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103. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

Author

Goggins, Michael, Overbeek, Kasper Alexander, Brand, Randall, Syngal, Sapna, Del Chiaro, Marco, Bartsch, Detlef K, Bassi, Claudio, Carrato, Alfredo, Farrell, James, Fishman, Elliot K, Fockens, Paul, Gress, Thomas M, van Hooft, Jeanin E, Hruban, R H, Kastrinos, Fay, Klein, Allison, Lennon, Anne Marie, Lucas, Aimee, Park, Walter, Rustgi, Anil, Simeone, Diane, Stoffel, Elena, Vasen, Hans F A, Cahen, Djuna L, Canto, Marcia Irene, and Bruno, Marco

Abstract

Background and aimThe International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals).MethodsA modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed.ResultsConsensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATMmutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions.ConclusionsPancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

Published
2020
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104. P-LUM-06: Diagnostic accuracy of combined needle use of the new 20-gauge procore fine needle biopsy and the 25-gauge fine needle aspiration needle in solid gastrointestinal lesions

Author

van Riet, Priscilla, Arcidiacono, Paolo Giorgio, Petrone, Mariachiara, Dabizzi, Emanuele, Nguyen, Nam Quoc, Kitano, Masayuki, Chang, Kenneth, van der Merwe, Schalk, Bruno, Marco J., Cahen, Djuna L., Larghi, Alberto, Iglesias-Garcia, Julio, Giovannini, Marc, Santo, Erwin, Silva, Francisco Baldaque, Bucobo, Juan Carlos, Robert, Marie, Adeniran, Adebowale, Celli, Romulo, Aslanian, Harry, and Farrell, James

Subjects
Abstract
Abstract

Background and Objectives: Endoscopic ultrasound (EUS) fine needle biopsy (FNB) needles were designed to improve histologic yield, while maintaining the flexibility to permit ease of use. However, the diagnostic benefit of EUS-FNB needles as compared to the conventional fine needle aspiration (FNA) needles remains unclear. This study aimed to identify the diagnostic accuracy of combined needle use of a new 20-gauge ProCore FNB needle and a 25-gauge FNA needle. Methods: For this study, cases were selected in which both the 20-gauge ProCore FNB needle and the 25-gauge FNA needle were used during a single EUS procedure for sampling of a solid pancreatic mass, lymph node, or submucosal mass. Tissue acquisition was performed in the course of the ASPRO trial, a multicenter randomized study comparing the diagnostic value of 20-gauge ProCore FNB and 25-gauge FNA needles (ClinicalTrials.gov: NCT02167074). The protocol allowed additional sampling with the nonassigned needle, at the discretion of an endosonographer. Results: Of all 615 patients who were randomized for the ASPRO study, 74 were sampled with both needle types. In these combined needle cases, FNA was used first in 24 and ProCore FNB in 50 cases. Target lesions encompassed 39 solid pancreatic lesions, 18 submucosal masses, and 17 lymph nodes. Most pancreatic lesions were located in the head (25/39), lymph nodes were mainly located in the abdomen (15/18), and submucosal lesions were located in the stomach (8/20), esophagus (4/20), small intestines (3/20), and rectum (3/20). The main reason to use ProCore in addition to FNA was to collect more tissue for ancillary testing (79%). FNA was generally used in addition to ProCore to allow for on-site pathological assessment (76%). The regimen of FNA followed by ProCore resulted in 100% accuracy, while for ProCore followed by FNA, 88% was reached (P = 0.086). The type of target lesion, either pancreatic or nonpancreatic, did not affect the diagnostic accuracy of the two sampling regimens (odds ratio 1.2, 95% confidence interval 0.22–6.61, P = 0.834). Conclusion: FNA followed by ProCore FNB provides for a 100% diagnostic accuracy and tends to outperform ProCore FNB followed by FNA. Accuracy rates were independent of the type of target lesion.

