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Papers by Stephan Haas
![Research paper thumbnail of Corrigendum to “Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis” [Pancreatology 18(8) (2018) 847–854]](https://attachments.academia-assets.com/111456097/thumbnails/1.jpg)
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United European Gastroenterology Journal, 2020
BackgroundDiabetes mellitus is a common complication of chronic pancreatitis. It is traditionally... more BackgroundDiabetes 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.MethodsWe 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.ResultsThe 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 insufficien...
Pancreatology, 2019
Objective: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (C... more Objective: 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 etiological risk factors. Methods: This was a multicenter, cross-sectional study including 1509 patients with CP from the Scandinavian and Baltic countries. Patient and disease characteristics were compared for patients with calcifications (n=912) vs. without calcifications (n=597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications. Results: The mean age of patients was 53.9±14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different etiological risk factors (range: 2-69%). On multivariate analysis, alcoholic etiology (OR 1.76 [95% CI, 1.39-2.24]; p<0.001) and smoking (OR 1.77 [95% CI, 1.39-2.26], p<0.001) were positively associated with the presence of calcifications, while an autoimmune etiology 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 etiological 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.
Journal of Gastroenterology and Hepatology, 2019
and it is a condition of accessing publications that users recognise and abide by the legal requi... more and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.-Users may download and print one copy of any publication from the public portal for the purpose of private study or research.-You may not further distribute the material or use it for any profit-making activity or commercial gain-You may freely distribute the URL identifying the publication in the public portal-This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as
Journal of Clinical Medicine, 2019
Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with... more Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with a strong lymphocytic infiltration as the pathological hallmark and other organ involvement (OOI). IgG4-related kidney disease (IgG4-RKD) was first reported as an extrapancreatic manifestation of AIP in 2004. The aim of the present study was to determine the frequency and clinical impact of kidney lesions observed in patients with AIP type 1. Methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients with a histologically proven or highly probable diagnosis of AIP according to the International Consensus Diagnostic Criteria (ICDC) classification. Results: Seventy-one patients with AIP were evaluated. AIP type 1 was diagnosed in 62 (87%) patients. Kidney involvement was present in 17 (27.4%) patients with AIP type 1: 15 (88.2%) males and 2 (11.8%) females. Laboratory and/or imaging signs of kidney involvement were presented at the time of AIP...
American Journal of Gastroenterology, 2019
OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications a... more 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 commo...
Clinical and Translational Gastroenterology, 2018
Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies... more Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels. Methods: Multicentre cross-sectional study on CP patients diagnosed according to M-ANNHEIM criteria. Bone density was evaluated by dual-energy X-ray absorptiometry and pancreatic function by faecal elastase. Nutritional evaluation included vitamin D and vitamin K. Differences between patients with or without osteopathy were evaluated. The association between investigated variables and bone density were analysed with logistic regression analysis. Results: In total, 211 CP patients were enrolled at eight Centres (67% men; mean age 60). In total, 18% had advancedmarked CP, 56% suffered from pancreatic exocrine insufficiency and disease aetiology was alcoholic in 43%. Vitamin D and K were deficient in 56% and 32%, respectively. Osteopenia was diagnosed in 42% and osteoporosis in 22%. In the multivariate analysis, female sex (OR 2.78), age (OR 1.07 per year) and higher BMI (OR 0.84) were associated with the presence of osteoporosis. In male patients, the only factor associated with osteoporosis was vitamin K deficiency (OR 4.23). Conclusion: The present data confirm a high rate of osteopathy in CP patients and highlight the relevance of vitamin K deficiency as only factor associated with osteoporosis in male patients for the first time. Background Chronic pancreatitis (CP) is a fibro-inflammatory syndrome of the pancreas characterised by irreversible morphological changes that typically cause abdominal pain and can eventually result in permanent loss of the pancreatic function 1,2. The clinical presentation depends on disease stage, as in early phases episodes of abdominal pain are more frequent while, as the disease progresses, signs of pancreatic exocrine and endocrine insufficiency develop 1,3. Malnutrition due to exocrine pancreatic insufficiency, as well as alcohol abuse, chronic
Pancreatology, 2018
Background: In collaboration with United European Gastroenterology, the working group on 'Harmoni... more Background: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. Methods: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. Conclusions: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.
