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Importance: Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach., Objective: To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial., Design, Setting, and Participants: Between April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023., Exposure: Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach., Main Outcomes and Measures: The primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle., Results: In this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were "very satisfied" with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28])., Conclusions and Relevance: In this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function., Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes., Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018., Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed., Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality., Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach., Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings., Trial Registration: ISRCTN Identifier: ISRCTN45877994.

Introduction: Chronic pancreatitis (CP) is a progressive inflammatory disorder causing irreversible destruction of pancreatic tissue, leading to malnutrition. A previous study has found that currently used screening methods (periodic recording of body weight and faecal and serological markers) fall short in identifying and curbing malnutrition. Moreover, data is lacking regarding change in nutritional status over time. The aim of our study is to investigate changes in nutritional status in CP patients over time and to determine whether a more extensive set of measurements would be beneficial for nutritional screening of these patients., Methods: CP patients who had undergone a nutritional assessment in 2012 were recruited to undergo a second assessment. The assessment consisted of anthropometric measurements, bioelectrical impedance analysis (BIA), handgrip strength (HGS), the Mini Nutritional Assessment (MNA), determination of faecal and serological markers and the Short Form Health (SF-36) questionnaire. These two assessments were compared and correlations between the various measures were calculated., Results: Twenty-eight patients underwent a second assessment. An increase in fat mass and a decrease in both fat free mass (FFM) and HGS were observed. The number of patients scoring under the 10th percentile for FFM (43%-54%) and HGS in their dominant side (38%-46%) increased. FFM and HGS were positively correlated (R = 0.57)., Conclusion: Even though current guidelines for CP follow-up were adhered to, there was a general deterioration in nutritional status. HGS correlated with FFM. HGS might be useful as a screening instrument for malnutrition in CP patients., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP., Methods: The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness., Discussion: The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs., Trial Registration: EudraCT: 2015-000829-37 . Registered on 18 February 2015., Isrctn: 13659155 . Registered on 18 May 2015.

Three patients, two women aged 33 and 75 years and a 62-year-old man, presented with gallstones and upper abdominal pain due to functional dyspepsia, chronic constipation, and oesophageal spasm, respectively. After a period of watchful waiting, the first patient insisted on having a cholecystectomy, but her complaints persisted. In the second patient, the complaints disappeared after treatment with a bulking agent and magnesium oxide. The third patient received medication as well: a proton-pump inhibitor, prokinetic agents, a calcium antagonist and Helicobacter eradication, and recovered. The presence of gallstones is relatively easy to assess by ultrasound imaging, but the decision whether abdominal symptoms are related to gallbladder stones remains a diagnostic challenge for the clinician. The key question for the family practitioner, gastroenterologist and surgeon is which patients with upper abdominal pain and proven gallbladder stones might benefit from a cholecystectomy. The patients described illustrate that upper abdominal pain is not invariably related to symptomatic gallbladder disease. The published evidence supports initial watchful waiting with additional diagnostic investigation, and cholecystectomy only later if judged to be necessary.

Objective: To assess the impact of bile duct injury (BDI) sustained during laparoscopic cholecystectomy on physical and mental quality of life (QOL)., Summary Background Data: The incidence of BDI during laparoscopic cholecystectomy has decreased but remains as high as 1.4%. Data on the long-term outcome of treatment in these patients are scarce, and QOL after BDI is unknown., Methods: One hundred six consecutive patients (75 women, median age 44 +/- 14 years) were referred between 1990 and 1996 for treatment of BDI sustained during laparoscopic cholecystectomy. Outcome was evaluated according to the type of treatment used (endoscopic or surgical) and the type of injury. Objective outcome (interventions, hospital admissions, laboratory data) was evaluated, a questionnaire was filled out, and a QOL survey was performed (using the SF-36). Risk factors for a worse outcome were calculated., Results: Median follow-up time was 70 months (range 37-110). The objective outcome of endoscopic treatment (n = 69) was excellent (94%). The result of surgical treatment (n = 31) depended on the timing of reconstruction (overall success 84%; in case of delayed hepaticojejunostomy 94%). Five patients underwent interventional radiology with a good outcome. Despite this excellent objective outcome, QOL appeared to be both physically and mentally reduced compared with controls (P <.05) and was not dependent on the type of treatment used or the severity of the injury. The duration of the treatment was independently prognostic for a worse mental QOL., Conclusions: Despite the excellent functional outcome after repair, the occurrence of a BDI has a great impact on the patient's physical and mental QOL, even at long-term follow-up.

Background/aims: Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients., Methods: Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined., Results: Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction., Conclusions: Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

Eight years after the introduction of laparoscopic cholecystectomy a decrease of the incidence of bile duct injuries is reported in the literature. The incidence of a bile duct injury after laparoscopic cholecystectomy is now slightly higher than after open cholecystectomy. A minority of these injuries are detected during surgery. Most patients have a delayed identification of the bile duct injury, even after discharge from the hospital. An early diagnostic work-up with ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) is mandatory in every patient with persisting symptoms (more than 48 hours) after laparoscopic cholecystectomy. Still, one-third of the patients are subjected to a 'diagnostic' exploratory laparotomy without preoperative visualization of the biliary tract by ERCP or percutaneous transhepatic cholangiography. Minor lesions are mostly treated successfully by endoscopy with a stent. After transection of the bile duct surgical reconstruction by a hepaticojejunostomy has to be performed. A delayed elective reconstruction was associated with fewer complications than acute repair under suboptimal circumstances such as local inflammatory changes and bile leakage.

