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United European Gastroenterology Journal Sep 2023Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative...
BACKGROUND
Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population.
METHODS
The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months.
RESULTS
Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03).
CONCLUSIONS
In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.
Topics: Humans; Female; Aged; Male; Prospective Studies; CA-19-9 Antigen; Pancreatic Neoplasms; Pancreatic Cyst
PubMed: 37435855
DOI: 10.1002/ueg2.12422 -
Gastroenterology Dec 2023Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course...
BACKGROUND & AIMS
Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening.
METHODS
A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration).
RESULTS
Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm.
CONCLUSIONS
Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.
Topics: Humans; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Hyperplasia; Carcinoma in Situ; Adenocarcinoma
PubMed: 37633497
DOI: 10.1053/j.gastro.2023.08.027 -
Scientific Reports Nov 2023Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are...
Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.
Topics: Humans; Biomarkers; MicroRNAs; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 37963969
DOI: 10.1038/s41598-023-47129-1 -
Machine Learning in Medical Imaging.... Oct 2023Intraductal Papillary Mucinous Neoplasm (IPMN) cysts are pre-malignant pancreas lesions, and they can progress into pancreatic cancer. Therefore, detecting and...
Intraductal Papillary Mucinous Neoplasm (IPMN) cysts are pre-malignant pancreas lesions, and they can progress into pancreatic cancer. Therefore, detecting and stratifying their risk level is of ultimate importance for effective treatment planning and disease control. However, this is a highly challenging task because of the diverse and irregular shape, texture, and size of the IPMN cysts as well as the pancreas. In this study, we propose a novel computer-aided diagnosis pipeline for IPMN risk classification from multi-contrast MRI scans. Our proposed analysis framework includes an efficient volumetric self-adapting segmentation strategy for pancreas delineation, followed by a newly designed deep learning-based classification scheme with a radiomics-based predictive approach. We test our proposed decision-fusion model in multi-center data sets of 246 multi-contrast MRI scans and obtain superior performance to the state of the art (SOTA) in this field. Our ablation studies demonstrate the significance of both radiomics and deep learning modules for achieving the new SOTA performance compared to international guidelines and published studies (81.9% vs 61.3% in accuracy). Our findings have important implications for clinical decision-making. In a series of rigorous experiments on multi-center data sets (246 MRI scans from five centers), we achieved unprecedented performance (81.9% accuracy). The code is available upon publication.
PubMed: 38274402
DOI: 10.1007/978-3-031-45676-3_14 -
GE Portuguese Journal of... Sep 2023The transcendence of endoscopic ultrasound (EUS) from diagnostic to therapeutic tool has revolutionized management options in the field of gastroenterology. Through... (Review)
Review
The transcendence of endoscopic ultrasound (EUS) from diagnostic to therapeutic tool has revolutionized management options in the field of gastroenterology. Through EUS-guided methods, pancreaticobiliary obstruction can now be utilized as an alternative to surgical and percutaneous approaches. This modality also allows for gallbladder drainage in patients who are not ideal operative candidates. By utilizing its unique imaging capabilities, EUS also allows for drainage access points in cases of gastric outlet obstruction as well as windows to ablate pancreatic cystic lesions. As technical progress continues to evolve, interventional gastroenterology continues to push the envelope of minimally invasive therapeutic procedures in a multidisciplinary setting. In this comprehensive review, we set out to describe current indications and innovations through EUS.
PubMed: 37818395
DOI: 10.1159/000529089 -
Korean Journal of Radiology Jun 2024Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic... (Review)
Review
Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic lesions, determining when to recommend aggressive actions such as surgical resection or endoscopic ultrasound with sampling is difficult. In this article, we review the common types of cystic pancreatic lesions including serous cystadenoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm with imaging examples of each. We also discuss high-risk or worrisome imaging features that warrant a referral to a surgeon or endoscopist and provid several examples of these features. These imaging features adhere to the latest guidelines from the International Consensus Guidelines, American Gastroenterological Association (2015), American College of Gastroenterology (2018), American College of Radiology (2010, 2017), and European Guidelines (2013, 2018). Our focused article addresses the imaging dilemma of managing incidental cystic pancreatic lesions, weighing the options between imaging follow-up and aggressive interventions.
