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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 -
World Journal of Gastroenterology Jun 2021Cystic pancreatic lesions involve a wide variety of pathological entities that include neoplastic and non-neoplastic lesions. The proper diagnosis, differentiation, and...
Cystic pancreatic lesions involve a wide variety of pathological entities that include neoplastic and non-neoplastic lesions. The proper diagnosis, differentiation, and staging of these cystic lesions are considered a crucial issue in planning further management. There are great challenges for their diagnostic models. In our time, new emerging methods for this diagnosis have been discovered. Endoscopic ultrasonography-guided fine-needle aspiration cytology with chemical and molecular analysis of cyst fluid and EUS-guided fine needle-based confocal laser endomicroscopy, through the needle microforceps biopsy, and single-operator cholangioscopy/pancreatoscopy are promising methods that have been used in the diagnosis of cystic pancreatic lesions. Hereby we discuss the diagnosis of cystic pancreatic lesions and the benefits of various diagnostic models.
Topics: Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 34135548
DOI: 10.3748/wjg.v27.i21.2664 -
BMJ Case Reports Oct 2020A 60-year-old woman was investigated for abdominal pain and increasing asthenia. Abdominal CT revealed a 25 mm hypodense cystic lesion in the tail of the pancreas. MRI...
A 60-year-old woman was investigated for abdominal pain and increasing asthenia. Abdominal CT revealed a 25 mm hypodense cystic lesion in the tail of the pancreas. MRI showed a multiloculated cystic lesion, T1-hypointense and T2-hyperintense lesion, without wall enhancement. Endoscopic ultrasound detected a 25 mm multi-loculated cystic lesion, with regular margin and without pancreatic duct communication. Diagnosis of pancreatic mucinous cystadenoma was discussed and the patient was referred to surgery. She underwent distal pancreatectomy with spleen preservation. Pathological examination revealed the diagnosis of pancreatic mesothelial cyst. Histologically, the cyst was multiloculated, lined by cuboidal epithelium, ovoid nuclei and amphophilic cytoplasm, without mucin deposition or cytological atypia. Immunohistochemistry examination revealed positive staining for cytokeratin 5/6, vimentin and calretinin. At 1-year follow-up, she is in her usual health, without any symptoms.
Topics: Cystadenoma, Mucinous; Diagnosis, Differential; Endosonography; Epithelium; Female; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Middle Aged; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33028569
DOI: 10.1136/bcr-2020-236255 -
Revista Espanola de Enfermedades... Jun 2020Pancreatic fluid collections frequently occur in the context of moderate and severe acute pancreatitis, and may also appear as a complication of chronic pancreatitis,... (Review)
Review
Pancreatic fluid collections frequently occur in the context of moderate and severe acute pancreatitis, and may also appear as a complication of chronic pancreatitis, pancreatic surgery or trauma. It is essential to adhere to the Atlanta classification nomenclature that subclassifies them into four categories (acute peripancreatic fluid collections, acute necrotic collections, pseudocysts, and walled-off necrosis) since it has an impact on prognosis and management. Pseudocysts and walled-off pancreatic necrosis are encapsulated pancreatic fluid collections characterized by a surrounding inflammatory wall, which typically develops three to four weeks after the onset of acute pancreatitis. Most pancreatic fluid collections resolve spontaneously and do not require intervention. However, when they become symptomatic or complicated drainage is indicated, and endoscopic ultrasound-guided drainage has become first-line treatment of encapsulated collections. Drainage of pseudocysts is relatively straightforward due to their liquid content. However, in walled-off necrosis the presence of solid necrotic debris can make treatment more challenging and therefore multidisciplinary management in experienced centers is recommended, being a step-up approach the current standard of care. In this review, we aim to address the management of pancreatic fluid collections with an especial focus on endoscopic drainage.
Topics: Acute Disease; Drainage; Humans; Pancreatic Pseudocyst; Pancreatitis, Acute Necrotizing
PubMed: 32450706
DOI: 10.17235/reed.2020.6814/2019 -
Digestive Diseases and Sciences May 2022Andrew Canakis. (Review)
Review
Andrew Canakis.
Topics: Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 34383196
DOI: 10.1007/s10620-021-07084-1 -
Surgical Oncology Clinics of North... Oct 2021Pancreatic cancer is the third leading cause of cancer death in the United States, with a 5-year survival rate of 9%. Individuals with inherited pancreatic cancer... (Review)
Review
Pancreatic cancer is the third leading cause of cancer death in the United States, with a 5-year survival rate of 9%. Individuals with inherited pancreatic cancer syndromes are at an increased risk for developing pancreatic cancer and may benefit from pancreatic cancer surveillance with the goal to detect and intervene on early-stage cancer or high-risk precursor lesions. Given the screening implications for family members and therapeutic implications for probands, all patients diagnosed with pancreatic cancer are recommended to undergo germline genetic testing.
Topics: Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Neoplastic Syndromes, Hereditary; Pancreas; Pancreatic Neoplasms; Risk Factors; United States
PubMed: 34511196
DOI: 10.1016/j.soc.2021.06.002 -
Cancers Apr 2023Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of... (Review)
Review
Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of reliable screening and diagnostic options for early detection. Amongst known pre-malignant pancreatic lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent. The current standard of care for the diagnosis and classification of pancreatic cystic lesions (PCLs) involves cross-sectional imaging studies and endoscopic ultrasound (EUS) and, when indicated, EUS-guided fine needle aspiration and cyst fluid analysis. However, this is suboptimal for the identification and risk stratification of PCLs, with accuracy of only 65-75% for detecting mucinous PCLs. Artificial intelligence (AI) is a promising tool that has been applied to improve accuracy in screening for solid tumors, including breast, lung, cervical, and colon cancer. More recently, it has shown promise in diagnosing pancreatic cancer by identifying high-risk populations, risk-stratifying premalignant lesions, and predicting the progression of IPMNs to adenocarcinoma. This review summarizes the available literature on artificial intelligence in the screening and prognostication of precancerous lesions in the pancreas, and streamlining the diagnosis of pancreatic cancer.
PubMed: 37173876
DOI: 10.3390/cancers15092410