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Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP)., Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups., Results: In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10., Conclusion: CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Chronic pancreatitis (CP) may cause intermittent or continuous pain and complications requiring invasive interventions. No specific recommendations for surgical interventions have been presented. Our aim was to determine the surgical treatment strategies for the treatment of CP in the Scandinavian and Baltic countries., Methods: This multi-centre cross sectional study included 1327 CP patients from eight centres. The data was gathered from the Scandinavian Baltic Pancreatic Club (SBPC) database. Patients who underwent pancreatic surgery were analysed. The baseline CP population from the eight centres was used as a reference. The information registered included comorbidities, pancreatic function, previous interventions, time and type of surgery and the EORTC-30 quality of life (QOL) questionnaire., Results: Overall, 95/1327 (7%) patients underwent pancreatic surgery. Fifty-one (54%) of these underwent pancreatic surgery for chronic pain (PSCP) and formed the final study group. Median follow-up time was two (range 0-8) years after surgery and seven (1-46) years after diagnosis. The most common surgical procedures were pancreatic resection combined with drainage (54%) followed by pancreatic resections (32%) and drainage procedures (14%). Postoperatively, 47% of the patients were pain free with or without pain medication while 16% had chronic pain episodes, this did not differ from the base CP population. In QOL questionnaires, PSCP patients reported the same QOL but worse social functioning and more symptoms compared to the CP population., Conclusions: Pancreatic surgery for CP is rare: surgical procedures were performed on only 7% of the CP patients in the SBPC database. In half of the patients the indication was pain. Most of these patients underwent endoscopic procedures before surgery. Half of the patients reported being pain-free after surgery., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/objectives: While pain is the predominant symptom of chronic pancreatitis (CP), a subset of patients may experience a painless course. This systematic review aimed to determine the prevalence of primary painless CP., Methods: MEDLINE (PubMed), EMBASE and Web of Science Core Collection databases were searched for published studies through September 15, 2020 that included at least 10 consecutive patients with CP and which reported the number with painless CP. The presence of a history of recurrent acute pancreatitis (RAP), exocrine pancreatic insufficiency (EPI), diabetes mellitus (DM) and pancreatic adenocarcinoma (PA) in the painless CP patients was also recorded. A random effects model was used to determine pooled prevalence estimates with 95% confidence intervals (95% CI)., Results: Among the 5057 studies identified and screened, 42 full-text articles were included in the final analysis. There were a total of 14,277 patients with CP among whom 1569 had painless CP. The pooled prevalence of painless CP was 12% (95% CI 10-15%). Among a subset of studies that reported on calcifications (n = 11), DM (n = 12), EPI (n = 8) and history of RAP (n = 14), the pooled prevalence estimates were 96% (95% CI 73-100%), 51% (95% CI 32-70%), and 47% (95% CI 15-81%), respectively. Alcohol, idiopathic/genetic and other etiologies were attributed to be the cause of painless CP in 32.4%, 56.9% and 8.9% patients, respectively., Conclusion: Approximately one in ten patients with CP have primary painless disease with the majority being attributable to an idiopathic/genetic etiology. Further research is needed to determine the optimal management of these patients., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Pain is the most common symptom in chronic pancreatitis (CP) with a major impact on quality of life. Few validated questionnaires to assess pain in CP exist, and the lack of consensus negatively impacts clinical management, research and meta-analysis. This guideline aims to review generic pain questionnaires for their usability in CP, to outline how pain assessment can be modified by confounding factors and pain types, to assess the value of additional measures such as quality of life, mental health and quantitative sensory testing, and finally to review pain assessment questionnaires used specifically in CP. A systematic review was done to answer 27 questions that followed the PICO (Population; Intervention; Comparator; Outcome) template. Quality of evidence of the statements was judged by Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria. The manuscript was sent for review to 36 experts from various disciplines and continents in a multi-stage Delphi process, and finally reviewed by patient representatives. Main findings were