Topics: Humans; Pancreatic Cyst; Incidental Findings; Pancreatic Neoplasms; Diagnosis, Differential; Pancreas; Tomography, X-Ray Computed
PubMed: 38807337
DOI: 10.3348/kjr.2024.0085 -
BioRxiv : the Preprint Server For... Sep 2023The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar...
The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas tissue homeostasis are poorly understood. Here, we evaluate the role of Par3 in acinar pancreas injury and homeostasis. While Par3 loss in the mouse pancreas disrupts tight junctions, Par3 loss is dispensable for pancreatogenesis. However, with aging, Par3 loss results in low-grade inflammation, acinar degeneration, and pancreatic lipomatosis. Par3 loss also exacerbates pancreatitis-induced acinar cell loss, resulting in pronounced pancreatic lipomatosis and failure to regenerate. Moreover, Par3 loss in mice harboring mutant Kras causes extensive pancreatic intraepithelial neoplastic (PanIN) lesions and large pancreatic cysts. We also show that Par3 loss restricts injury-induced primary ciliogenesis. Significantly, targeting BET proteins enhances primary ciliogenesis during pancreatitis-induced injury and, in mice with Par3 loss, limits pancreatitis-induced acinar loss and facilitates acinar cell regeneration. Combined, this study demonstrates how Par3 restrains pancreatitis- and Kras-induced changes in the pancreas and identifies a potential role for BET inhibitors to attenuate pancreas injury and facilitate pancreas tissue regeneration.
PubMed: 37745543
DOI: 10.1101/2023.09.14.557654 -
Journal of Clinical Medicine Jul 2023Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the... (Review)
Review
Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the latest advancements in endosonography of the pancreas, focusing on key technological developments, procedural techniques, clinical applications and additional techniques, which include real-time elastography endoscopic ultrasound, contrast-enhanced-EUS, EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. EUS is well established for T-staging and N-staging of pancreaticobiliary malignancies, for pancreatic cyst discovery, for identifying subepithelial lesions (SEL), for differentiation of benign pancreaticobiliary disorders or for acquisition of tissue by EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. This review briefly describes principles and application of EUS and its related techniques.
PubMed: 37510744
DOI: 10.3390/jcm12144630 -
Abdominal Radiology (New York) Aug 2023This study aimed to characterize the clinical and imaging findings of intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) compared to those of intraductal...
PURPOSE
This study aimed to characterize the clinical and imaging findings of intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) compared to those of intraductal papillary mucinous adenoma/carcinoma (IPMA/IPMC).
METHODS
This multi-institutional retrospective study reviewed the clinical, imaging, and pathological findings of 21 patients with pathologically proven IOPN-P. Twenty-one computed tomography (CT) and magnetic resonance imaging, and seven F-fluorodeoxyglucose (FDG)-positron emission tomography were performed before surgery. The following findings were evaluated: preoperative blood test results, lesion size and location, pancreatic duct diameter, contrast-enhancement effect, bile duct and peripancreatic invasion, maximum standardized uptake (SUVmax) value, and pathological stromal invasion.
RESULTS
Serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9) levels were significantly higher in the IPMN/IPMC group than in the IOPN-P group. Except in one patient, IOPN-P showed multifocal cystic lesions with solid components or a tumor in the main pancreatic duct (MPD) with dilatation. IOPN-P had a higher frequency of solid parts and a lower frequency of downstream MPD dilatation than IPMA. IPMC showed smaller overall cyst size, more radiological peripancreatic invasion, and worse recurrence-free and overall survival than IOPN-P. The average SUVmax value of IOPN-P was 7.5. Pathologically, 17 of the 21 IOPN-Ps had a malignant component, and six showed stromal invasion.
CONCLUSION
IOPN-P shows cystic-solid lesions similar to IPMC but has lower serum CEA and CA19-9 levels, larger overall cyst size, lower frequency of peripancreatic invasion, and more favorable prognosis than IPMC. Moreover, the high FDG uptake by IOPN-Ps may be a characteristic finding of this study.
Topics: Humans; Carcinoma, Pancreatic Ductal; Retrospective Studies; Fluorodeoxyglucose F18; Carcinoembryonic Antigen; CA-19-9 Antigen; Pancreatic Neoplasms; Pancreas; Cysts; Neoplasm Invasiveness
PubMed: 37358603
DOI: 10.1007/s00261-023-03985-z