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.

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.

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.

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations-SonoVue®, Sonazoid™, and Optison™-were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh-Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.

Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?

Autonomic neuropathy in patients with diabetes mellitus, and especially complications related to gastrointestinal neuropathy, are often overlooked in the clinic. Diabetic gastroenteropathy affects every segment of the gastrointestinal tract and generates symptoms that may include nausea, early satiety, vomiting, abdominal pain, constipation, and diarrhea. Severe cases can be complicated by weight loss, dehydration, and electrolyte disturbances. The pathophysiology is complex, the diagnostics and treatment options are multidisciplinary, and there is generally a lack of evidence for the treatment options. The aims for this review are first to summarize the pathophysiology and describe possible and expected symptoms and complications.Further, we will try to supply the clinician with a straightforward tool for diagnostics, and then, we shall summarize established treatment options, including diet recommendations, pharmacological and non-pharmacological options. Finally, we will explore the multiple possibilities of novel treatment, looking at medications related to the pathophysiology of neuropathy, other manifestations of autonomic neuropathies, and symptomatic treatment for other gastrointestinal disorders, also including new knowledge of endosurgical and neuromodulatory treatment. The overall goal is to increase awareness and knowledge on this frequent diabetic complication and to provide better tools for diagnosis and treatment. Ultimately, we hope to encourage further research in this field, as there are clear shortcomings in terms of biomarkers, pathophysiology, as well as treatment possibilities. In conclusion, diagnosis and management of diabetic gastroenteropathy are challenging and often require multidisciplinary teams and multimodal therapies. Treatment options are sparse, but new pharmacological, endoscopic, and neuromodulatory techniques have shown promising results in initial studies.

Gastric function in diabetic gastroparesis assessed by ultrasound and scintigraphy.

BACKGROUND: Gastroparesis is a severe diabetes complication characterized by delayed gastric emptying. We examined patients with symptoms of diabetic gastroparesis using gastric emptying scintigraphy and ultrasound drink test. The primary aim was to investigate how ultrasound could provide information about gastric motility features in diabetic gastroparesis. MATERIAL AND METHODS: We prospectively included 58 patients with diabetes (48 type 1) with symptoms of gastroparesis and 30 healthy controls. Patients were examined with ultrasound of the stomach in a seated position after drinking 500 ml low-caloric meat soup, at the same time recording dyspeptic symptoms. The following day, they were examined with gastric emptying scintigraphy, defining gastroparesis as >10% retention after 4 h. KEY RESULTS: We found motility disturbances in the proximal stomach measured by ultrasound in patients with diabetic gastroparesis. A linear mixed effects model including repeated ultrasound measurements revealed a slower decrease of the proximal stomach size in gastroparesis compared to healthy controls (p < 0.01), and the proximal diameter at 20 min was correlated to scintigraphy at 4 h (r = 0.510, p = 0.001). The antrum in patients with diabetic gastroparesis was twice as large compared to healthy controls (p = 0.009), and fasting antral size was correlated to gastric emptying scintigraphy (r = 0.329, p = 0.013). Both diabetes patients with and without gastroparesis had impaired accommodation (p = 0.011). CONCLUSIONS AND INFERENCES: On ultrasound, we found delayed reduction of proximal stomach size and impaired accommodation after a liquid meal in patients with gastroparesis, emphasizing the role of the proximal stomach. Furthermore, we found antral distention in gastroparesis patients.

Gastrointestinal transit and contractility in diabetic constipation: A wireless motility capsule study on diabetes patients and healthy controls.

BACKGROUND: Diabetic constipation is traditionally attributed to slow colonic transit, despite limited evidence. More than half of patients find treatment unsatisfactory. To improve treatment, there is a need for better diagnostic understanding of the condition. OBJECTIVE: In this wireless motility capsule study, we aimed to investigate gastrointestinal transit and contractility in diabetes patients with and without constipation, and in healthy controls. METHODS: We prospectively included type 1 or type 2 diabetes patients with gastrointestinal symptoms. Based on the Gastrointestinal Symptom Rating Scale we distinguished into two groups: with constipation and without constipation. Non-diabetic controls were asymptomatic. All were examined with wireless motility capsule, determining transit times and contractility parameters. RESULTS: 57 patients (42 women, 46 with type 1 diabetes) and 26 healthy controls (14 women) were included. We found no difference in transit times between diabetes patients with and without constipation. Compared to healthy controls (35:55, h:min), whole-gut transit was slower in both diabetes patients with constipation (66:15, p = 0.03) and without constipation (71:16, p < 0.001). Small bowel motility index correlated rs  = -0.32 (p = 0.01) with constipation symptoms. CONCLUSIONS: Diabetes patients with constipation had similar transit times as those without constipation. Both groups had slower whole-gut transit than healthy controls. Constipation was associated with reduced small bowel, but not colonic contractility. Our results imply that other mechanisms than slow colonic transit may be more important in the pathogenesis of diabetic constipation.

