Publications by authors named "Djuna L Cahen"

47 Publications

Long-term yield of pancreatic cancer surveillance in high-risk individuals.

Gut 2021 Apr 5. Epub 2021 Apr 5.

Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Objective: We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.

Design: From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.

Results: 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1-32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).

Conclusion: The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
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http://dx.doi.org/10.1136/gutjnl-2020-323611DOI Listing
April 2021

Identifying key factors for the effectiveness of pancreatic cancer screening: A model-based analysis.

Int J Cancer 2021 Feb 28. Epub 2021 Feb 28.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for "Progressive-only" vs -41% for "Indolent Included"). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.
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http://dx.doi.org/10.1002/ijc.33540DOI Listing
February 2021

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

Diabetes Metab 2021 Jan 8;47(5):101223. Epub 2021 Jan 8.

Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Location VUmc, Amsterdam, The Netherlands.

Aim: 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).

Methods: A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m, HbA 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.

Results: Liraglutide decreased HbA 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 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.

Conclusion: 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).
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http://dx.doi.org/10.1016/j.diabet.2021.101223DOI Listing
January 2021

Optimization of Pancreatic Juice Collection: A First Step Toward Biomarker Discovery and Early Detection of Pancreatic Cancer.

Am J Gastroenterol 2020 12;115(12):2103-2108

Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Introduction: Imaging-based surveillance programs fail to detect pancreatic ductal adenocarcinoma at a curable stage, creating an urgent need for diagnostic biomarkers.

Methods: Secretin-stimulated pancreatic juice (PJ) was collected from the duodenal lumen during endoscopic ultrasound. The yield of biomarkers and organoids was compared for 2 collection techniques (endoscope suction channel vs catheter-based) and 3 periods (0-4 vs 4-8 vs 8-15 minutes).

Results: Collection through the endoscope suction channel was superior to collection with a catheter. Collection beyond 8 minutes reduced biomarker yield. PJ-derived organoid culture was feasible.

Discussion: The optimal protocol for secretin-stimulated PJ collection is through the endoscope suction channel for 8 minutes allowing biomarker detection and organoid culture.
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http://dx.doi.org/10.14309/ajg.0000000000000939DOI Listing
December 2020

Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

Diagn Cytopathol 2021 Feb 24;49(2):295-302. Epub 2020 Oct 24.

Department of Pathology, Erasmus MC University Medical Center Rotterdam, the Netherlands and Institute for Pathology, Dueren, Germany.

Background: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff.

Methods: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions.

Results: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10).

Conclusion: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.
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http://dx.doi.org/10.1002/dc.24645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820998PMC
February 2021

Comparison of fine-needle aspiration and fine-needle biopsy devices for endoscopic ultrasound-guided sampling of solid lesions: a systemic review and meta-analysis.

Endoscopy 2021 Apr 24;53(4):411-423. Epub 2020 Jun 24.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background:  Endoscopic ultrasound (EUS)-guided tissue acquisition is extensively used, but the optimal sampling device is still a matter of debate. We performed meta-analyses on studies comparing fine-needle aspiration (FNA) with fine-needle biopsy (FNB) needles, and studies comparing different FNB needles.

Methods:  Online databases were searched for randomized controlled trials (RCTs) of at least 50 cases with a suspected solid pancreatic or nonpancreatic lesion that compared FNA with FNB needles. Outcome measures included diagnostic accuracy, adequacy, number of passes, presence of tissue cores, and adverse events. We also performed meta-regression analysis on the effect of FNB design on diagnostic accuracy. Quality was assessed using the QUADAS-2 tool.

Results:  18 RCTs comparing FNA with FNB needles were included. FNB provided a higher pooled diagnostic accuracy (87 % vs. 80 %;  = 0.02) and tissue core rate (80 % vs. 62 %;  = 0.002), and allowed diagnosis with fewer passes ( = 0.03), in both pancreatic and nonpancreatic lesions. A total of 93 studies were included comparing different FNB devices. Pooled diagnostic accuracy was higher for forward-facing bevel needles than for the reverse bevel needle. In this analysis, study quality was low and heterogeneity was high (  = 80 %).