Published
2017

105. The long-term impact of autoimmune pancreatitis on pancreatic function, quality of life, and life expectancy

Author

Buijs, Jorie, Cahen, Djuna L., Van Heerde, Marianne J., Rauws, Erik A., De Buy Wenniger, Lucas J Maillette, Hansen, Bettina E., Biermann, Katharina, Verheij, Joanne, Vleggaar, FP, Brink, Menno A., Beuers, Ulrich H W, Van Buuren, Henk R., Bruno, Marco J., Buijs, Jorie, Cahen, Djuna L., Van Heerde, Marianne J., Rauws, Erik A., De Buy Wenniger, Lucas J Maillette, Hansen, Bettina E., Biermann, Katharina, Verheij, Joanne, Vleggaar, FP, Brink, Menno A., Beuers, Ulrich H W, Van Buuren, Henk R., and Bruno, Marco J.

Published
2015

106. The long-term impact of autoimmune pancreatitis on pancreatic function, quality of life, and life expectancy

Author

MS MDL Oncologie, Infection & Immunity, Cancer, MS MDL 1, Buijs, Jorie, Cahen, Djuna L., Van Heerde, Marianne J., Rauws, Erik A., De Buy Wenniger, Lucas J Maillette, Hansen, Bettina E., Biermann, Katharina, Verheij, Joanne, Vleggaar, FP, Brink, Menno A., Beuers, Ulrich H W, Van Buuren, Henk R., Bruno, Marco J., MS MDL Oncologie, Infection & Immunity, Cancer, MS MDL 1, Buijs, Jorie, Cahen, Djuna L., Van Heerde, Marianne J., Rauws, Erik A., De Buy Wenniger, Lucas J Maillette, Hansen, Bettina E., Biermann, Katharina, Verheij, Joanne, Vleggaar, FP, Brink, Menno A., Beuers, Ulrich H W, Van Buuren, Henk R., and Bruno, Marco J.

Published
2015

107. The Long-Term Impact of Autoimmune Pancreatitis on Pancreatic Function, Quality of Life, and Life Expectancy

Author

Buijs, Jorie, primary, Cahen, Djuna L., additional, van Heerde, Marianne J., additional, Rauws, Erik A., additional, de Buy Wenniger, Lucas J. Maillette, additional, Hansen, Bettina E., additional, Biermann, Katharina, additional, Verheij, Joanne, additional, Vleggaar, Frank P., additional, Brink, Menno A., additional, Beuers, Ulrich H.W., additional, van Buuren, Henk R., additional, and Bruno, Marco J., additional

Published
2015
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113. Tu1484 Serum IgG4 in Acute, Chronic and Autoimmune Pancreatitis

Author

Buijs, Jorie, primary, Cahen, Djuna L., additional, Van Heerde, Marianne J., additional, Hollemans, Robbert A., additional, Hansen, Bettina E., additional, Besselink, Marc, additional, van Santvoort, Hjalmar C., additional, van Buuren, Henk R., additional, and Bruno, Marco J., additional

Published
2015
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114. Behandeling van chronische pancreatitis. Recente inzichten

Author

van der Gaag, Niels A., Boermeester, Marja A., Cahen, Djuna L., Busch, Olivier R. C., Rauws, Erik A. J., van Gulik, Thomas M., Bruno, Marco J., Gouma, Dirk J., Other departments, Amsterdam institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, Cancer Center Amsterdam, and Gastroenterology and Hepatology

Published
2009

115. Pancreatic Effects of Liraglutide or Sitagliptin in Overweight Patients With Type 2 Diabetes: A 12-Week Randomized, Placebo-Controlled Trial.

Author

Smits, Mark M., Tonneijck, Lennart, Muskiet, Marcel H. A., Kramer, Mark H. H., Pieters-van den Bos, Indra C., Vendrik, Karuna E. W., Hoekstra, Trynke, Bruno, Marco J., Diamant, Michaela, van Raalte, Daniël H., and Cahen, Djuna L.

Subjects
SITAGLIPTIN, METFORMIN, PHYSIOLOGICAL effects of hypoglycemic agents, TYPE 2 diabetes treatment, OVERWEIGHT persons, RANDOMIZED controlled trials, TYPE 2 diabetes complications, OBESITY complications, AMYLASES, BIOLOGICAL assay, COMPARATIVE studies, ENZYMES, HYPOGLYCEMIC agents, LIPASES, RESEARCH methodology, MEDICAL cooperation, TYPE 2 diabetes, PANCREAS, RESEARCH, STATISTICAL sampling, WHITE people, EVALUATION research, TREATMENT effectiveness, BLIND experiment
Abstract

