Quality of life after endoscopic procedures for chronic pancreatitis: A multicentre study.

BACKGROUND: Chronic Pancreatitis (CP) causes morphological changes in the pancreatic tissue, leading to complications and pain, which may require endoscopic interventions. OBJECTIVE: Our aim was to determine the frequency of endoscopic procedures (EP) in CP patients and to analyse pain and quality of life (QoL) in these patients after their EP. METHODS: This study included 1327 CP patients from the Scandinavian Baltic Pancreatic Club (SBPC) database including four countries and eight centres. We analysed patients undergoing EPs and gathered information on the EP, pancreatic function, pain, disease and duration. The EORTC C-30 QoL questionnaire was gathered prospectively and multivariable analysis was conducted on independent parameters between the groups. The reference population had no interventions (n = 870). RESULTS: 260 CP patients (22%) underwent EPs, median one year (range 0-39 years) after CP diagnosis. 68% were males. The median age was 59 (20-90) years. Most common aetiological factors were alcohol in 65% and smoking in 71%. Extracorporeal shock wave lithotripsy (ESWL) was used in 6% of the CP population and in 21% of the EP group. Biliary duct stenting was performed on 37% and pancreatic stenting was performed on 56% of the patients. There was no difference in pain patterns between patients who had pancreatic stenting and the reference population. The EP group had slightly better QoL (p = 0.047), functioning and fewer symptoms than the reference population, in the multivariable analysis there was no interaction effect analysis between the groups. The pancreatic stent group had better QoL and the same amount of pain than the reference group. The patients who needed later surgery (23%) had more pain (p = 0.043) and fatigue (p = 0.021). CONCLUSIONS: One in five of the CP patients underwent EP. These patients scored higher on QoL responses and had better symptom scores. CP patients who had pancreatic stenting performed had the same pain patterns as the reference population. Randomised prospective trials are needed to determine the effect of endoscopy procedures on CP patients.

Inter- and intra-observer variability of computed tomography-based parenchymal- and ductal diameters in chronic pancreatitis: a multi-observer international study.

PURPOSE: The need for incorporation of quantitative imaging biomarkers of pancreatic parenchymal and ductal structures has been highlighted in recent proposals for new scoring systems in chronic pancreatitis (CP). To quantify inter- and intra-observer variability in CT-based measurements of ductal- and gland diameters in CP patients. MATERIALS AND METHODS: Prospectively acquired pancreatic CT examinations from 50 CP patients were reviewed by 12 radiologists and four pancreatologists from 10 institutions. Assessment entailed measuring maximum diameter in the axial plane of four structures: (1) pancreatic head (PDhead), (2) pancreatic body (PDbody), (3) main pancreatic duct in the pancreatic head (MPDhead), and (4) body (MPDbody). Agreement was assessed by the 95% limits of agreement with the mean (LOAM), representing how much a single measurement for a specific subject may plausibly deviate from the mean of all measurements on the specific subject. Bland-Altman limits of agreement (LoA) were generated for intra-observer pairs. RESULTS: The 16 observers completed 6400 caliper placements comprising a first and second measurement session. The widest inter-observer LOAM was seen with PDhead (± 9.1 mm), followed by PDbody (± 5.1 mm), MPDhead (± 3.2 mm), and MPDbody (± 2.6 mm), whereas the mean intra-observer LoA width was ± 7.3, ± 5.1, ± 3.7, and ± 2.4 mm, respectively. CONCLUSION: Substantial intra- and inter-observer variability was observed in pancreatic two-point measurements. This was especially pronounced for parenchymal and duct diameters of the pancreatic head. These findings challenge the implementation of two-point measurements as the foundation for quantitative imaging scoring systems in CP.

Pancreatic enzyme treatment in chronic pancreatitis: Quality of management and adherence to guidelines-A cross-sectional observational study.

OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication in patients with chronic pancreatitis (CP), leading to increased morbidity and mortality if not treated adequately. Pancreatic enzyme replacement therapy|pancreas enzyme replacement therapy (PERT) is the cornerstone in treatment of patients with PEI. In the present study, we use data from the Scandinavian Baltic Pancreatic Club database to examine adherence of PERT according to United European Gastroenterology evidence-based guidelines treatment of CP. PATIENTS AND METHODS: Patients with definitive or probable CP according to M-ANNHEIM diagnostic criteria were included. We collected information on exposures, exocrine function, intake of pancreatic enzymes, and markers of nutrition. Fecal elastase <200 µg/g was defined as a marker for PEI. Enzyme replacement therapy of 100,000 lipase units or more was defined as adequate treatment. RESULTS: We included 1006 patients from 8 centers in five countries. Sixty-four percent of the patients were correctly treated. Twenty-five per cent of PEI patients were not taking enzymes at all, and 20% of PEI patients were undertreated with insufficient PERT doses according to the guidelines. Fourteen percent of patients with sufficient pancreatic function were receiving enzymes despite normal exocrine pancreatic function. There were center differences. Current smoking was associated with lack of treatment and alcohol abuse was associated with under-treatment. There were no associations between "no treatment" or "under-treatment" for underweight or vitamin D deficiency. CONCLUSION: In our CP expert centers, the adherence to guidelines for enzyme treatment is insufficient. Both patient factors and center differences have influence on treatment adherence.

Structural imaging findings are related to clinical complications in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Structural pancreatic changes and complications related to chronic pancreatitis are well described, but little is known about their relationship. We aimed to explore the associations between pancreatic morphology and clinical complications in a large chronic pancreatitis cohort. METHODS: The Scandinavian Baltic Pancreatic Club database collects registrations on patients with definite or probable chronic pancreatitis according to the M-ANNHEIM diagnostic criteria. In this cross-sectional study, we used multivariate logistic regression analyses to evaluate whether imaging-based structural pancreatic changes were associated with common clinical complications. We adjusted for sex, age, disease duration, current alcohol abuse and current smoking. RESULTS: We included 742 patients with a mean age of 55 years. Among these, 68% were males, 69% had pancreatic exocrine insufficiency, 35% had diabetes, 12% were underweighted and 68% reported abdominal pain. Main pancreatic duct obstruction, severe (i.e. more than 14) calcifications, pancreatic atrophy and parenchymal changes throughout the entire pancreas (continuous organ involvement) were positively associated with pancreatic exocrine insufficiency. Continuous organ involvement and pseudocysts were positively and negatively associated with diabetes, respectively. Pancreatic atrophy and severe calcifications were positively associated with underweight, and severe calcifications were negatively associated with pain. CONCLUSIONS: This study shows independent associations between distinct structural changes on pancreatic imaging and clinical complications in chronic pancreatitis. Pancreatic atrophy, severe calcifications and continuous organ involvement may be of particular clinical relevance, and these findings should motivate monitoring of pancreatic function and nutritional status.

Exocrine pancreas insufficiency in chronic pancreatitis - Risk factors and associations with complications. A multicentre study of 1869 patients.

BACKGROUND/OBJECTIVES: There is scarce information about risk factors for exocrine pancreas insufficiency (EPI) in chronic pancreatitis (CP), and how it associates with other complications. The aim of the present study was to examine risk factors for EPI and associations to procedures and other CP related complications in a large, Northern European cohort. PATIENTS AND METHODS: We retrieved cross-sectional data on demographics, status on EPI, aetiological risk factors for CP, CP related complications as well as surgical and endoscopic treatment from the Scandinavian Baltic Pancreatic Club Database. Associations were assessed by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: We included 1869 patients with probable or definitive CP in the study. Exocrine pancreas insufficiency was present in 849 (45.4%) of patients. In multivariate analyses, EPI associated with smoking aetiology (OR 1.47 (1.20-1.79), p < 0.001), and nutritional/metabolic aetiology (OR 0.52 (0.31-0.87), p = 0.01) to CP. Pancreatic or common bile duct stenting procedure and pancreatic resection were both associated with EPI (ORs 1.44 (1.15-1.80), p = 0.002 and 1.54 (1.02-2.33), p = 0.04, respectively). The presence of diabetes mellitus (OR 2.45 (1.92-3.15), p < 0.001), bile duct stenosis (OR 1.48 (1.09-2.00), p = 0.02) and underweight (2.05 (OR 1.40-3.02), p < 0.001) were all associated with presence of EPI. CONCLUSIONS: Smoking, bile duct stenosis, previous stenting and resection procedures are all associated with EPI in patients with CP. Presence of EPI were also associated with malnutrition and diabetes mellitus. Hence, intensive nutritional surveillance is needed in these patients.

KRAS mutation analysis by droplet digital PCR of duodenal juice from patients with MODY8 and other pancreatic diseases.