Conclusion:  FNB outperformed FNA when sampling pancreatic and nonpancreatic lesions. Forward-facing bevel FNB needles seemed to outperform the reverse bevel FNB needle, but the low quality of evidence prevents us from making strong recommendations on the optimal FNB design.
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http://dx.doi.org/10.1055/a-1206-5552DOI Listing
April 2021

Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic variants.

J Med Genet 2021 Apr 1;58(4):264-269. Epub 2020 Jun 1.

Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

Background: Pathogenic variants in the gene are generally associated with the development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist and the extent of PDAC risk is not well established for many variants.

Methods: Using the Dutch national familial melanoma database, we identified all families with a pathogenic variant and investigated the occurrence of PDAC within these families. We also estimated the standardised incidence ratio and lifetime PDAC risk for carriers of a highly prevalent variant in these families.

Results: We identified 172 families in which 649 individuals carried 15 different pathogenic variants. The most prevalent variant was the founder mutation c.225_243del (p16-, 484 proven carriers). Second most prevalent was c.67G>C (55 proven carriers). PDAC developed in 95 of 163 families (58%, including 373 of 629 proven carriers) harbouring a variant with an effect on the p16INK4a protein, whereas PDAC did not occur in the 9 families (20 proven carriers) with a variant affecting only p14ARF. In the c.67G>C families, PDAC occurred in 12 of the 251 (5%) persons at risk. The standardised incidence ratio was 19.1 (95% CI 8.3 to 33.6) and the cumulative PDAC incidence at age 75 years (lifetime risk) was 19% (95% CI 7.5% to 30.1%).

Conclusions: Our results support the notion that pathogenic variants affecting the p16INK4a protein, including c.67G>C, are associated with increased PDAC risk and carriers of such variants should be offered pancreatic cancer surveillance. There is no clinical evidence that impairment of only the p14ARF protein leads to an increased PDAC risk.
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http://dx.doi.org/10.1136/jmedgenet-2019-106562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005797PMC
April 2021

Fully covered self-expandable metal stents for benign biliary strictures: an effective alternative.

Authors:
Djuna L Cahen

Endoscopy 2020 05 22;52(5):334-335. Epub 2020 Apr 22.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1055/a-1137-4541DOI Listing
May 2020

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance.

Fam Cancer 2020 07;19(3):247-258

Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaffected by the intensified surveillance period. Of the 10 operated patients, 1 (10%) developed diabetes and 7 (70%) pancreatic exocrine insufficiency. The interviews yielded median quality-of-life scores comparable to the general population. Also, after surgery, patients' attitudes towards surveillance were unchanged (5/10, 50%) or became more positive (4/10, 40%). Although patients were aware of the (sometimes benign) pathological outcome, when asked if surgery had been justified, only 20% (2/10) disagreed, and all would again have chosen to undergo surgery. In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substantial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance.
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http://dx.doi.org/10.1007/s10689-020-00171-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242488PMC
July 2020

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Endosc Int Open 2020 Feb 22;8(2):E155-E162. Epub 2020 Jan 22.

Department of Pathology, Erasmus MC University Medical Center Rotterdam, the Netherlands.

 The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71),  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42),  = 0.56) or Cell block (62 % (39/63),  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42),  = 0.02) or Cell block samples (40 % (25/63),  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70,  = 0.98), but lower for ThinPrep (ĸ = 0.26,  = 0.01) than smears. After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.
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http://dx.doi.org/10.1055/a-1038-4103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976322PMC
February 2020

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

Gut 2020 01 31;69(1):7-17. Epub 2019 Oct 31.

Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background And Aim: The 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).

Methods: A 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.

Results: Consensus 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 mutation 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.

Conclusions: Pancreatic 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.
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http://dx.doi.org/10.1136/gutjnl-2019-319352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295005PMC
January 2020

Pancreatic cyst surveillance imposes low psychological burden.

Pancreatology 2019 Dec 5;19(8):1061-1066. Epub 2019 Sep 5.

Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background/objectives: For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective.

Methods: The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance.

Results: 109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, P = 0.035), postponing plans (32% vs 13%, P = 0.031), and finding the follow-up burdensome (33% vs 13%, P = 0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)).

Conclusion: The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.
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http://dx.doi.org/10.1016/j.pan.2019.08.011DOI Listing
December 2019

Editorial: when, who and how-the ever-evolving management of pancreatic cystic lesions. Authors' reply.

Aliment Pharmacol Ther 2019 10;50(7):829-830

Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1111/apt.15492DOI Listing
October 2019

Development of a stratification tool to identify pancreatic intraductal papillary mucinous neoplasms at lowest risk of progression.

Aliment Pharmacol Ther 2019 10 19;50(7):789-799. Epub 2019 Aug 19.

Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Because most pancreatic intraductal papillary mucinous neoplasms (IPMNs) will never become malignant, currently advocated long-term surveillance is low-yield for most individuals.

Aim: To develop a score chart identifying IPMNs at lowest risk of developing worrisome features or high-risk stigmata.

Methods: We combined prospectively maintained pancreatic cyst surveillance databases of three academic institutions. Patients were included if they had a presumed side-branch IPMN, without worrisome features or high-risk stigmata at baseline (as defined by the 2012 international Fukuoka guidelines), and were followed ≥ 12 months. The endpoint was development of one or more worrisome features or high-risk stigmata during follow-up. We created a multivariable prediction model using Cox-proportional logistic regression analysis and performed an internal-external validation.

Results: 875 patients were included. After a mean follow-up of 50 months (range 12-157), 116 (13%) patients developed worrisome features or high-risk stigmata. The final model included cyst size (HR 1.12, 95% CI 1.09-1.15), cyst multifocality (HR 1.49, 95% CI 1.01-2.18), ever having smoked (HR 1.40, 95% CI 0.95-2.04), history of acute pancreatitis (HR 2.07, 95% CI 1.21-3.55), and history of extrapancreatic malignancy (HR 1.34, 95% CI 0.91-1.97). After validation, the model had good discriminative ability (C-statistic 0.72 in the Mayo cohort, 0.71 in the Columbia cohort, 0.64 in the Erasmus cohort).

Conclusion: In presumed side branch IPMNs without worrisome features or high-risk stigmata at baseline, the Dutch-American Risk stratification Tool (DART-1) successfully identifies pancreatic lesions at low risk of developing worrisome features or high-risk stigmata.
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http://dx.doi.org/10.1111/apt.15440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772152PMC
October 2019

Combined versus single use 20 G fine-needle biopsy and 25 G fine-needle aspiration for endoscopic ultrasound-guided tissue sampling of solid gastrointestinal lesions.

Endoscopy 2020 01 22;52(1):37-44. Epub 2019 Jul 22.

Department of Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, United States.

Background: Instead of choosing one endoscopic ultrasound (EUS) needle over the other, some advocate the use of fine-needle aspiration (FNA) and fine-needle biopsy (FNB) consecutively. We explored the yield of combined use of 20 G FNB and 25 G FNA needles in patients with a suspicious solid gastrointestinal lesion.

Methods: Patients from the ASPRO study who were sampled with both needles during the same procedure were included. The incremental yield of dual sampling compared with the yield of single needle use on the diagnostic accuracy for malignancy was assessed for both dual sampling approaches - FNA followed by FNB, and vice versa.

Results: 73 patients were included. There were 39 (53 %) pancreatic lesions, 18 (25 %) submucosal masses, and 16 (22 %) lymph nodes. FNA was used first in 24 patients (33 %) and FNB was used first in 49 (67 %). Generally, FNB was performed after FNA to collect tissue for ancillary testing (75 %), whereas FNA was used after FNB to allow for on-site pathological assessment (76 %). Diagnostic accuracy for malignancy of single needle use increased from 78 % to 92 % with dual sampling ( = 0.002). FNA followed by FNB improved the diagnostic accuracy for malignancy ( = 0.03), whereas FNB followed by FNA did not ( = 0.13).