Objective: To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology.Research Design and Methods: For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n = 19), sitagliptin 100 mg (n = 19), or matching placebos (n = 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI).Results: No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3 to 32.9; P = 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipase/amylase levels after 12 weeks. However, liraglutide increased lipase levels after 6 weeks (23.5 U/L [95% CI 2.1-44.8]; P = 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9]; P = 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2], P = 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9], P = 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm3 [95% CI -1.2 to 16.6]; P = 0.09). Treatment-induced volume expansion was associated with increased amylase levels.Conclusions: A 12-week treatment with liraglutide or sitagliptin only resulted in a brief and modest increase of plasma pancreatic enzyme concentrations in patients with type 2 diabetes. Apart from a minimal sitagliptin-induced increase in intraduodenal fluid secretion, pancreatic exocrine function was unaffected. The long-term clinical consequences of these discrete changes require further study. [ABSTRACT FROM AUTHOR]

Published
2017
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116. Tu1290 Long-Term Relapse Rates of Type 1 and 2 Autoimmune Pancreatitis

Author

Buijs, Jorie, primary, Cahen, Djuna L., additional, Van Heerde, Marianne J., additional, Rauws, Erik, additional, de Buy Wenniger, Lucas Maillette, additional, Hansen, Bettina E., additional, Biermann, Katharina, additional, Verheij, Joanne, additional, Vleggaar, Frank P., additional, Brink, Menno A., additional, Beuers, Ulrich, additional, van Buuren, Henk R., additional, and Bruno, Marco J., additional

Published
2014
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117. Tu1289 The Long-Term Impact of Autoimmune Pancreatitis: Treatment Outcome, Survival, Pancreatic Function, and Quality of Life

Author

Buijs, Jorie, primary, Cahen, Djuna L., additional, Van Heerde, Marianne J., additional, Rauws, Erik, additional, de Buy Wenniger, Lucas Maillette, additional, Hansen, Bettina E., additional, Biermann, Katharina, additional, Verheij, Joanne, additional, Vleggaar, Frank P., additional, Brink, Menno A., additional, Beuers, Ulrich, additional, van Buuren, Henk R., additional, and Bruno, Marco J., additional

Published
2014
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123. Endoscopic Versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis: Long-Term Outcome

Author

Cahen, Djuna L., primary, Gouma, Dirk J., additional, Laramee, Philippe, additional, Nio, Chung Y., additional, Rauws, Erik, additional, Boermeester, Marja A., additional, Busch, Olivier R., additional, Fockens, Paul, additional, Kuipers, Ernst J., additional, Pereira, Stephen P., additional, Wonderling, David, additional, Dijkgraaf, Marcel G., additional, and Bruno, Marco J., additional

Published
2011
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125. Evaluation of a Quality Assurance Program for Endoscopy Services in the Netherlands

Author

Sint Nicolaas, Jerome, primary, de Jonge, Vincent, additional, ter Borg, Frank, additional, Brouwer, Johannes T., additional, Cahen, Djuna L., additional, Kubben, Frank J., additional, Lesterhuis, Wilco, additional, Moolenaar, Willem, additional, Ouwendijk, Rob J., additional, Stolk, Mark, additional, Tang, Thjon J., additional, van Tilburg, Antonie J.P., additional, Valori, Roland M., additional, van Leerdam, Monique, additional, and Kuipers, Ernst J., additional

Published
2011
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126. Tu1446 Quality of Colonoscopy From a Patient's Perspective Using the Global Rating Scale

Author

Nicolaas, Jerome Sint, primary, De Jonge, Vincent, additional, Van Baalen, Onno, additional, Borg, Frank Ter, additional, Brouwer, Johannes T., additional, Cahen, Djuna L., additional, Colpaert, E.E., additional, Lesterhuis, Wilco, additional, Moolenaar, Willem, additional, Ouwendijk, Rob J., additional, Stolk, Mark, additional, Tang, Thjon J., additional, Van Tilburg, Antonie J.P., additional, Kuipers, Ernst J., additional, and Van Leerdam, Monique, additional

Published
2011
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127. Tu1474 Quality of Colonoscopy Reporting and Performance