Nutrients, Jan 13, 2017
Morbid obesity is a lifelong disease, and all patients require complementary follow-up including ... more Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/o...
Molecular oncology, Oct 4, 2017
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantl... more Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into the TreatmentMAP software. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed, e.g. KRAS, TP53. Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all p...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Jan 18, 2017
We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pan... more We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospective...
United European gastroenterology journal, 2016
Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the... more Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the mucosa enabling en bloc removal of large lesions. The resulting larger mucosal defects have resulted in an increase in the occurrence of post-treatment strictures. Transplantation of autologous cell sheets, cultured from oral mucosa, has been shown to prevent post-ESD strictures. The aim of the study was to assess the efficacy and safety of cell sheet transplantation after oesophageal ESD in a Western patient population where reflux-associated pre-malignant and malignant conditions predominate. Patients with Barrett's oesophagus associated high-grade dysplasia or early adenocarcinoma where ESD entailed a resection >3 cm in length and ≥75% of the circumference were eligible for treatment under hospital exemption. Cell sheets were cultured from buccal mucosa according to Good Manufacturing Practice and were endoscopically applied to the post-ESD defect directly after resection. Pat...
United European gastroenterology journal, Mar 1, 2017
There have been substantial improvements in the management of chronic pancreatitis, leading to th... more There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and E...
Journal of the Pancreas, May 20, 2015
Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amon... more Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drugresistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro-and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down-and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomalprotein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover that these alterations are most likely a consequence of the multistep adaption towards gradual cytotoxic exposure culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options.
European journal of human genetics : EJHG, Aug 6, 2016
Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a fai... more Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls fr...
United European Gastroenterology Journal, 2015
BackgroundDiagnosis of pre‐malignant and malignant lesions in the bile duct and the pancreas is s... more BackgroundDiagnosis of pre‐malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC).AimsTo evaluate in a prospective cohort study the sensitivity and specificity of probe‐based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP).MethodsWe performed pCLE together with mother‐baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically‐resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year.ResultsWe were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagn...
Medical Radiology, 2010
... 174_2010_69, © Springer-Verlag Berlin Heidelberg 2011 A Cost Decision Analysis for Diagnosing... more ... 174_2010_69, © Springer-Verlag Berlin Heidelberg 2011 A Cost Decision Analysis for Diagnosing and Staging Stephan L. Haas, Konstantin von Heydwolff, and J.-Matthias Löhr SL Haas (*) Department of Medicine II, Gastroenterology ...
JOP : Journal of the pancreas, Jan 31, 2015
Due to maldigestion, pancreatic exocrine insufficiency (PEI) in chronic pancreatitis may lead to ... more Due to maldigestion, pancreatic exocrine insufficiency (PEI) in chronic pancreatitis may lead to deficiencies in fat-soluble vitamins, including vitamin D. This may, in turn, can cause disturbances in bone metabolism and reduce bone mineral density. To conduct a prospective study of maldigestion, bone metabolism, and bone mineral density in a group of patients with chronic pancreatitis. A total of 50 male patients with proven chronic pancreatitis (36/50 alcohol; 42/50 smokers) were studied. Pancreatic exocrine function was assessed using the fecal elastase-1 test. Blood and urine samples were analyzed for parameters related to pancreatitis, nutrition, endocrine status, and bone metabolism. Bone mineral density was measured with dual-energy X-ray absorption (DXA) and conventional vertebral X-rays. A standardized questionnaire for osteoporosis was given. Twenty-eight of the patients had PEI (fecal elastase-1 <200 µg/g), 25 had bone pain, and 21 had a history of bone fractures. Seru...
