Trond Engjom

Quantification of pancreatic function using a clinically feasible short endoscopic secretin test.

Objectives Clinical and morphological criteria are not precise enough to diagnose early chronic pancreatitis (CP). We investigated if short endoscopic pancreas function testing as a part of routine upper endoscopy could improve clinical diagnostics. Methods Patients with suspected CP underwent modified secretin-stimulated upper endoscopy (short endoscopic secretin test, or EST). Duodenal juice was collected during 15 minutes starting 30 minutes after stimulation. A modified scoring system for CP after Layer with bicarbonate and fecal elastase 1 (FE1) was used. We tested with receiver operating characteristic curves the diagnostic accuracy of bicarbonate and FE1 and with analysis of variance how precise the 2 parameters can discriminate the groups. Results Fifty-two patients aged 19 to 67 years and 25 healthy controls aged 19 to 64 years were included. Twenty-four patients fulfilled the modified Layer Score for CP or non-CP. The overall accuracy of the EST versus FE1 test was 85%/71%, with positive and negative predictive values of 100%/79% and 80%/69%, respectively. Conclusions Short EST is rapid and easy to perform and can be incorporated in daily routines. We demonstrate that EST is superior to FE1 in the assessment of pancreatic insufficiency and may prove to be useful in diagnosing early or mild CP.

Exocrine pancreatic function in hepatocyte nuclear factor 1β‐maturity‐onset diabetes of the young (HNF1B‐MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas

To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene (HNF1B) mutation by direct testing.

Severe pancreatic dysfunction but compensated nutritional status in monogenic pancreatic disease caused by carboxyl-ester lipase mutations.

Objectives The impact of pancreatic dysfunction in several diseases of the pancreas, including chronic pancreatitis and cystic fibrosis, is obscured by concomitant extra-pancreatic disease. Carboxyl-ester lipase–maturity-onset diabetes in the young (CEL-MODY) is a monogenic, highly penetrant and progressive pancreatic disease with no known primary extrapancreatic manifestations. It is characterized by low fecal elastase, steatorrhea, and development of diabetes mellitus. We sought to determine the nature of the exocrine dysfunction in CEL-MODY and relate the findings to clinical parameters of malnutrition. Methods We examined CEL-MODY patients and control subjects by rapid, endoscopic secretin test and dynamic magnetic resonance imaging of the pancreas. The findings were related to the subjects’ clinical status. Results The CEL-MODY patients displayed severely reduced acinar function and moderately reduced ductal function of the pancreas compared with control subjects. Surprisingly, CEL-MODY patients did not have clinical or biochemical signs of malnutrition, except for subnormal levels of vitamin E. Vitamin E levels seemed to be directly related to pancreatic acinar function. Conclusions Pancreatic exocrine dysfunction in CEL-MODY is associated with severely reduced acinar and moderately reduced ductal dysfunction. Despite severely reduced exocrine pancreatic function, CEL-MODY patients revealed only minor signs of malnutrition.

Diagnostic Accuracy of a Short Endoscopic Secretin Test in Patients With Cystic Fibrosis

Objective Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF). Methods Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3− concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase. Results Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P < 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P < 0.001). Conclusions Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test.

Diagnostic accuracy of secretin-stimulated ultrasonography of the pancreas assessing exocrine pancreatic failure in cystic fibrosis and chronic pancreatitis

Abstract Objective. Volume output failure is a feature of decreasing exocrine pancreatic function. This parameter is assessed by secretin-stimulated MRI in several studies. Our purpose was to evaluate ultrasonography of the fluid in the descending duodenum and Wirsung duct (WD) after secretin stimulation as a measure of pancreatic fluid flow in patients expected to have severe output failure. Material and methods. We included subjects with chronic pancreatitis (CP), cystic fibrosis (CF) and a group of healthy controls in a prospective observation study. Transabdominal ultrasonography was performed before and during 15 min after secretin i.v. duodenal juice was collected by endoscopic short test (EST), and bicarbonate concentration measured. Patient groups were classified according to exocrine pancreatic function. Results. Pancreatic insufficient CF (CFI) patients and CP insufficient (CPI) patients showed less duodenal fluid filling compared to other groups (p < 0.001). Measures of the WD diameter could only identify the most severe failure in the CFI group (p < 0.001). Conclusion. Secretin-stimulated ultrasonography can be used to assess pancreatic fluid flow and may be combined with EST in the evaluation of exocrine pancreatic function. Fluid filling in the descending part of duodenum was the most accurate predictor of pancreatic insufficiency in both patient groups. The test demonstrated better diagnostic accuracy diagnosing exocrine pancreatic failure in the CF patients than in CP patients.