BACKGROUND: Maturity-onset diabetes of the young type 8 (MODY8 or CEL-MODY) is an inherited pancreatic disease characterized by chronic inflammation of the pancreas and diabetes. It is not known whether MODY8 patients have increased risk for developing pancreatic cancer. We investigated KRAS mutation load in duodenal juice from MODY8 patients, comparing with other groups of pancreatic disease. METHODS: Droplet digital PCR (ddPCR) was used to detect KRAS codon 12/13/61 mutations in duodenal juice sampled from 11 MODY8 patients, nine healthy subjects and 100 patients clinically investigated due to suspected pancreatic disease. RESULTS: KRAS mutations were detected in 4/11 patients with MODY8 (36%), 1/9 healthy subjects (11%), 15/44 patients with chronic pancreatitis (CP, 34%), 3/5 patients with pancreatic ductal adenocarcinoma (PDAC, 60%), 3/20 patients with acute pancreatitis (15%), 0/13 patients with other pancreatic disorders and 2/18 patients with nonpancreatic gastrointestinal disease (11%). Of the 28 positive juice samples, 25 (89%) had low-abundance mutations in codons 12/13, with a variant allele frequency (VAF) less than 1%. KRAS-positive patients with MODY8 or CP had significantly lower VAFs than patients with PDAC (Mann-Whitney U test; p = 0.041). Although the overall mutation detection rate was higher for subjects ≥50 years old (26%) than for younger subjects (15%), the difference was not statistically significant. CONCLUSIONS: KRAS mutations were detectable in duodenal juice from MODY8 patients, but with low abundance and at the same frequency as in CP patients. The discriminative value of the analysis with regard to other pancreatic disease was limited.

Pancreatic exocrine insufficiency in diabetes is associated with autonomic dysfunction.

OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is prevalent in diabetes. Pathophysiological theories imply autoimmune destruction, lack of trophic effects of insulin or impaired neuronal stimulation, but the relationship between PEI and autonomic dysfunction is largely unknown. In a pilot study, we aimed to investigate if patients with diabetes and PEI had impaired autonomic function. METHODS: We measured faecal elastase in 59 patients with type 1 or 2 diabetes, using a cut-off-value <200 µg/g to define PEI. Based on faecal elastase results, patients were stratified into matched case (n = 8) and control groups (n = 13). We used heart rate variability, baroreflex sensitivity and orthostatic hypotension tests to assess autonomic dysfunction. RESULTS: All baroreflex sensitivity parameters were reduced in cases with PEI compared with controls (all p < .05). The heart rate variability parameters root mean square of successive RR interval differences (p = .05) and high frequency (p = .04) were also reduced. We found no difference in orthostatic hypotension between the groups. CONCLUSIONS: In this first-of-its-kind study, we found that diabetes patients with PEI had reduced autonomic function compared with matched controls. Although numbers are small, results support the hypothesis that autonomic dysfunction could be a contributor to PEI in diabetes.

Diagnostic Accuracy of Transabdominal Ultrasound and Computed Tomography in Chronic Pancreatitis: A Head-to-Head Comparison.

Purpose Computed tomography (CT) is the most used imaging modality for diagnosing chronic pancreatitis (CP), but advances in transabdominal ultrasound (US) technology have given US a position as a viable alternative. We aimed to evaluate the diagnostic accuracy of abdominal CT and pancreatic US compared to the reference standard, a modified Mayo score. Materials and Methods CT, US, and endoscopic ultrasound (EUS) were performed in patients referred due to suspected CP. The modified Mayo score included EUS results, clinical presentation, and results from exocrine and endocrine pancreatic function tests. We scored CT findings according to the modified Cambridge classification and US findings according to the Rosemont classification. Results In total, 73 patients were included. 53 patients (73%) were categorized as CP and 20 (27%) as non-CP. CT and US yielded similar sensitivities (68% and 64%, respectively) and specificities (75 and 85%, respectively) and similar areas under the receiver operating characteristic curves for diagnosing CP. We found no significant differences between the areas under the receiver operating characteristic curves (AUROCs) for CT (AUROC 0.75, 95% CI 0.63-0.87) and US (AUROC 0.81, 95% CI 0.71-0.91). Conclusion We conclude that CT and US had comparable, moderate accuracy in diagnosing CP. Neither modality had high enough sensitivity to exclude the diagnosis as a standalone method.

Diagnostic Accuracy of Computed Tomography Scores in Chronic Pancreatitis.