Conclusion: Dual sampling only improved diagnostic accuracy when 25 G FNA was followed by 20 G FNB and not vice versa. As the diagnostic benefit of the 20 G FNB over the 25 G FNA needle has recently been proven, sampling with the FNB needle seems a logical first choice.
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http://dx.doi.org/10.1055/a-0966-8755DOI Listing
January 2020

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

Dig Endosc 2019 Nov 10;31(6):690-697. Epub 2019 Jul 10.

Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Aim: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists.

Methods: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens.

Results: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432).

Conclusion: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers.
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http://dx.doi.org/10.1111/den.13424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900144PMC
November 2019

A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device.

Gastrointest Endosc 2019 02 24;89(2):329-339. Epub 2018 Oct 24.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Background And Aims: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle.

Methods: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders.

Results: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836).

Conclusion: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).
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http://dx.doi.org/10.1016/j.gie.2018.10.026DOI Listing
February 2019

Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer.

Endosc Int Open 2018 May 18;6(5):E541-E548. Epub 2018 Apr 18.

Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Study Aims : During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.

Patients And Methods : Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.

Results : A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86 % (2012) and 81 % (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83 %. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β = - 1.6,  = 0.005).

Conclusions : This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.
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http://dx.doi.org/10.1055/a-0574-2396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909773PMC
May 2018

Predictors of Progression Among Low-Risk Intraductal Papillary Mucinous Neoplasms in a Multicenter Surveillance Cohort.

Pancreas 2018 Apr;47(4):471-476

Objectives: Our aim was to identify baseline characteristics associated with disease progression and malignant transformation in low-risk suspected intraductal papillary mucinous neoplasms (IPMNs).

Methods: This is a retrospective cohort study of prospectively maintained databases of pancreatic cysts at 3 international, academic institutions. Five hundred fifty-nine adult patients with clinically suspected asymptomatic IPMN evaluated by radiologic studies or endoscopic ultrasound between 2003 and 2013 without worrisome features and under surveillance for 12 months or longer were included. We evaluated the relationship of baseline demographics and cyst features to disease progression (size increase, development of worrisome features, or high-grade dysplasia/cancer).

Results: After a median of 44 months follow-up, 269 (48%) patients experienced cyst size increase, 68 (12%) developed worrisome features, and 11 (2%) developed high-grade dysplasia/cancer. In multivariable Cox-regression analysis, no baseline characteristics were associated with size increase. An initial cyst size of 2 cm or greater, multifocality, history of prostate cancer, and smoking were the strongest predictors of development of new worrisome features. Univariable analysis found male sex, diabetes, and recent weight loss associated with development of high-grade dysplasia/cancer.

Conclusions: Our study demonstrates that low-risk suspected IPMNs carry a small but clinically relevant risk of disease progression and provides data on baseline characteristics that may help in risk stratification.
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http://dx.doi.org/10.1097/MPA.0000000000001027DOI Listing
April 2018

Pancreatic Steatosis Is Not Associated With Exocrine Pancreatic Function in Overweight Type 2 Diabetes Patients.

Pancreas 2017 10;46(9):e75-e76

Diabetes Center, Department of Internal Medicine VU University Medical Center Amsterdam, The Netherlands Department of Physics and Medical Technology VU University Medical Center Amsterdam, The Netherlands Department of Radiology and Nuclear Medicine VU University Medical Center Amsterdam, The Netherlands Diabetes Center, Department of Internal Medicine VU University Medical Center Amsterdam, The Netherlands Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam, The Netherlands Diabetes Center, Department of Internal Medicine VU University Medical Center Amsterdam, The Netherlands.

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http://dx.doi.org/10.1097/MPA.0000000000000893DOI Listing
October 2017

A biodegradable non-covered self-expandable stent to treat pancreatic duct strictures in chronic pancreatitis: a proof of principle.

Gastrointest Endosc 2018 02 24;87(2):486-491. Epub 2017 Aug 24.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background And Aims: In chronic pancreatitis (CP), fibrotic pancreatic duct (PD) strictures pose a therapeutic challenge, because endoscopic dilatation requires multiple procedures with suboptimal results. Biodegradable self-expandable stents (BD-SESs) may serve as an alternative in this setting.