Author

De Jonge, Vincent, primary, Nicolaas, Jerome Sint, additional, Van Baalen, Onno, additional, Borg, Frank Ter, additional, Brouwer, Johannes T., additional, Cahen, Djuna L., additional, Hadithi, Muhammed, additional, Lesterhuis, Wilco, additional, Moolenaar, Willem, additional, Ouwendijk, Rob J., additional, Stolk, Mark, additional, Tang, Thjon J., additional, Van Tilburg, Antonie J.P., additional, Kuipers, Ernst J., additional, and Van Leerdam, Monique, additional

Published
2011
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128. Mo1497 The First Prospective, Group Sequential Study Evaluating a New Type of Fully Covered Self Expandable Metal Stent for the Treatment of Benign Biliary Strictures

Author

Poley, Jan-Werner, primary, Metselaar, Herold J., additional, Van Buuren, Henk R., additional, Kazemier, Geert, additional, Van Eijck, Casper H., additional, Cahen, Djuna L., additional, Haringsma, Jelle, additional, Kuipers, Ernst J., additional, and Bruno, Marco J., additional

Published
2011
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129. Tu1496 The Occurrence of Adverse Events in a 30-Day Period After Colonoscopy

Author

De Jonge, Vincent, primary, Nicolaas, Jerome Sint, additional, Van Baalen, Onno, additional, Borg, Frank Ter, additional, Brouwer, Johannes T., additional, Cahen, Djuna L., additional, Ganesh, Sjam, additional, Lesterhuis, Wilco, additional, Moolenaar, Willem, additional, Ouwendijk, Rob J., additional, Stolk, Mark, additional, Tang, Thjon J., additional, Van Tilburg, Antonie J.P., additional, Kuipers, Ernst J., additional, and Van Leerdam, Monique, additional

Published
2011
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130. Mo1374 Differences in Adenoma Detection Rate Between Endoscopy Departments

Author

De Jonge, Vincent, primary, Sint Nicolaas, Jerome, additional, Van Baalen, Onno, additional, Ter Borg, Frank, additional, Brouwer, Johannes T., additional, Cahen, Djuna L., additional, Kubben, Frank J., additional, Lesterhuis, Wilco, additional, Moolenaar, Willem, additional, Ouwendijk, Rob J., additional, Stolk, Mark, additional, Tang, Thjon J., additional, Van Tilburg, Antonie J.P., additional, Van Leerdam, Monique, additional, and Kuipers, Ernst J., additional

Published
2011
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135. Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Author

Eshuis, Emma J, primary, Bemelman, Willem A, additional, van Bodegraven, Ad A, additional, Sprangers, Mirjam AG, additional, Bossuyt, Patrick MM, additional, de Wit, AW Marc van Milligen, additional, Crolla, Rogier MPH, additional, Cahen, Djuna L, additional, Oostenbrug, Liekele E, additional, Sosef, Meindert N, additional, Voorburg, Annet MCJ, additional, Davids, Paul HP, additional, van der Woude, C Janneke, additional, Lange, Johan, additional, Mallant, Rosalie C, additional, Boom, Maarten J, additional, Lieverse, Rob J, additional, van der Zaag, Edwin S, additional, Houben, Martin HMG, additional, Vecht, Juda, additional, Pierik, Robert EGJM, additional, van Ditzhuijsen, Theo JM, additional, Prins, Hubert A, additional, Marsman, Willem A, additional, Stockmann, Henricus B, additional, Brink, Menno A, additional, Consten, Esther CJ, additional, van der Werf, Sjoerd DJ, additional, Marinelli, Andreas WKS, additional, Jansen, Jeroen M, additional, Gerhards, Michael F, additional, Bolwerk, Clemens JM, additional, Stassen, Laurents PS, additional, Spanier, BW Marcel, additional, Bilgen, Ernst Jan Spillenaar, additional, van Berkel, Anne-Marie, additional, Cense, Huib A, additional, van Heukelem, Henk A, additional, van de Laar, Arnold, additional, Slot, Warner Bruins, additional, Eijsbouts, Quirijn A, additional, van Ooteghem, Nancy AM, additional, van Wagensveld, Bart, additional, van den Brande, Jan MH, additional, van Geloven, Anna AW, additional, Bruin, Karien F, additional, Maring, John K, additional, Oldenburg, Bas, additional, van Hillegersberg, Richard, additional, de Jong, Dirk J, additional, Bleichrodt, Robert, additional, van der Peet, Donald L, additional, Dekkers, Pascal EP, additional, Goei, T Hauwy, additional, and Stokkers, Pieter CF, additional

