Publications by authors named "Iris J M Levink"

5 Publications

  • Page 1 of 1

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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April 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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December 2020

Barrett's Epithelial Thickness, Assessed by Volumetric Laser Endomicroscopy, Is Associated With Response to Radiofrequency Ablation.

Clin Gastroenterol Hepatol 2020 May 17. Epub 2020 May 17.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.

Background & Aims: Radiofrequency ablation (RFA) is the most common treatment for flat Barrett's esophagus (BE), but reasons for varying outcomes are poorly understood. A recently developed contrast-enhancement algorithm allows reliable measurement of Barrett's epithelial thickness (BET) from volumetric laser endomicroscopy (VLE) images and correlation with response to RFA. Using this algorithm, we investigated whether patients with thicker Barrett's mucosa are less likely to respond to RFA. In the future, this algorithm may guide choice of RFA dosing or endoscopic resection.

Methods: We performed a retrospective analysis on all patients with BE who received a baseline VLE scan between May 2015 and October 2016, followed by RFA and 1 follow-up exam, from 14 institutions participating in the United States VLE registry. We measured BET on equidistant locations by estimating the distance between the esophageal surface and the superficial edge of the deepest lamina propria. The primary outcome variable was the percentage reduction in Prague length; secondary outcome variables were complete remission of intestinal metaplasia (CRIM) and presence of strictures after 12 months.

Results: Images from 61 patients were included in our final analysis. Mean BET per patient ranged from 224 μm to 705 μm. A 100 μm thicker mean BET per patient resulted in a 12% lower response to treatment, measured by a reduction of Prague length (P = .03), after adjustment for confounders. We found an association between mean BET and CRIM, but not with stricture formation.

Conclusions: Based on measurements on contrast-enhanced VLE images, we found that BET correlates with response to RFA. For clinical implementation, larger studies with a standardized follow-up and development of computer-aided image analysis systems are needed.
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May 2020

HHLA2 is expressed in pancreatic and ampullary cancers and increased expression is associated with better post-surgical prognosis.

Br J Cancer 2020 04 19;122(8):1211-1218. Epub 2020 Feb 19.

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

Background: HHLA2 is a recently discovered member of the B7-family of immune checkpoint molecules with limited expression in normal tissues but overexpression in several types of cancer. The aim was to determine the expression, prevalence and biological relevance of HHLA2 protein expression in two closely related human cancer types, namely pancreatic cancer and ampullary cancer.

Methods: HHLA2 expression levels were retrospectively determined by immunohistochemistry in tissue micro-arrays of surgically resected tumours of 122 pancreatic cancer patients and 72 patients with ampullary cancer of the pancreato-biliary subtype.

Results: HHLA2 was expressed at variable levels by tumour cells in 67% of pancreatic tumours and 93% of ampullary tumours. In the combined cohort high tumoural HHLA2 expression levels were significantly associated with delayed cancer recurrence and improved post-operative cancer-specific survival. The association of HHLA2 expression with cancer-specific survival and recurrence was statistically significant for the pancreatic cancer subgroup while a similar trend was found for the ampullary cancer subgroup. In multivariable analysis together with clinicopathologic characteristics, higher HHLA2 expression was an independent predictor of cancer-specific survival.

Conclusion: The wide expression of HHLA2 in tumour cells and its association with cancer recurrence and patient survival suggest that HHLA2 represents a relevant immune checkpoint molecule in pancreatic and ampullary cancers.
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April 2020

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

Endoscopy 2018 11 18;50(11):1089-1094. Epub 2018 Jun 18.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.

Background: Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts.

Methods: Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.

Results: 25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.

Conclusions: VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo.
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November 2018