OBJECTIVES: Computed tomography (CT) is the most commonly used imaging modality when diagnosing chronic pancreatitis (CP). We aimed to evaluate the diagnostic accuracy of CT scores for diagnosing CP. METHODS: One hundred eighteen patients were retrospectively included from an observational cohort study that comprised patients referred because of suspected CP. Patients were categorized as CP or non-CP using a modified Mayo score based on biochemistry, clinical presentation, and findings on endoscopic ultrasound and/or transabdominal ultrasound. The CT scans were scored according to the modified Cambridge classification and the unweighted CT score. Diagnostic performance indices were calculated using the modified Mayo score as reference standard. RESULTS: Seventy-six of the 118 patients fulfilled the CP diagnostic criteria (Mayo score ≥4). The modified Cambridge classification and the unweighted CT score yielded sensitivities of 63% and 67% and specificities of 91% and 91%, respectively, and similar areas under the receiver operating characteristic curves (95% confidence interval) of 0.79 (0.71-0.88)/0.81 (0.73-0.89), respectively (P, not significant). CONCLUSIONS: Both CT scores had similar, moderate accuracies for diagnosing CP. The limitation in diagnostic accuracy makes CT ineligible as a single method to diagnose CP, supporting that the diagnostic process for CP needs to incorporate other imaging methods and/or markers for better diagnostics.

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database.

OBJECTIVES: The relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP. METHODS: Subjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features. RESULTS: We included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]). CONCLUSION: In this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.

Protein misfolding in combination with other risk factors in CEL-HYB1-mediated chronic pancreatitis.

OBJECTIVES: The hybrid allele of the carboxyl ester lipase gene (CEL-HYB1) is a genetic risk factor for chronic pancreatitis (CP) although the mechanism promoting disease development is largely unknown. Here, we aimed to clinically describe subjects carrying the CEL-HYB1 allele and to elucidate why the protein product is pathogenic by analyzing pancreatic secretions and cellular models. METHODS: Norwegian cases (n = 154) diagnosed with recurrent acute pancreatitis or CP were subjected to genetic screening by a CEL-HYB1-specific PCR assay followed by Sanger sequencing. For investigation of CEL-HYB1 protein secretion, duodenal juice samples from cases and controls were analyzed by western blotting. HEK293cells were transfected with constructs expressing CEL-HYB1 or the normal CEL protein (CEL-WT) and analyzed by qPCR, cell fractionation and western blotting. RESULTS: Two CEL-HYB1-positive families were identified. In both pedigrees, CEL-HYB1 did not fully co-segregate with disease. One proband had recurrent acute pancreatitis and was an active smoker. Her mother was a CEL-HYB1 carrier who had suffered from several attacks of acute pancreatitis until she stopped smoking. The other proband was diagnosed with CP and pancreas divisum. Her CEL-HYB1-positive parent was symptom-free but exhibited pancreatic imaging changes. When analyzing the CEL protein in duodenal juice, CEL-WT was readily detectable but no band corresponding to the risk variant was seen. In CEL-HYB1-transfected cells, we observed impaired protein secretion, protein aggregation and endoplasmic reticulum stress. CONCLUSION: Our data suggest that CEL-HYB1, in combination with well-known pancreatitis risk factors, causes disease through the misfolding-dependent pathway of genetic CP risk.

Patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Smoking and alcohol abuse are established risk factors for chronic pancreatitis (CP). Few studies have examined how exposure to smoking and alcohol abuse act as risk factors for complications in CP. Our aim was to examine associations between patient reported exposure to smoking and alcohol abuse and complications in CP in a large cohort of patients from the Scandinavian and Baltic countries. METHODS: We retrieved data on demographics, CP related complications and patients' histories of exposure to smoking and alcohol abuse from the Scandinavian Baltic Pancreatic Club database. Associations were investigated by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: A complete history of smoking and alcohol exposure was available for 932 patients. In multivariate regression analyses, the presence of pain and exocrine pancreatic insufficiency were both significantly associated with history of smoking (OR 1.94 (1.40-2.68), p < 0.001 and OR 1.89 (1.36-2.62), p < 0.001, respectively) and alcohol abuse (OR 1.66 (1.21-2.26), p = 0.001 and 1.55 (1.14-2.11), p = 0.005, respectively). Smoking was associated with calcifications (OR 2.89 (2.09-3.96), p < 0.001), moderate to severe ductal changes (OR 1.42 (1.05-1.92), p = 0.02), and underweight (OR 4.73 (2.23-10.02), p < 0.001). History of alcohol abuse was associated with pseudocysts (OR 1.38 (1.00-1.90) p = 0.05) and diabetes mellitus (OR 1.44 (1.03-2.01), p = 0.03). There were significantly increased odds-ratios for several complications with increasing exposure to smoking and alcohol abuse. CONCLUSION: Smoking and alcohol abuse are both independently associated with development of complications in patients with CP. There seems to be a dose-dependent relationship between smoking and alcohol abuse and complications in CP.