Published
2008
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136. Endoscopic Versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis: A Prospective Randomized Trial

Author

Cahen, Djuna L., primary, Gouma, Dirk J., additional, Nio, Yung, additional, Delhaye, Myriam, additional, Rauws, Erik A., additional, Boermeester, Marja A., additional, Busch, Olivier R., additional, Stoker, Jaap, additional, Laméris, Johan S., additional, Dijkgraaf, Marcel G., additional, Huibregtse, Kees, additional, Devière, Jacques, additional, and Bruno, Marco J., additional

Published
2005
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140. Surveillance for neoplasia in the pancreas

Author

Overbeek, Kasper A., Cahen, Djuna L., Canto, Marcia Irene, and Bruno, Marco J.

Abstract

Despite its low incidence in the general population, pancreatic cancer is one of the leading causes of cancer-related mortality. Survival greatly depends on operability, but most patients present with unresectable disease. Therefore, there is great interest in the early detection of pancreatic cancer and its precursor lesions by surveillance. Worldwide, several programs have been initiated for individuals at high risk for pancreatic cancer. Their first results suggest that surveillance in high-risk individuals is feasible, but their effectiveness in decreasing mortality remains to be proven. This review will discuss which individuals are eligible for surveillance, which lesions are aimed to be detected, and which surveillance modalities are being used in current clinical practice. Furthermore, it addresses the management of abnormalities found during surveillance and topics for future research.

Published
2016
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142. Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes.

Author

Smits, Mark M., Fluitman, Kristina S., Herrema, Hilde, Davids, Mark, Kramer, Mark H.H., Groen, Albert K., Belzer, Clara, de Vos, Willem M., Cahen, Djuna L., Nieuwdorp, Max, and van Raalte, Daniël H.

Subjects
GUT microbiome, TYPE 2 diabetes, ADULTS, SITAGLIPTIN, LIRAGLUTIDE
Abstract

Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D). A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA 1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma. Liraglutide decreased HbA 1c by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA 1c by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters. These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236). [ABSTRACT FROM AUTHOR]

Published
2021
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144. Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer.

Author

Levink, Iris J. M., Jansen, Maurice P. H. M., Azmani, Zakia, van IJcken, Wilfred, van Marion, Ronald, Peppelenbosch, Maikel P., Cahen, Djuna L., Fuhler, Gwenny M., and Bruno, Marco J.

Subjects
*PANCREATIC secretions, *PANCREATIC cancer, *SOMATIC mutation, *GENETIC variation, *CELL-free DNA
Abstract

Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m2 (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection n = 5, biopsy n = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, p < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 KRAS, 15 TP53, 2 SMAD4, 3 CDKN2A 1 CTNNB1, and 1 PIK3CA), 19 in PJ (3 KRAS, 15 TP53, and 1 SMAD4), and 8 in tissue (2 KRAS, 2 CDKN2A, and 4 TP53). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection. [ABSTRACT FROM AUTHOR]

Published
2023
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145. An 8q24 Gain in Pancreatic Juice Is a Candidate Biomarker for the Detection of Pancreatic Cancer.

Author

Levink, Iris J. M., Srebniak, Malgorzata I., De Valk, Walter G., van Veghel-Plandsoen, Monique M., Wagner, Anja, Cahen, Djuna L., Fuhler, Gwenny M., and Bruno, Marco J.

Subjects
*PANCREATIC secretions, *DYSPLASIA, *PANCREATIC cancer, *EARLY detection of cancer, *CELL-free DNA, *BIOMARKERS
Abstract

Secretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA) from PJ for PC detection. First, we confirmed the feasibility of shallow sequencing in PJ (n = 4), matched plasma (n = 3) and tissue samples (n = 4, microarray). Subsequently, shallow sequencing was performed on cfDNA from PJ of 26 cases (25 sporadic PC, 1 high-grade dysplasia) and 19 controls with a hereditary or familial increased risk of PC. 40 of the 45 PJ samples met the quality criteria for cfDNA analysis. Nine individuals had an 8q24 gain (oncogene MYC; 23%; eight cases (33%) and one control (6%), p = 0.04); six had both a 2q gain (STAT1) and 5p loss (CDH10; 15%; four cases (7%) and two controls (13%), p = 0.72). The presence of an 8q24 gain differentiated the cases and controls, with a sensitivity of 33% (95% CI 16–55%) and specificity of 94% (95% CI 70–100%). The presence of either an 8q24 or 2q gain with a 5p loss was related to a sensitivity of 50% (95% CI 29–71%) and specificity of 81% (95% CI 54–96%). Shallow sequencing of PJ is feasible. The presence of an 8q24 gain in PJ shows promise as a biomarker for the detection of PC. Further research is required with a larger sample size and consecutively collected samples in high-risk individuals prior to implementation in a surveillance cohort. [ABSTRACT FROM AUTHOR]

Published
2023
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146. THU-120-YI The impact of ursodeoxycholic acid on biochemistry of patients with primary biliary cholangitis in a nationwide cohort.

Author

Werner, Ellen, van Hooff, Maria C., van der Maas, Gerjan J., de Veer, Rozanne C., Beuers, Ulrich, Drenth, Joost P.H., Cuperus, Frans J.C., van Hoek, Bart, Veldt, Bart J., Klemt-Kropp, Michael, van Meer, Suzanne, Verdonk, Robert C., Flink, Hajo J., Vrolijk, Jan Maarten, Gevers, Tom J.G., Ponsioen, Cyriel Y., de Kort, Sander, van Putten, Paul G., Cahen, Djuna L., and van der Waaij, Lauren A.

Published
2024
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148. Pancreatic cancer surveillance: Risk stratification of individuals with a germline CDKN2A pathogenic variant.

Author

Klatte DCF, Meziani J, Cahen DL, van Diepen M, Bruno MJ, and van Leerdam ME

Subjects
Humans, Male, Risk Assessment methods, Female, Middle Aged, Risk Factors, Aged, Netherlands epidemiology, Adult, Smoking adverse effects, Smoking epidemiology, Early Detection of Cancer methods, Pancreatic Neoplasms genetics, Pancreatic Neoplasms epidemiology, Germ-Line Mutation, Cyclin-Dependent Kinase Inhibitor p16 genetics, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal epidemiology, Genetic Predisposition to Disease
Abstract

Background: Individuals carrying a germline CDKN2A pathogenic variant (PV) are at a high risk of developing pancreatic ductal adenocarcinoma. Risk stratification could allow tailored surveillance., Objective: To develop a Fine-Gray prediction model for the risk of PDAC in carriers of a CDKN2A PV., Methods: Data from two large Dutch pancreatic cancer surveillance programs were used. A limited set of predictor variables were selected bsased on previous literature and the clinical expertise of the study group., Results: A total of 506 CDKN2A PV carriers were included, among whom we showed a substantial lifetime risk of PDAC (23%). The model identifies having a first-degree relative with PDAC (B = 0.7256) and a history of smoking (B = 0.4776) as significant risk factors. However, the model shows limited discrimination (c-statistic 0.64) and calibration., Conclusion: Our study highlights the high lifetime risk of PDAC in carriers of a CDKN2A PV. While identifying significant risk factors such as family history of PDAC and smoking, our prediction model shows limited precision, highlighting the need for additional factors such as biomarkers to improve its clinical utility for tailored surveillance of high-risk individuals., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Published
2024
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149. Assessment of Glucose and HbA1c Monitoring in a Pancreatic Cancer Surveillance Program for High-Risk Individuals.

Author

Meziani J, de Jong JGY, Fuhler GM, Koopmann BDM, Levink IJM, Fockens P, Vleggaar FP, Bruno MJ, and Cahen DL

Subjects
Humans, Middle Aged, Male, Female, Aged, Adult, Diabetes Mellitus blood, Diabetes Mellitus diagnosis, Diabetes Mellitus epidemiology, Risk Factors, Magnetic Resonance Imaging, Endosonography, Follow-Up Studies, Glycated Hemoglobin analysis, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms blood, Pancreatic Neoplasms epidemiology, Blood Glucose analysis, Carcinoma, Pancreatic Ductal blood, Carcinoma, Pancreatic Ductal diagnosis, Early Detection of Cancer methods
Abstract

Introduction: Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance., Methods: Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates., Results: Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development., Discussion: In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Published
2024
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