Ultrasound echo-intensity predicts severe pancreatic affection in cystic fibrosis patients.

Background Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype. Methods Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria. Results We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p<0.001). Ductal and parenchymal changes were not prevalent in any of the groups. Conclusion The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype.

Semi-automatic motion compensation of contrast-enhanced ultrasound images from abdominal organs for perfusion analysis

This paper presents a system for correcting motion influences in time-dependent 2D contrast-enhanced ultrasound (CEUS) images to assess tissue perfusion characteristics. The system consists of a semi-automatic frame selection method to find images with out-of-plane motion as well as a method for automatic motion compensation. Translational and non-rigid motion compensation is applied by introducing a temporal continuity assumption. A study consisting of 40 clinical datasets was conducted to compare the perfusion with simulated perfusion using pharmacokinetic modeling. Overall, the proposed approach decreased the mean average difference between the measured perfusion and the pharmacokinetic model estimation. It was non-inferior for three out of four patient cohorts to a manual approach and reduced the analysis time by 41% compared to manual processing.

Interobserver Variation of the Bolus-and-Burst Method for Pancreatic Perfusion with Dynamic – Contrast-Enhanced Ultrasound

PURPOSE Dynamic contrast-enhanced ultrasound (DCE-US) can be used for calculating organ perfusion. By combining bolus injection with burst replenishment, the actual mean transit time (MTT) can be estimated. Blood volume (BV) can be obtained by scaling the data to a vessel on the imaging plane. The study aim was to test interobserver agreement for repeated recordings using the same ultrasound scanner and agreement between results on two different scanner systems. MATERIALS AND METHODS Ten patients under evaluation for exocrine pancreatic failure were included. Each patient was scanned two times on a GE Logiq E9 scanner, by two different observers, and once on a Philips IU22 scanner, after a bolus of 1.5 ml Sonovue. A 60-second recording of contrast enhancement was performed before the burst and the scan continued for another 30 s for reperfusion. We performed data analysis using MATLAB-based DCE-US software. An artery in the same depth as the region of interest (ROI) was used for scaling. The measurements were compared using the intraclass correlation coefficient (ICC) and Bland Altman plots. RESULTS The interobserver agreement on the Logiq E9 for MTT (ICC=0.83, confidence interval (CI) 0.46-0.96) was excellent. There was poor agreement for MTT between the Logiq E9 and the IU22 (ICC=-0.084, CI -0.68-0.58). The interobserver agreement for blood volume measurements was excellent on the Logiq E9 (ICC=0.9286, CI 0.7250-0.98) and between scanners (ICC=0.86, CI=0.50-0.97). CONCLUSION Interobserver agreement was excellent using the same scanner for both parameters and between scanners for BV, but the comparison between two scanners did not yield acceptable agreement for MTT. This was probably due to incomplete bursting of bubbles in some of the recordings on the IU22.

The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort

Abstract Objectives: Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. Methods: Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. Results: The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48–67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. Conclusion: The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.

Fecal fat analyses in chronic pancreatitis importance of fat ingestion before stool collection

Objective Quantitative determination of fecal fat still is the gold standard for measuring malabsorption. We evaluated the importance of standardized food intake before and under the collection of feces. Material and Methods In a project, evaluating patients with suspected chronic pancreatitis (CP) and healthy volunteers (HC), stools were collected for 72 hours coupled to registration of nutritional intake over five consecutive days. Patient groups were created by a modified Layer score, which includes imaging findings, clinical parameters and pancreas function testing. Results We found 12 patients with CP, 11 patients without CP and 13 healthy individuals in our database. Median fecal fat in CP patients was 12 g/day, in non-CP patients 5 g/day and in healthy controls 5 g/day. Median fat absorption coefficient was 81% in those with chronic pancreatitis, 92% in those without CP and 92% in healthy controls. Corresponding median fat intake was 65 g/day, 68 g/day and 81 g/day in the respective groups. Spearman Rank Order Correlation between fecal fat (g/d) and fat absorption coefficient in all study subjects (n = 36) was good (-0.88 (p<0.001)). When we stratified groups according to fat intake, correlation between fecal fat and fat absorption was also good (-0.86 to -0.95). Conclusion In the diagnoses of fat malabsorption, calculating the ratio of fat absorption did not give additional information compared to fecal fat.