Search

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.)

Background: Pathogenic variants in the CDKN2A 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 CDKN2A 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- Leiden , 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 CDKN2A 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., Competing Interests: Competing interests: DLC is a consultant to Tramedico. MJB received research funding from Boston Scientific, Cook Medical, and Pentax Medical. He is a consultant to Boston Scientific, Cook Medical, Pentax Medical and Mylan. The other authors have no potential competing interests to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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.

Background/objectives: In chronic pancreatitis, malabsorption of fat is common due to loss of exocrine function. Consequently, these patients are at risk to acquire deficiencies of the fat-soluble vitamins, which may result in a decreased bone mineral density (BMD) and the development of osteopenia and osteoporosis., Methods: We prospectively enrolled all patients diagnosed with chronic pancreatitis, who visited our outpatient clinic between March and November 2011. Data were collected regarding demographic characteristics, symptoms, and pancreatic function. Serum concentrations of vitamins A, E, K, and D were determined, and BMD was assessed by means of bone densitometry. Results were analyzed according to pancreatic function status and enzyme use, and compared to reference data, when available., Results: Forty patients were included (43% female; mean age of 52). Alcohol abuse was the major cause of pancreatitis (50%). Twenty-eight patients were exocrine insufficient (70%), of whom 19 used pancreatic enzymes. Vitamin A, D, E, and K deficiencies were present in 3, 53, 10, and 63% of patients, respectively. Osteopenia and osteoporosis were observed in 45% and 10% of patients. A decreased BMD was more frequently observed than expected, based on reference data, even in exocrine sufficient patients., Conclusions: Deficiencies of fat-soluble vitamins and a decreased BMD are frequently present in chronic pancreatitis, even in exocrine sufficient patients. Consequently, all patients with chronic pancreatitis should be routinely screened for fat-soluble vitamin deficiencies and a decreased BMD., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: After pancreatic surgery, up to 80 % of patients will develop exocrine insufficiency. For enzyme supplementation to be effective, prescribing an adequate dose of pancreatic enzymes is mandatory but challenging because the required dose varies. Data on the practice of enzyme replacement therapy after surgery are lacking, and therefore, we conducted this analysis., Methods: An anonymous survey was distributed to members of the Dutch and German patient associations for pancreatic disorders. The target population consisted of patients with chronic pancreatitis or pancreatic cancer who had undergone pancreatic surgery and were using enzymes to treat exocrine insufficiency. Results were compared to a similar group of non-operated patients., Results: Ninety-one cases were analyzed (84 % underwent a resection procedure). The median daily enzyme dose was 6, and 25 % took three or less capsules. Despite treatment, 68 % of patients reported steatorrhea-related symptoms, 48 % adhered to a non-indicated dietary fat restriction, and only 33 % had visited a dietician. The outcome was equally poor for the 91 non-operated patients., Conclusion: Most patients suffering from exocrine insufficiency after pancreatic surgery are undertreated. To improve efficacy, physicians should be more focused on treating exocrine insufficiency and educate patients to adjust the dose according to symptoms and their diet.

Background: Comprehensive monitoring of colonoscopy quality requires complete and accurate colonoscopy reporting., Objective: This study aimed to assess the compliance with colonoscopy reporting and to assess the quality of colonoscopy performance., Design: Consecutive colonoscopy reports were reviewed by hand. Four hundred reports were included from each department., Setting: Daily clinical practice in 12 Dutch endoscopy departments., Patients: Consecutive patients undergoing scheduled colonoscopy procedures., Main Outcome Measurements: Quality of reporting was assessed by using the American Society for Gastrointestinal Endoscopy criteria for colonoscopy reporting. Quality of colonoscopy performance was evaluated by using the cecal intubation rate and adenoma detection rate (ADR)., Results: A total of 4800 colonoscopies were performed by 116 endoscopists: 70% by gastroenterologists, 16% by gastroenterology fellows, 10% by internists, 3% by nurse-endoscopists, and 1% by surgeons. The mean age of the patients was 59 years (standard deviation 16), and 47% were male. Reports contained information on indication, sedation practice, and extent of the procedure in more than 90%. Only 62% of the reports mentioned the quality of bowel preparation (range between departments 7%-100%); photographic documentation of the cecal landmarks was present in 71% (range 22%-97%). The adjusted cecal intubation rate was 92% (range 84%-97%). The ADR was 24% (range 13%-32%)., Limitations: Dependent on reports, no intervention in endoscopic practice. No analysis for performance per endoscopist., Conclusion: Colonoscopy reporting varied significantly in clinical practice. Colonoscopy performance met the suggested standards; however, considerable variability between endoscopy departments was found. The results of this study underline the importance of the implementation of quality indicators and guidelines. Moreover, by continuous monitoring of quality parameters, the quality of both colonoscopy reporting and colonoscopy performance can easily be improved., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Treating exocrine pancreatic insufficiency with pancreatic enzymes is challenging because there is no fixed dose regimen. The required dose varies per patient, depending on the residual pancreatic function, the gut lumen physiology, and the fat content of each meal. Using a sufficient dose of enzymes is crucial to prevent weight loss, nutritional deficiencies, and to ameliorate steatorrhea-related symptoms. Data regarding the practise of enzyme replacement therapy are lacking. Therefore, we evaluated if patients with exocrine insufficiency caused by chronic pancreatitis receive proper treatment in the Netherlands., Methods: An anonymous survey was distributed to the members of the Dutch Association of Patients with Pancreatic Disorders. The survey focused on enzyme use, steatorrhea-related symptoms, dietary consultation, and food restrictions. Responding patients were included if they had chronic pancreatitis and were treated for exocrine insufficiency with pancreatic enzymes., Results: The survey was returned by 178 members who suffered from chronic pancreatitis, 161 of whom (90%) met the inclusion criteria. The mean age was 56 years and 53% were male. The median enzyme intake was 6 capsules per day and 25% of patients took 3 or less capsules. Remarkably, 70% of patients still reported steatorrhea-related symptoms, despite treatment. Only 25% of cases were referred to a dietician and 58% kept a restriction of fat (either instructed by a dietician or self-imposed)., Conclusion: Many patients with exocrine insufficiency caused by chronic pancreatitis are under-treated in the Netherlands, a country with a well-organized healthcare system. To improve treatment efficacy, patients should be educated in adjusting the enzyme dosage according to steatorrhea-related symptoms and dietary fat intake. Moreover, patients should be referred to a well-trained, specialized dietician., (Copyright © 2012 Elsevier Ltd. All rights reserved.)