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Gut May 2018Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic...
Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
Topics: Europe; Evidence-Based Practice; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic
PubMed: 29574408
DOI: 10.1136/gutjnl-2018-316027 -
World Journal of Gastroenterology Sep 2021Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma,... (Review)
Review
Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.
Topics: Cyst Fluid; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 34629795
DOI: 10.3748/wjg.v27.i34.5700 -
Digestive Surgery 2020The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological... (Review)
Review
BACKGROUND
The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance.
METHODS
We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery.
RESULTS
The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies.
CONCLUSIONS
Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.
Topics: Humans; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 30636253
DOI: 10.1159/000496509 -
International Journal of Molecular... Nov 2021Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the... (Review)
Review
Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5-9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.
Topics: Biomarkers, Tumor; Cyst Fluid; Humans; Liquid Biopsy; Pancreatic Cyst; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Prognosis
PubMed: 34884643
DOI: 10.3390/ijms222312839 -
World Journal of Gastroenterology Feb 2022Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become... (Review)
Review
Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.
Topics: Cyst Fluid; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35317424
DOI: 10.3748/wjg.v28.i6.624 -
Clinical Gastroenterology and... Aug 2022Pancreatic cysts (PC) are an increasingly common problem facing general gastroenterologists and generalists. They can be divided into 3 groups. First, those that have no...
Pancreatic cysts (PC) are an increasingly common problem facing general gastroenterologists and generalists. They can be divided into 3 groups. First, those that have no risk of developing into pancreatic cancer, such as a pseudocyst or serous cystadenomas (SCAs). Second, mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), which are precursor lesions to high-grade dysplasia and pancreatic cancer. Third, solid cancers of the pancreas, such as neuroendocrine tumors and pancreatic adenocarcinomas, which have undergone cystic degeneration.
Topics: Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35397230
DOI: 10.1016/j.cgh.2022.03.002 -
Gastroenterology Mar 2021There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.
METHODS
CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.
RESULTS
In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.
CONCLUSION
CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
Topics: Aged; CA-19-9 Antigen; Diagnosis, Differential; Early Detection of Cancer; Feasibility Studies; Female; Healthy Volunteers; Humans; Liquid Biopsy; Male; Mass Screening; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatitis, Chronic; Sensitivity and Specificity; United States
PubMed: 33333055
DOI: 10.1053/j.gastro.2020.11.052 -
Gastroenterology Jan 2023Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been...
Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.
BACKGROUND & AIMS
Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time.
METHODS
The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens.
RESULTS
Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations.
CONCLUSIONS
PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.
Topics: Humans; Retrospective Studies; Cystadenoma, Serous; Prospective Studies; Pancreatic Neoplasms; Pancreatic Cyst; High-Throughput Nucleotide Sequencing; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Genomics; Mitogen-Activated Protein Kinases
PubMed: 36209796
DOI: 10.1053/j.gastro.2022.09.028 -
Digestive Diseases and Sciences Jul 2017
Topics: Humans; Pancreatic Cyst; Pancreatitis, Chronic
PubMed: 28523572
DOI: 10.1007/s10620-017-4613-z -
World Journal of Gastroenterology Jun 2019Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo... (Review)
Review
Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo cross-sectional imaging. Current methods for the diagnosis and risk-stratification of pancreatic cysts are suboptimal, resulting in both unnecessary surgical resection and overlooked cases of neoplasia. Accurate diagnosis is crucial for guiding how a pancreatic cyst is managed, whether with surveillance for low-risk lesions or surgical resection for high-risk lesions. This review aims to summarize the current literature on confocal endomicroscopy and cyst fluid molecular analysis for the evaluation of pancreatic cysts. These recent technologies are promising adjuncts to existing approaches with the potential to improve diagnostic accuracy and ultimately patient outcomes.
Topics: Biomarkers; Cyst Fluid; Diagnosis, Differential; Endoscopy; Humans; Intravital Microscopy; Microscopy, Confocal; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Watchful Waiting
PubMed: 31235996
DOI: 10.3748/wjg.v25.i22.2734