Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis : A Sham-Controlled, Randomized Trial.

BACKGROUND: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis. OBJECTIVE: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones. DESIGN: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781). SETTING: Asian Institute of Gastroenterology in India from February 2021 to July 2022. PARTICIPANTS: 106 patients with chronic pancreatitis. INTERVENTION: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures. MEASUREMENTS: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions. RESULTS: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, -0.7 [95% CI, -1.3 to 0] on the VAS; P = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, -5.4 days [CI, -9.9 to -0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups. LIMITATION: Single-center study and limited duration of follow-up. CONCLUSION: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief. PRIMARY FUNDING SOURCE: Asian Institute of Gastroenterology and Aalborg University Hospital.

Metabolic Sequelae: The Pancreatitis Zeitgeist of the 21st Century.

Holistic management of pancreatitis means that gastroenterologists in the 21st Century should think beyond improving in-hospital outcomes of pancreatitis alone. In particular, there is considerable room for optimizing the management of new-onset diabetes, exocrine pancreatic insufficiency, and other metabolic sequelae of pancreatitis. The present article provides state-of-the-art information on classification, terminology, and burden of the common sequelae of pancreatitis. A high-risk group of patients with pancreatitis is identified, which is positioned to benefit the most from the metabolic sequelae surveillance program introduced in this article. The program involves continuous follow-up after pancreatitis diagnosis, with the focus on early identification of new-onset diabetes after pancreatitis and exocrine pancreatic insufficiency. The metabolic sequelae surveillance program is scalable and has the potential to reduce the burden of pancreatitis through tertiary prevention in the decades to come.

Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study.

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.

Surgical strategies for chronic pancreatitis in a 1,327- patient Scandinavian Baltic pancreatic Club (SBPC) register.

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.

Overlap and cumulative effects of pancreatic duct obstruction, abnormal pain processing and psychological distress on patient-reported outcomes in chronic pancreatitis.

OBJECTIVE: Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs). DESIGN: We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses. RESULTS: Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress. CONCLUSION: Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management. TRIAL REGISTRATION NUMBER: The study was registered with ClinicalTrials.gov (NCT03434392).

Pancreatic QST Differentiates Chronic Pancreatitis Patients into Distinct Pain Phenotypes Independent of Psychiatric Comorbidities.

BACKGROUND & AIMS: Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities. METHODS: A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups. RESULTS: A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P = .03) and rates of constant pain (P = .002) as well as decreased QoL (P < .001) and physical functioning (P =.03) in comparison with the other two pain phenotypes. In contrast, psychiatric comorbidities were similar across all groups. CONCLUSIONS: P-QST may serve as a novel unbiased pain assessment tool in CP as it categorizes patients into distinct pain phenotypes independent of their psychiatric comorbidities.

The spectrum of diabetes in acute and chronic pancreatitis.

PURPOSE OF REVIEW: To discuss the spectrum of diabetes related to acute and chronic pancreatitis (which are types of pancreatogenic diabetes) and its overlapping features with type 1 and type 2 diabetes. RECENT FINDINGS: Patients with diabetes related to acute and chronic pancreatitis present clinically within a spectrum of overlapping features with other forms of diabetes. In this spectrum, glucose metabolism alterations range from increased insulin resistance following acute pancreatitis (resembling type 2 diabetes) towards a permanent loss of beta-cell function and impaired insulin secretion in end-stage chronic pancreatitis. Overlapping features with type 1 diabetes (beta cell autoantibodies) and type 2 diabetes (obesity, dyslipidemia, and hereditary/genetic factors) contribute to the heterogeneity of this spectrum. SUMMARY: Pancreatogenic diabetes secondary to acute or chronic pancreatitis is a heterogeneous entity with a variable clinical presentation, including many cases that are misdiagnosed and treated as type 2 diabetes. This is problematic as pancreatogenic diabetes is associated with a poor prognosis and entails special considerations for management. Recent discoveries showing overlapping features with type 1 and type 2 diabetes along with an improved understanding of its pathophysiology are expected to improve the diagnosis and treatment of these and other forms of pancreatogenic diabetes.

Prevalence of primary painless chronic pancreatitis: A systematic review and meta-analysis.

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.

Assessment of pain associated with chronic pancreatitis: An international consensus guideline.

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.

Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

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.

Association of multiple patient and disease characteristics with the presence and type of pain in chronic pancreatitis.