Objective: To determine the feasibility and desirability of laparoscopic cholecystectomy (LC) in day-care versus LC with clinical observation., Summary Background Data: Laparoscopic cholecystectomy has been performed regularly as outpatient surgery in patients with uncomplicated gallstone disease in the United States, but this has not been generally accepted in Europe. The main objections are the risk of early severe complications (bleeding) or other reasons for readmission, and the argument that patients might feel safer when observed for one night. Quality-of-life differences hitherto have not been investigated., Methods: Eighty patients (American Society of Anesthesiology [ASA] I/II) with symptomatic gallstones were randomized to receive LC either in day-care or with clinical observation. Complications, (re)admissions, consultations of general practitioners or the day-care center within 4 days after surgery, use of pain medication, quality of life, convalescence period, time off from professional activities, and treatment preference were assessed. The respective costs of day-care and clinical observation were determined., Results: Of the 37 patients assigned to the day-care group who underwent elective surgery, 92% were discharged successfully after an observation period of 5.7+/-0.2 hours. The remainder of the patients in this group were admitted to the hospital and clinically observed for 24 hours. For the 37 patients in the clinical observation group who underwent elective surgery, the observation time after surgery was 31+/-3 hours. Three patients in the day-care group and one patient in the clinical observation group had complications after surgery. None of the patients in either group consulted a general practitioner or the hospital during the first week after surgery. Use of pain medication was comparable in both groups over the first 48 hours after surgery. There were no differences in pain and other quality-of-life indicators between the groups during the 6 weeks of follow-up. Of the patients in the day-care group, 92% preferred day-care to clinical observation. The same percentage of patients in the clinical observation group preferred at least 24 hours of observation to day-care. Costs for the day-care patients were substantially lower (approximately $750/patient) than for the clinical observation patients., Conclusion: Effectiveness was equal in both patient groups, and both groups appeared to be satisfied with their treatment. Because no differences were found with respect to the other outcomes, day-care is the preferred treatment in most ASA I and II patients because it is less expensive.

Background: Previous studies have suggested that improvements in diagnostic workup and treatment of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy can be expected as experience increases with the laparoscopic procedure. Many published articles reported that early diagnosis, proper classification, and optimal timing of treatment of BDI increase the likelihood of successful treatment. This study determined whether diagnosis and management of BDI have improved over the years., Study Design: Between June 1990 and November 1996, 106 patients were diagnosed and treated in the Amsterdam Academic Medical Center for BDI sustained during laparoscopic cholecystectomy. Detailed information was obtained about peroperative findings, time interval from laparoscopic cholecystectomy to symptoms, and interval from symptoms to diagnosis. Bile duct injuries were classified into four types. Two patient groups were compared: BDI patients diagnosed from 1990 until 1994 ("learning phase") and patients diagnosed from 1995 until 1996., Results: Bile duct injuries combined with bile leakage were diagnosed significantly earlier in the second period after the learning phase. The percentages of injuries diagnosed peroperatively, "blind laparotomies," and suboptimal timed hepaticojejunostomies were not different between the groups., Conclusions: Except for earlier diagnosis of BDI in the later period than in previous years, there appeared to be no significant improvement in diagnostic workup and management during the past 2 years.

Many studies have demonstrated that gallbladder bile (but not hepatic bile) of animals or patients with cholesterol gallstones contains higher protein concentrations than does gallbladder bile of control patients without stones or with pigment stones. The underlying defect has not been elucidated. To establish whether there is net production or net absorption/degradation of protein by gallbladder epithelium for different classes of protein, paired samples of hepatic and gallbladder bile were obtained from fourteen patients with cholesterol gallstones during elective cholecystectomy. In these paired samples, lipid and protein composition were determined. To obtain the concentration ratio (CR) of protein and lipid, its concentration in the gallbladder was divided by the concentration determined in the paired hepatic bile sample. The CR of bile salts was used as a parameter for water absorption in the gallbladder. Of the biliary proteins that were determined only mucin, albumin, immunoglobulin (Ig) G, and aminopeptidase N appeared to increase in the gallbladder from another cause than water absorption. A strong correlation was found between mucin, albumin, and IgG. Haptoglobin, alpha1-acid glycoprotein, IgM, and IgA appeared to be absorbed by gallbladder epithelium in the majority of patients. In cholesterol gallstone patients, total protein concentration in gallbladder bile of cholesterol gallstone patients is increased when compared with hepatic bile. The increase in protein concentration cannot be explained for all bile samples solely by water absorption. In this study we show that the defect is largely caused by a selective increase in albumin, mucin, and IgG. All other proteins which were investigated are taken up by the gallbladder.