A young male with epitheliolysis in the small bowel and colon.

Background: Toxic epidermal necrolysis (TEN) is characterized by epidermal necrosis of various degree, and can affect the entire body surface. Affection of small bowel and colon is a rare manifestation of TEN. We present a case with an unusual appearance of epitheliolysis of the small bowel and colon due to a toxic reaction.Case report: A 19 year old male was diagnosed with ulcerative colitis (UC) after treatment with tetracyclines followed by isotretinoin due to acne vulgaris. Medical treatment did not lead to improvement of his UC, and an emergency resection of the colon was performed. Postoperatively his condition worsened due to small bowel epitheliolysis, and he recovered finally 6 months later after a partial small bowel resection.Conclusion: The true cause of this very serious situation with severe gastrointestinal involvement is not fully understood. In this case, successive treatment with antibiotics and isotretinoin given to a patient with an inflamed colon might have triggered the destruction of the epithelial barrier, leading to an immense immunological reaction in the intestinal wall. We suggest that physicians should be aware of UC-like symptoms occurring prior to or during treatment with tetracyclines and/or isotretinoin.

Secretin-Stimulated Magnetic Resonance Imaging Reveals Variable Diagnostic Accuracy According to Etiology in Pancreatic Disease.

OBJECTIVES: Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic exocrine secretion. In this prospective observational study, we compare the diagnostic accuracy of s-MRI for exocrine pancreatic failure due to different pancreatic diseases and healthy controls. METHODS: We performed s-MRI in 21 cystic fibrosis (CF) patients, 78 patients with chronic pancreatitis (CP) and 20 healthy controls. Exocrine failure was defined by fecal elastase-1 of less than 200 µg/g or bicarbonate concentration from endoscopic secretin test of less than 80 mmol/L. RESULTS: Eleven CF and 61 CP patients were exocrine insufficient. Insufficient CF patients had lower s-MRI volume output compared with all other groups (P < 0.05). Insufficient CP patients had reduced volume output compared with controls and sufficient CF (P < 0.05). Secretin-stimulated MRI yielded overall accuracy of 0.78 (95% confidence interval [CI], 0.70-0.86) for exocrine failure. When divided according to etiology, the test yielded accuracy of 0.95 (95% CI, 0.90-1) in CF and 0.73 (95% CI, 0.64-0.82) in CP. CONCLUSIONS: The accuracy of s-MRI volume output measures to diagnose exocrine failure was higher in CF than in CP. Differences in s-MRI volume output in patients with exocrine failure may be due to different etiological and pathogenic mechanisms in CF and CP.

Multiple risk factors for diabetes mellitus in patients with chronic pancreatitis: A multicentre study of 1117 cases.

BACKGROUND: Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis. METHODS: We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes. RESULTS: The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all p ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all p ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes (p = 0.07). CONCLUSION: In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.

Systematic approach for assessment of imaging features in chronic pancreatitis: a feasibility and validation study from the Scandinavian Baltic Pancreatic Club (SBPC) database.

PURPOSE: There is an unmet need for new systems with quantitative pancreatic imaging assessments to support better diagnosis and understand development of chronic pancreatitis (CP). The aims were to present such an approach for assessment of imaging features in CP, to apply this system in a multi-center cohort of CP patients (feasibility study), and to report inter-reader agreement between expert radiologists (validation study). METHODS: The feasibility study included pancreatic computed tomography (CT) or magnetic resonance imaging (MRI) from 496 patients with definitive CP in the Scandinavian Baltic Pancreatic Club (SBPC) database. Images were assessed according to the new SBPC imaging system (quantitative assessments of ductal and parenchymal features). Inter-reader agreement of reported imaging parameters was investigated for 80 CT and 80 MRI examinations by two expert radiologists. RESULTS: Reporting of the imaging features into the imaging system was deemed feasible for > 80% of CT and > 90% of MRI examinations. Quantitative assessments of main pancreatic duct diameters, presence/number/diameter of calcifications, and gland diameters had high levels of inter-reader agreement with κ-values of 0.75-0.87 and intraclass correlation coefficients of 0.74-0.97. The more subjective assessments, e.g., irregular main pancreatic duct and dilated side-ducts, had poor to moderate agreement with κ-values of 0.03-0.44. CONCLUSION: The presented system provides a feasible mean for systematic assessment of CP imaging features. Imaging parameters based on quantitative assessment, as opposed to subjective assessments, have better reproducibility and should be preferred in the development of new grading systems for understanding pathophysiology and disease progression in CP.

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.

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.

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.