Methods: Patients with CP were eligible for this proof-of-principle study if at least 6 months of endoscopic dilatation with plastic stents had failed to resolve their PD stricture. The non-covered BD-SESs were expected to degrade within 3 to 6 months. Patients were followed at 3-monthly intervals for 1 year. Placement success and safety were the primary outcome parameters. Stricture resolution was assessed by ERCP after 6 months.

Results: BD-SESs were successfully placed in all 19 patients without adverse events. In 2 cases, stent occlusion with sludge and stones was treated by a balloon swipe. One stent disintegrated during this procedure, after which placement of the plastic stent was resumed. A hyperplastic response was observed in 2 patients but did not result in functional obstruction. Stricture resolution was accomplished in 11 patients (technical success rate 58%). Six patients required further treatment of their PD stricture, 4 endoscopically and 2 surgically. Three additional patients underwent surgery for other reasons: 2 Whipple procedures for CP-related adverse events and one tail resection for an intraductal papillary mucinous neoplasm. The remaining 10 patients did not require further PD drainage (clinical success rate 52%).

Conclusions: These preliminary results show that BD-SESs are safe to use and able to resolve fibrotic PD strictures in CP. These encouraging outcomes warrant further testing.
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http://dx.doi.org/10.1016/j.gie.2017.08.018DOI Listing
February 2018

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

Diabetes Care 2017 Mar 20;40(3):301-308. Epub 2016 Dec 20.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

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 ( = 19), sitagliptin 100 mg ( = 19), or matching placebos ( = 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; = 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]; = 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9]; = 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2], = 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9], = 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm [95% CI -1.2 to 16.6]; 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.
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http://dx.doi.org/10.2337/dc16-0836DOI Listing
March 2017

Surveillance for neoplasia in the pancreas.

Best Pract Res Clin Gastroenterol 2016 Dec 5;30(6):971-986. Epub 2016 Nov 5.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bpg.2016.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552042PMC
December 2016

Testing for Anti-PBP Antibody Is Not Useful in Diagnosing Autoimmune Pancreatitis.

Am J Gastroenterol 2016 11 21;111(11):1650-1654. Epub 2016 Jun 21.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Objectives: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, clinically mimicking pancreatic cancer. In 2009, a serological diagnostic test detecting antibodies against plasminogen-binding protein (PBP) of Helicobacter pylori was reported with outstanding test performances (NEJM 361:135). We aimed to validate these findings.

Methods: Between March 2007 and May 2011, sera were collected from consecutive patients presenting with type 1 AIP, pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), primary sclerosing cholangitis (PSC), and healthy controls (HC) with or without antibodies against H. pylori. Serum antibody binding to synthetic PBP peptide was quantified by enzyme-linked immunosorbent assay (ELISA), using standard curves of custom-made PBP rabbit polyclonal antibodies. A synthetic Flag peptide (DYKDDDK), to which no antibodies are found in human serum, was included as negative control.

Results: High sensitivity of PBP peptide recognition was demonstrated by selective binding of PBP peptide over Flag peptide by PBP-immunized rabbit serum. Competition assays with PBP peptide validated the selectivity for antibodies recognizing this antigen. A total of 114 patients were subsequently tested: 34 AIP, 29 PDAC, 17 CP, 16 PSC, and 18 HCs (9 positive and 9 negative for H. pylori). No significant differences in detection of antibodies against the PBP peptide were found between different the patient groups and healthy controls.

Conclusions: Using a sensitive and selective ELISA-based assay, we did not find increased serum antibodies against PBP peptide in AIP patients. PBP serum antibodies are therefore not a useful diagnostic tool to diagnose AIP.
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http://dx.doi.org/10.1038/ajg.2016.241DOI Listing
November 2016

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial.

Diabetologia 2016 12 15;59(12):2588-2593. Epub 2016 Sep 15.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Aims/hypothesis: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes.