World journal of clinical cases, Jan 16, 2014
The case of a 32-year-old black woman of African descent who suffered from repeated episodes of a... more The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator (CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.
United European Gastroenterology Journal, 2020
BackgroundDiabetes mellitus is a common complication of chronic pancreatitis. It is traditionally... more BackgroundDiabetes 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.MethodsWe 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.ResultsThe 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 insufficien...
Pancreatology, 2019
Objective: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (C... more Objective: 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 etiological risk factors. Methods: This was a multicenter, cross-sectional study including 1509 patients with CP from the Scandinavian and Baltic countries. Patient and disease characteristics were compared for patients with calcifications (n=912) vs. without calcifications (n=597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications. Results: The mean age of patients was 53.9±14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different etiological risk factors (range: 2-69%). On multivariate analysis, alcoholic etiology (OR 1.76 [95% CI, 1.39-2.24]; p<0.001) and smoking (OR 1.77 [95% CI, 1.39-2.26], p<0.001) were positively associated with the presence of calcifications, while an autoimmune etiology 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 etiological 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.
Journal of Gastroenterology and Hepatology, 2019
and it is a condition of accessing publications that users recognise and abide by the legal requi... more and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.-Users may download and print one copy of any publication from the public portal for the purpose of private study or research.-You may not further distribute the material or use it for any profit-making activity or commercial gain-You may freely distribute the URL identifying the publication in the public portal-This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as
Journal of Clinical Medicine, 2019
Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with... more Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with a strong lymphocytic infiltration as the pathological hallmark and other organ involvement (OOI). IgG4-related kidney disease (IgG4-RKD) was first reported as an extrapancreatic manifestation of AIP in 2004. The aim of the present study was to determine the frequency and clinical impact of kidney lesions observed in patients with AIP type 1. Methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients with a histologically proven or highly probable diagnosis of AIP according to the International Consensus Diagnostic Criteria (ICDC) classification. Results: Seventy-one patients with AIP were evaluated. AIP type 1 was diagnosed in 62 (87%) patients. Kidney involvement was present in 17 (27.4%) patients with AIP type 1: 15 (88.2%) males and 2 (11.8%) females. Laboratory and/or imaging signs of kidney involvement were presented at the time of AIP...
American Journal of Gastroenterology, 2019
OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications a... more 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 commo...
Clinical and Translational Gastroenterology, 2018
Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies... more Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels. Methods: Multicentre cross-sectional study on CP patients diagnosed according to M-ANNHEIM criteria. Bone density was evaluated by dual-energy X-ray absorptiometry and pancreatic function by faecal elastase. Nutritional evaluation included vitamin D and vitamin K. Differences between patients with or without osteopathy were evaluated. The association between investigated variables and bone density were analysed with logistic regression analysis. Results: In total, 211 CP patients were enrolled at eight Centres (67% men; mean age 60). In total, 18% had advancedmarked CP, 56% suffered from pancreatic exocrine insufficiency and disease aetiology was alcoholic in 43%. Vitamin D and K were deficient in 56% and 32%, respectively. Osteopenia was diagnosed in 42% and osteoporosis in 22%. In the multivariate analysis, female sex (OR 2.78), age (OR 1.07 per year) and higher BMI (OR 0.84) were associated with the presence of osteoporosis. In male patients, the only factor associated with osteoporosis was vitamin K deficiency (OR 4.23). Conclusion: The present data confirm a high rate of osteopathy in CP patients and highlight the relevance of vitamin K deficiency as only factor associated with osteoporosis in male patients for the first time. Background Chronic pancreatitis (CP) is a fibro-inflammatory syndrome of the pancreas characterised by irreversible morphological changes that typically cause abdominal pain and can eventually result in permanent loss of the pancreatic function 1,2. The clinical presentation depends on disease stage, as in early phases episodes of abdominal pain are more frequent while, as the disease progresses, signs of pancreatic exocrine and endocrine insufficiency develop 1,3. Malnutrition due to exocrine pancreatic insufficiency, as well as alcohol abuse, chronic
Pancreatology, 2018
Background: In collaboration with United European Gastroenterology, the working group on 'Harmoni... more Background: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. Methods: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. Conclusions: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.