BACKGROUND AND AIM: Pain is the primary symptom of chronic pancreatitis (CP) and associates with a number of patient and disease characteristics. However, the complex interrelations of these parameters are incompletely understood, and pain treatment remains unsatisfactory in a large proportion of patients. The aim of this study is to investigate multiple pain risk factors in a large population of CP patients, with a special emphasis on patients' patterns of smoking and alcohol use. METHODS: This was a multicenter, cross-sectional study including 1384 patients with CP. Patient demographics and disease characteristics, as well as current patterns of smoking and alcohol use, were compared for patients with pain (n = 801) versus without pain (n = 583). Multivariate logistic regression models were performed to assess the variables associated with the presence and type of pain (constant vs intermittent pain). RESULTS: The mean age of participants was 52.1 ± 14.6 years, and 914 (66%) were men. Active smoking (odds ratio 1.6 [95% confidence interval 1.1-2.2], P = 0.005) and alcohol consumption (odds ratio 1.8 [95% confidence interval 1.1-3.0], P = 0.03) were independently associated with the presence of pain. In addition, patients' age at diagnosis, pancreatic duct pathology, and the presence of pseudocysts, duodenal stenosis, and exocrine pancreatic insufficiency were confirmed as pain risk factors (all P ≤ 0.01). Constant pain, as opposed to intermittent pain, was more frequently reported by smokers (P = 0.03), while alcohol consumption was associated with intermittent pain (P = 0.006). CONCLUSION: Multiple patient and disease characteristics, including patterns of smoking and alcohol consumption, associate with the presence and type of pain in patients with CP.

Is Preoperative Quantitative Sensory Testing Related to Persistent Postsurgical Pain? A Systematic Literature Review.

Persistent postsurgical pain (PPSP) is a common complication of surgery that significantly affects quality of life. A better understanding of which patients are likely to develop PPSP would help to identify when perioperative and postoperative pain management may require specific attention. Quantitative sensory testing (QST) of a patient's preoperative pain perception is associated with acute postoperative pain, and acute postoperative pain is a risk factor for PPSP. The direct association between preoperative QST and PPSP has not been reviewed to date. In this systematic review, we assessed the relationship of preoperative QST to PPSP. We searched databases with components related to (1) preoperative QST; (2) association testing; and (3) PPSP. Two authors reviewed all titles and abstracts for inclusion. Inclusion criteria were as follows: (1) QST performed before surgery; (2) PPSP assessed ≥3 months postoperatively; and (3) the association between QST measures and PPSP is investigated. The search retrieved 905 articles; 24 studies with 2732 subjects met inclusion criteria. Most studies (22/24) had moderate to high risk of bias in multiple quality domains. Fourteen (58%) studies reported a significant association between preoperative QST and PPSP. Preoperative temporal summation of pain (4 studies), conditioned pain modulation (3 studies), and pressure pain threshold (3 studies) showed the most frequent association with PPSP. The strength of the association between preoperative QST and PPSP varied from weak to strong. Preoperative QST is variably associated with PPSP. Measurements related to central processing of pain may be most consistently associated with PPSP.

Fermentable Sugar Ingestion, Gas Production, and Gastrointestinal and Central Nervous System Symptoms in Patients With Functional Disorders.

BACKGROUND & AIMS: Functional gastrointestinal disorders (FGID) are defined by broad phenotypic descriptions and exclusion of recognizable disease. FGIDs cause multi-organ symptoms and abnormal results in a wide range of laboratory tests, indicating broad mechanisms of pathogenesis. Many patients with FGID develop symptoms following ingestion of fermentable sugars; we investigated the associations between symptoms and intestinal gas production following sugar provocation tests to elucidate mechanisms of FGID. METHODS: We performed fructose and lactose breath tests in 2042 patients with a diagnosis of FGID (based on Rome III criteria), referred to a gastroenterology practice from January 2008 through December 2011. Medical and diet histories were collected from all subjects. Breath samples were collected before and each hour after, for 5 hours, subjects ingested fructose (35 g) and lactose (50 g) dissolved in 300 mL water. Hydrogen and methane gas concentrations were measured and GI and non-GI symptoms were registered for 5 hours following sugar ingestion. Symptom and gas time profiles were compared, treelet transforms were used to derive data-related symptom clusters, and the symptom severity of the clusters were analyzed for their association with breath gas characteristics. RESULTS: We identified 11 GI and central nervous system (CNS) symptom profiles and hydrogen and methane breath concentrations that changed significantly with time following sugar ingestion. Treelet transform analysis identified 2 distinct clusters, based on GI and CNS symptoms. The severity scores for the GI and CNS symptoms correlated following ingestion of sugars (all, P < .0001). However, only the GI symptoms associated with hydrogen and methane gas production (all, P < .0001). CONCLUSIONS: In an analysis of breath test results from more than 2000 patients with FGIDs, we identified clusters of GI and CNS symptoms in response to fructose of lactose ingestion. The association between specific symptoms and breath gas concentrations indicate distinct mechanisms of FGID pathogenesis, such as changes in the microbiome or mechanical and chemical sensitization. ClinicalTrials.gov ID: NCT02085889.

Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP. METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol). RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046). DISCUSSION: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.

A Pragmatic Utility Function to Describe the Risk-Benefit Composite of Opioid and Nonopioid Analgesic Medication.

It is not straightforward to simultaneously evaluate the beneficial and harmful effects of pain management, since different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here, we construct "pragmatic" utility functions based on measurements of benefit and harm, but without making assumptions about the underlying pharmacokinetics and pharmacodynamics. Using data from two previous studies, utility functions were designed by estimating the probability of occurrence of benefit and harm and combining these into one function. Study 1 was a clinical trial on the effect of oral pregabalin on pain relief in chronic pancreatitis patients, with endpoint analgesia and dizziness monitored for 21 days. Study 2 was an experimental study on the effect of intravenous fentanyl on antinociception and respiratory depression in healthy volunteers. From study 1, the utility function was negative the first week of treatment, indicative of the greater probability of dizziness than analgesia, but positive thereafter. From study 2, the utility function showed a nadir 30 minutes after dosing, after which the probability function slowly increased toward zero. A pragmatic utility function based on the probability of two binary outcomes, analgesia and adverse effect, was successfully constructed using data from the two previous studies. The results yielded valuable insights into the utility of treatment and may be highly educative for physicians and potentially used in development of potent analgesics without serious side effects.

Sarcopenia associates with increased hospitalization rates and reduced survival in patients with chronic pancreatitis.

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/m2). 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.

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

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 ±â€¯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.

Symptoms of mast cell activation syndrome in functional gastrointestinal disorders.

Objectives: Mast cell involvement is evident in functional gastrointestinal disorders (FGID). FGID and mast cell activation syndrome (MCAS) are associated with multi-organ symptoms. An overlap has not been assessed.Methods: MCAS symptoms were determined by questionnaires in 2083 FGID patients.Results: The median number of MCAS symptoms ([IQR] (range 0-16)) was 6 [4-8] in all FGID, and in functional dyspepsia (FD) patients, 7 [5-9] in overlapping irritable bowel syndrome and FD (IBS+FD), 5 [3-8] in IBS and 5 [3-6] in non-IBS/non-FD (p < .001 vs. FD and IBS + FD) patients. MCAS symptoms in ≥2 organ-systems existed in 1773 (85%) of all patients.Conclusions: MCAS symptoms are common in FGID warranting further mechanistic investigation.

Development and Validation of a Chronic Pancreatitis Prognosis Score in 2 Independent Cohorts.

BACKGROUND & AIMS: The clinical course of chronic pancreatitis is unpredictable. There is no model to assess disease severity or progression or predict patient outcomes. METHODS: We performed a prospective study of 91 patients with chronic pancreatitis; data were collected from patients seen at academic centers in Europe from January 2011 through April 2014. We analyzed correlations between clinical, laboratory, and imaging data with number of hospital readmissions and in-hospital days over the next 12 months; the parameters with the highest degree of correlation were used to develop a 3-stage chronic pancreatitis prognosis score (COPPS). The predictive strength was validated in 129 independent subjects identified from 2 prospective databases. RESULTS: The mean number of hospital admissions was 1.9 (95% confidence interval [CI], 1.39-2.44) and 15.2 for hospital days (95% CI, 10.76-19.71) for the development cohort and 10.9 for the validation cohort (95% CI, 7.54-14.30) (P = .08). Based on bivariate correlations, pain (numeric rating scale), level of glycated hemoglobin A1c, level of C-reactive protein, body mass index, and platelet count were used to develop the COPPS system. The patients' median COPPS was 8.9 points (range, 5-14). The system accurately discriminated stages of disease severity (low to high): A (5-6 points), B (7-9), and C (10-15). In Pearson correlation analysis of the development cohort, the COPPS correlated with hospital admissions (0.39; P < .01) and number of hospital days (0.33; P < .01). The correlation was validated in the validation set (Pearson correlation values of 0.36 and 0.44; P < .01). COPPS did not correlate with results from the Cambridge classification system. CONCLUSIONS: We developed and validated an easy to use dynamic multivariate scoring system, similar to the Child-Pugh-Score for liver cirrhosis. The COPPS allows objective monitoring of patients with chronic pancreatitis, determining risk for readmission to hospital and potential length of hospital stay.

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.