Methods: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg (n = 17), sitagliptin 100 mg (n = 18) or matching placebos (n = 17) by computer generated numbers. Both participants and researchers were blinded to group assignment. Hepatic fat content was measured using proton magnetic resonance spectroscopy (H-MRS). Hepatic fibrosis was estimated using three validated formulae.

Results: One patient dropped out in the sitagliptin group owing to dizziness, but no serious adverse events occurred. At week 12, no between-group differences in hepatic steatosis were found. Liraglutide reduced steatosis by 10% (20.9 ± 3.4% to 18.8 ± 3.3%), sitagliptin reduced steatosis by 12.1% (23.9 ± 3.0% to 21.0 ± 2.7%) and placebo lessened it by 9.5% (18.7 ± 2.7% to 16.9 ± 2.7%). Neither drug affected hepatic fibrosis scores compared with placebo.

Conclusions/interpretation: Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes.

Trial Registration: ClinicalTrials.gov NCT01744236 FUNDING : Funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 - the SAFEGUARD project.
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http://dx.doi.org/10.1007/s00125-016-4100-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518065PMC
December 2016

Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients.

Diabetes Obes Metab 2016 12 30;18(12):1217-1225. Epub 2016 Aug 30.

Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands.

Aims: Treatment with glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors might increase gallstone formation; however, the mechanisms involved are unknown. We aimed to assess the effects of these drugs on gallbladder volume and bile acid profile.

Materials And Methods: A total of 57 type 2 diabetes patients (mean ± SD age, 62.8 ± 6.9 years; BMI, 31.8 ± 4.1 kg/m ; HbA1c, 7.3% ± 0.6%), treated with metformin and/or sulfonylureas, were included in this 12-week randomized, placebo-controlled, double-blind, single-centre trial between July 2013 and August 2015 at the VU University Medical Center, the Netherlands. Patients received the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebo for 12 weeks. Gallbladder fasting volume and ejection fraction were measured using ultrasonography after a high-fat meal. Serum bile acids were measured in the fasting and postprandial state and in faecal samples. The trial was registered at ClinicalTrials.gov (NCT01744236).

Results: Neither liraglutide nor sitagliptin had an effect on gallbladder fasting volume and ejection fraction (p > .05). Liraglutide increased serum levels of deoxycholic acid in the fasting state [0.20 µmol/L (95% CI 0.027-0.376), p = 0.024] and postprandial state [AUC 40.71 (13.22-68.21), p = 0.005] and in faeces [ratio 1.5 (1.03-2.19); p = 0.035]. Sitagliptin had no effect on serum bile acids, but increased faecal levels of chenodeoxycholic acid [ratio 3.42 (1.33-8.79), p = 0.012], cholic acid [ratio 3.32 (1.26-8.87), p = 0.017] and ursodeoxycholic acid [ratio 3.81 (1.44-10.14), p = 0.008].

Conclusions: Neither liraglutide nor sitagliptin has an effect on gallbladder volume. Observed changes in bile acids with liraglutide suggest alterations in the intestinal microbiome, while sitagliptin appears to increase hepatic bile acid production.
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http://dx.doi.org/10.1111/dom.12748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129471PMC
December 2016

Mapping international practice patterns in EUS-guided tissue sampling: outcome of a global survey.

Endosc Int Open 2016 Mar;4(3):E360-70

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Study Aims: Although Endoscopic Ultrasound (EUS)-guided tissue sampling is widely used, the optimal sampling strategy remains subject of debate. We evaluated practice patterns within the international endosonographic community.

Patients And Methods: An online questionnaire was sent to 400 endosonographers from the United States, Europe, and Asia.