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.

Diabetic diarrhoea: A study on gastrointestinal motility, pH levels and autonomic function.

BACKGROUND: Chronic diarrhoea is a common, but poorly investigated diabetes complication. Autonomic neuropathy is a leading pathophysiological theory founded on old, small studies. Studies of gastrointestinal motility and pH levels are lacking. OBJECTIVES: Using new diagnostic methods, we aimed to find out if diabetic diarrhoea was associated with alterations in gastrointestinal motility, pH levels and autonomic function. METHODS: Fifty-seven patients (42 women, 46 with type 1 diabetes) were prospectively included. Symptoms were evaluated with the gastrointestinal symptom rating scale, defining ≥4 points as cases with diarrhoea. Patients scoring <4 were used as controls. We used the wireless motility capsule to measure gastrointestinal transit times, pH levels and contractility parameters. Autonomic function was assessed by measuring heart rate variability, baroreflex sensitivity and orthostatic hypotension. RESULTS: Seventeen patients (30%) had diarrhoea. Compared with controls, cases had slower gastric emptying (21:46 vs. 4:14, h:min, p = 0.03) and faster colonic transit (18:37 vs. 54:25, p < 0.001). Cases had increased intraluminal pH in the antrum (2.4 vs. 1.2, p = 0.009), caecum (7.3 vs. 6.4, p = 0.008) and entire colon (7.1 vs. 6.7, p = 0.05). They also had a decreased pH difference across the pylorus (3.3 vs. 4.9, p = 0.004) and ileocaecal junction (0.6 vs 1.0, p = 0.009). The groups did not differ in autonomic function, but diastolic blood pressure drop correlated rs = -0.34 (p = 0.04) with colonic transit time. CONCLUSIONS: Patients with diabetic diarrhoea had altered gastrointestinal transit and intraluminal pH levels, but minimal changes in autonomic function. Our results suggest that tests of gastrointestinal function are clinically useful in diabetic diarrhoea.

Gastroparesis Symptoms Associated with Intestinal Hypomotility: An Explorative Study Using Wireless Motility Capsule.

OBJECTIVE: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. PATIENTS AND METHODS: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). RESULTS: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (rs = -0.31, p = 0.007), small bowel (rs = -0.41, p < 0.001) and colonic (rs = -0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (rs = -0.81, p < 0.001) and mean stomach pressure (rs = -0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (rs = -0.77, p < 0.001) and colon (rs = -0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (rs = -0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (rs = -0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. CONCLUSION: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.

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.

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.

Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis.

BACKGROUND: Gastroparesis is a potentially severe late complication of diabetes mellitus. Today, delayed gastric emptying (GE) is mandatory for establishing the diagnosis. In this study, we compared wireless motility capsule (WMC) with gastric emptying scintigraphy (GES). METHODS: Seventy-two patients (49 women) with diabetes mellitus (59 type 1) and symptoms compatible with gastroparesis were prospectively included between 2014 and 2018. Patients were simultaneously examined with GES and WMC. Symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) questionnaire. All patients were on intravenous glucose-insulin infusion during testing. KEY RESULTS: WMC and GES correlated r = .74, P < .001. Compared to GES, WMC at ordinary cutoff for delayed GE (300 minutes) had a sensitivity of 0.92, specificity 0.73, accuracy 0.80, and Cohen's kappa κ = 0.61 (P < .001). By receiver operating characteristics (ROC), the area under the curve was 0.95 (P < .001). A cutoff value for delayed GE of 385 minutes produced sensitivity 0.92, specificity 0.83, accuracy 0.86, and Cohen's kappa κ = 0.72 (P < .001). Inter-rater reliability for GE time with WMC was r = .996, κ = 0.97, both P < .001. There was no difference in symptom severity between patients with normal and delayed GE. CONCLUSIONS & INFERENCES: Our findings demonstrate the applicability of WMC as a reliable test to assess gastric emptying in diabetic gastroparesis showing very high inter-observer correlation. By elevating the cutoff value for delayed emptying from 300 to 385 minutes, we found higher specificity without reducing sensitivity.

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.