Nutrients, Jan 13, 2017
Morbid obesity is a lifelong disease, and all patients require complementary follow-up including ... more Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/o...
Molecular oncology, Oct 4, 2017
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantl... more Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into the TreatmentMAP software. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed, e.g. KRAS, TP53. Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all p...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Jan 18, 2017
We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pan... more We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospective...
United European gastroenterology journal, 2016
Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the... more Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the mucosa enabling en bloc removal of large lesions. The resulting larger mucosal defects have resulted in an increase in the occurrence of post-treatment strictures. Transplantation of autologous cell sheets, cultured from oral mucosa, has been shown to prevent post-ESD strictures. The aim of the study was to assess the efficacy and safety of cell sheet transplantation after oesophageal ESD in a Western patient population where reflux-associated pre-malignant and malignant conditions predominate. Patients with Barrett's oesophagus associated high-grade dysplasia or early adenocarcinoma where ESD entailed a resection >3 cm in length and ≥75% of the circumference were eligible for treatment under hospital exemption. Cell sheets were cultured from buccal mucosa according to Good Manufacturing Practice and were endoscopically applied to the post-ESD defect directly after resection. Pat...
United European gastroenterology journal, Mar 1, 2017
There have been substantial improvements in the management of chronic pancreatitis, leading to th... more There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and E...
Journal of the Pancreas, May 20, 2015
Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amon... more Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drugresistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro-and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down-and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomalprotein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover that these alterations are most likely a consequence of the multistep adaption towards gradual cytotoxic exposure culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options.
European journal of human genetics : EJHG, Aug 6, 2016
Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a fai... more Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls fr...
United European Gastroenterology Journal, 2015
BackgroundDiagnosis of pre‐malignant and malignant lesions in the bile duct and the pancreas is s... more BackgroundDiagnosis of pre‐malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC).AimsTo evaluate in a prospective cohort study the sensitivity and specificity of probe‐based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP).MethodsWe performed pCLE together with mother‐baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically‐resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year.ResultsWe were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagn...
Medical Radiology, 2010
... 174_2010_69, © Springer-Verlag Berlin Heidelberg 2011 A Cost Decision Analysis for Diagnosing... more ... 174_2010_69, © Springer-Verlag Berlin Heidelberg 2011 A Cost Decision Analysis for Diagnosing and Staging Stephan L. Haas, Konstantin von Heydwolff, and J.-Matthias Löhr SL Haas (*) Department of Medicine II, Gastroenterology ...
JOP : Journal of the pancreas, Jan 31, 2015
Due to maldigestion, pancreatic exocrine insufficiency (PEI) in chronic pancreatitis may lead to ... more Due to maldigestion, pancreatic exocrine insufficiency (PEI) in chronic pancreatitis may lead to deficiencies in fat-soluble vitamins, including vitamin D. This may, in turn, can cause disturbances in bone metabolism and reduce bone mineral density. To conduct a prospective study of maldigestion, bone metabolism, and bone mineral density in a group of patients with chronic pancreatitis. A total of 50 male patients with proven chronic pancreatitis (36/50 alcohol; 42/50 smokers) were studied. Pancreatic exocrine function was assessed using the fecal elastase-1 test. Blood and urine samples were analyzed for parameters related to pancreatitis, nutrition, endocrine status, and bone metabolism. Bone mineral density was measured with dual-energy X-ray absorption (DXA) and conventional vertebral X-rays. A standardized questionnaire for osteoporosis was given. Twenty-eight of the patients had PEI (fecal elastase-1 <200 µg/g), 25 had bone pain, and 21 had a history of bone fractures. Seru...
World journal of clinical cases, Jan 16, 2014
The case of a 32-year-old black woman of African descent who suffered from repeated episodes of a... more The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator (CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.