Results: A total of 186 (47 %) endosonographers participated: United States 54 (29 %), Europe 85 (46 %), and Asia 47 (25 %). European (75 %) and Asian (84 %) respondents routinely check coagulation status, whereas US respondents only check on indication (64 %, P = 0.007). While propofol sedation is standard in the United States (83 %), conscious sedation is still widely used in Europe (52 %) and Asia (84 %, P < 0.001). Overall, the 22-gauge needle is most commonly used (52 %). For fine-needle aspiration (FNA) of solid pancreatic lesions, 22-gauge (45 %) and 25-gauge (49 %) needles are used equally. For fine-needle biopsy (FNB) of solid masses, the 25-gauge device is less favored than the 22-gauge FNA device (49 % versus 21 %). The 19-gauge needle is generally used for FNB of submucosal masses (62 %). Rapid on-site pathological evaluation (ROSE) is utilized more often by US (98 %) than by European and Asian respondents (51 %, P < 0.001). Cytolyt (52 %), formalin (15 %) and alcohol (15 %) are used for FNA specimen preservation in the United States and Europe, while saline (27 %) and alcohol (38 %) are widely used in Asia (P < 0.001).

Conclusions: EUS-guided tissue sampling practices vary substantially within the international endosonographic community and differ considerably from recommendations expressed in guidelines. Because the clinical relevance of these variations is largely unknown, the outcome of this survey suggests a need for further studies.
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http://dx.doi.org/10.1055/s-0042-101023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873668PMC
March 2016

Follow-up of asymptomatic pancreatic cysts in clinical practice: A vignette questionnaire.

Pancreatology 2016 May-Jun;16(3):416-22. Epub 2016 Feb 23.

Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.

Background/objectives: In absence of evidence-based guidelines of pancreatic cystic neoplasms (PCN), the management might vary among physicians. The aim of this survey was to assess the attitude of Dutch gastroenterologists (GE) towards the management of asymptomatic PCNs.

Methods: An anonymous online questionnaire was distributed to all practicing GE (n = 381) in The Netherlands, in which four vignette patients with PCN were presented.

Results: In total 45% of GE responded. Most respondents would perform surveillance for a 10 mm PCN (78%) mainly with an interval of one year (57%). A shorter interval of three (26%) or six (57%) months was chosen for a 25 mm BD-IPMN. Ultrasound was recommended for surveillance by 19% for a 10 mm cyst. GE with EUS experience were more likely to apply EUS for surveillance of 10 mm cyst than those without (56% vs 28%; p < 0.001). The presence of a branch-duct intraductal mucinous neoplasm (BD-IPMN) with a mural nodule, dilated pancreatic duct (8 mm) or increased serum CA 19.9 (300 U/ml) were considered an indication for resection by respectively 88%, 68% and 51% of respondents.

Conclusion: Dutch GE demonstrate substantial variability in the management of asymptomatic PCNs. A significant proportion of general GE still use ultrasound for surveillance of small PCNs, while GE with EUS experience were more likely to perform EUS. The presence of risk factors for malignant degeneration of IPMN were not recognized by a substantial proportion of GE. Data on the natural history of PCNs is required to provide input for evidence-based guidelines, which should lead to a more uniform approach.
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http://dx.doi.org/10.1016/j.pan.2016.02.007DOI Listing
March 2017

GLP-1 based therapies: clinical implications for gastroenterologists.

Gut 2016 Apr 19;65(4):702-11. Epub 2016 Jan 19.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.

The gut-derived incretin hormone, glucagon-like peptide 1 (GLP-1) lowers postprandial blood glucose levels by stimulating insulin and inhibiting glucagon secretion. Two novel antihyperglycaemic drug classes augment these effects; GLP-1 receptor agonists and inhibitors of the GLP-1 degrading enzyme dipeptidyl peptidase 4. These so called GLP-1 based or incretin based drugs are increasingly used to treat type 2 diabetes, because of a low risk of hypoglycaemia and favourable effect on body weight, blood pressure and lipid profiles. Besides glucose control, GLP-1 functions as an enterogastrone, causing a wide range of GI responses. Studies have shown that endogenous GLP-1 and its derived therapies slow down digestion by affecting the stomach, intestines, exocrine pancreas, gallbladder and liver. Understanding the GI actions of GLP-1 based therapies is clinically relevant; because GI side effects are common and need to be recognised, and because these drugs may be used to treat GI disease.
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http://dx.doi.org/10.1136/gutjnl-2015-310572DOI Listing
April 2016