty infiltration of many organs, including the pancreas (pancreatic steatosis [PS]) and the liver (nonalcoholic fatty liver disease [NAFLD]). In contrast to NAFLD, pathophysiological mechanisms and clinical relevance of PS remain unknown. This study aimed to identify a possible relation between PS and NAFLD. METHODS: In this study including postmortem collected material of 80 patients, clinical and histological data were collected and revised. Patients with hepatic or pancreatic disease and alcohol abuse were excluded. Nonalcoholic fatty liver disease activity score was used for grading the histology of the liver, whereas pancreatic lipomatosis score assessed PS. Ordinal logistic regression was used to analyze correlations. RESULTS: Interlobular and total pancreatic fat were both related to NAFLD activity score in patients without steatogenic medication (P = 0.02 and P = 0.03, respectively). When corrected for body mass index, no relation could be found. Total pancreatic fat was a significant predictor for the presence of NAFLD (P = 0.02). Presence of intralobular pancreatic fat was related to nonalcoholic steatohepatitis; however, total fat was not. CONCLUSIONS: This study demonstrates that NAFLD and PS are related. This relationship seems to be mediated by general obesity. Intralobular pancreatic fat is associated with nonalcoholic steatohepatitis.

Endoscopic treatment of acute biliary pancreatitis: a national survey among Dutch gastroenterologists.

OBJECTIVE: Based on the ampullary obstruction and reflux theory, six endoscopic retrograde cholangiopancreatography (ERCP) studies have investigated the effect of (early) biliary decompression versus conservative management on the course and outcome of patients with acute biliary pancreatitis (ABP) showing inconsistent and contradictory outcomes. We investigated the opinion and attitude of Dutch gastroenterologists regarding the application of (early) ERCP in the clinical management of ABP by means of a nationwide survey. MATERIAL AND METHODS: An anonymous questionnaire was sent to all registered consultant gastroenterologists (n = 283) across the Netherlands. RESULTS: The response rate was 52%. The vast majority of consulting gastroenterologists declared that early ERCP may be indicated in ABP (96.6%). Fourteen percent stated that they always perform ERCP in ABP. The remainder of the respondents consider ERCP only if a concomitant condition is present such as a dilated CBD (95%), co-existent cholangitis (87%), common bile duct stone(s) (CBDS) (72%), jaundice (59%), ampullary stone (68%) or (predicted) severe ABP (35%). About half of the consultant gastroenterologists (51.4%) consider the optimal time point for ERCP in ABP to be within 24 h after admission or symptom onset. If ERCP is performed for suspected APB, 55% of the respondents perform an endoscopic sphincterotomy (ES), regardless of the findings on cholangiography. CONCLUSIONS: The vast majority of Dutch gastroenterologists attest to a role for ERCP in ABP, but indications when to perform ERCP, its timing, and the application of ES vary greatly and are not always in line with the Dutch or other published national guidelines. The results of this survey highlight the need for additional comparative randomized studies to define the role of (early) ERCP in ABP.

Small bowel motility affects glucose absorption in a healthy man.

OBJECTIVE: To investigate the relationship between duodenojejunal motor activity and glucose absorption and to evaluate the effect of modification of duodenojejunal motility on glucose absorption by using the prokinetic drug cisapride. RESEARCH DESIGN AND METHODS: We examined seven healthy males, mean age 22 years, who were treated with cisapride 10 mg t.i.d. and placebo during 3 days in a randomized order, with a 2-week time interval. Duodenojejunal manometry was performed after each treatment on the morning of day 3, using an 18-lumen catheter. A liquid nutrient (3 kcal/min) was administered intraduodenally for 30 min, followed by a bolus of the glucose analog 3-O-methylglucose (3-OMG). Plasma 3-OMG concentrations were measured to assess absorption kinetics. RESULTS: The area under the 3-OMG concentration curve in the first 30 min after infusion was related to the number of antegrade propagated pressure waves (r = 0.49, P < 0.05), but not to the peak concentration, time to peak, and absorption fraction. The mean amplitude of pressure waves was higher during cisapride than placebo (P < 0.05), but the reoccurrence of interdigestive motility, numbers of pressure waves, and propagated pressure waves, as well as 3-OMG absorption characteristics, were not significantly different between the two treatments. During both treatments >60% of antegrade propagated pressure waves were propagated over a very short distance (1.5 cm). CONCLUSIONS: Glucose absorption in the human small intestine is related to short-traveling propagated intestinal contractile activity. Cisapride increases the amplitude of pressure waves, but does not affect the organization of pressure waves or the absorption of 3-OMG.