that generic pain instruments are valid in most settings, but aspects of pain are specific for CP (including in children), and instruments have to account for the wide phenotypic variability and development of sensitization of the central nervous system. Side effects to treatment and placebo effects shall also be considered. Some multidimensional questionnaires are validated for CP and are recommended together with assessment of quality of life and psychiatric co-morbidities. This guideline will result in more homogeneous and comprehensive pain assessment to potentially improve management of painful CP., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients., Methods: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores., Results: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status., Conclusions: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors., Methods: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications., Results: The mean age of patients was 53.9 ± 14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004)., Conclusion: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Objectives: Malnutrition is a well-known complication of chronic pancreatitis and alterations in body composition are common in this context. We investigated the prevalence of sarcopenia in patients with chronic pancreatitis, its associated risk factors and health-related outcome., Methods: This was a prospective cohort study of chronic pancreatitis outpatients. Bioelectric impedance was used to measure body composition, and a handheld dynamometer and the timed-up-and-go test characterized muscle function. Several demographic and disease characteristics, including exocrine pancreatic insufficiency (EPI), were analyzed for their association with sarcopenia. The EORCT QLQ-C30 questionnaire was used to document life quality, and associations between sarcopenia and the number of hospital admissions, the number of in-hospital days and survival over the next 12 months were analyzed., Results: A total of 182 patients were enrolled in the study. The prevalence of sarcopenia was 17.0% (95% CI; 11.9-23.3) and 74% of sarcopenic patients had a BMI in the normal or overweight range (BMI >18.5 kg/m 2 ). EPI was an independent risk factor for sarcopenia (OR 3.8 95% CI [1.2-12.5]; p = 0.03). Several QLQ-C30 scales and items were associated with sarcopenia including physical functioning (p < 0.001) and global health (p = 0.003). During follow-up, sarcopenia was associated with an increased risk of hospitalization (OR 2.2 95% CI [0.9-5.0]; p = 0.07), increased number of in-hospital days (p < 0.001), and reduced survival (HR 6.7 [95% CI; 1.8-25.0]; p = 0.005)., Conclusion: Sarcopenia is a common complication of chronic pancreatitis and associates with adverse health-related outcomes. As sarcopenia is not recognized by conventional anthropometric parameters in the majority of patients, systematic nutritional assessment should be prioritized., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 IAP and EPC. All rights reserved.)

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., (Copyright © 2017 IAP and EPC. All rights reserved.)

Background/objectives: Chronic pancreatitis (CP) is a complex and debilitating disease with high resource utilisation. Prospective data on hospital admission rates and associated risk factors are scarce. We investigated hospitalisation rates, causes of hospitalisations and associated risk factors in CP outpatients., Methods: This was a prospective cohort study comprising 170 patients with CP. The primary outcome was time to first pancreatitis related hospitalisation and secondary outcomes were the annual hospitalisation frequency (hospitalisation burden) and causes of hospitalisations. A number of clinical and demographic parameters, including pain pattern and severity, opioid use and parameters related to the nutritional state, were analysed for their association with hospitalisation rates., Results: Of the 170 patients, 57 (33.5%) were hospitalised during the follow-up period (median 11.4 months [IQR 3.8-26.4]). The cumulative hospitalisation incidence was 7.6% (95% CI; 4.5-12.2) after 30 days and 28.8% (95% CI; 22.2-35.7) after 1 year. Eighteen of the hospitalised patients (32%) had three or more admissions per year. High dose opioid treatment (>100 mg per day) (Hazard Ratio 3.1 [95% CI; 1.1-8.5]; P = 0.03) and hypoalbuminemia (<36 g/l) (Hazard Ratio 3.8 [95% CI; 2.0-7.8]; P < 0.001) were identified as independent risk factors for hospitalisation. The most frequent causes of hospitalisations were pain exacerbation (40%) and common bile duct stenosis (28%)., Conclusions: One-third of CP outpatients account for the majority of hospital admissions and associated risk factors are high dose opioid treatment and hypoalbuminemia. This information should be implemented in outpatient monitoring strategies to identify risk patients and improve treatment., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)