BackgroundThe diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation... Show moreBackgroundThe diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.Methods In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively.Results In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%.Interpretation This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan. Show less
CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of... Show moreCDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC. Show less
