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BMB Reports Jul 2013microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from... (Review)
Review
microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting the 3'-untranslated region of multiple target genes. Pathogenesis results from defects in several gene sets; therefore, disease progression could be prevented using miRNAs targeting multiple genes. Moreover, recent studies suggest that miRNAs reflect the stage of the specific disease, such as carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic liver disease, pancreatic cystic disease, and ovarian cystic disease, have common processes of cyst formation in the specific organ. Specifically, epithelial cells initiate abnormal cell proliferation and apoptosis as a result of alterations to key genes. Cysts are caused by fluid accumulation in the lumen. However, the molecular mechanisms underlying cyst formation and progression remain unclear. This review aims to introduce the key miRNAs related to cyst formation, and we suggest that miRNAs could be useful biomarkers and potential therapeutic targets in several cystic diseases.
Topics: Biomarkers; Cysts; Female; Humans; Liver Diseases; MicroRNAs; Pancreatic Cyst; Polycystic Kidney Diseases; Polycystic Ovary Syndrome
PubMed: 23884099
DOI: 10.5483/bmbrep.2013.46.7.151 -
Der Pathologe Dec 2019Cytology has a key role in the step-wise diagnostic approach to pancreatic mass lesions. Brush cytology and ultrasound-guided endoscopic fine-needle aspiration provide... (Review)
Review
BACKGROUND
Cytology has a key role in the step-wise diagnostic approach to pancreatic mass lesions. Brush cytology and ultrasound-guided endoscopic fine-needle aspiration provide specimens for diagnosis prior to surgical or conservative therapy. The diagnostic system of the Papanicolaou Society of Cytopathology provides a conceptual framework for reporting these specimens. Cystic lesions represent a particular challenge in pancreatic cytology, as in many instances a purely morphological approach will not result in an adequate diagnostic interpretation. Noteworthy from a conceptual point of view is how the Papanicolaou Society System incorporates non-morphological methods: laboratory chemical (CEA >192 ng/ml) and molecular (KRAS and/or GNAS mutations) findings are part of the formal diagnostic criteria for neoplastic cysts.
RESULTS
The Bern experience shows that such an integrated approach results in a significantly increased diagnostic yield. Among 83 samples analyzed, adequate DNA could be extracted in 79 samples (95%). Next generation sequencing identified pathogenic mutations in 46 cases (58%). Of these, in 35 (76%) a neoplastic cyst could not have been diagnosed by morphology alone.
CONCLUSION
These findings illustrate a new perspective for diagnostic situations, where morphology alone does allow for a sufficient diagnostic work-up. Along this line of thinking, liquid biopsy should not be regarded as a replacement, but rather an extension of the cytology's diagnostic armamentarium, according to the principle of "doing more with less."
Topics: DNA Mutational Analysis; DNA, Neoplasm; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Mutation; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 31705231
DOI: 10.1007/s00292-019-00697-4 -
Surgery Mar 2018The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen....
BACKGROUND
The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen.
METHODS
Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed.
RESULTS
Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92.
CONCLUSION
Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts.
Topics: Adenocarcinoma; Adult; Aged; Carcinoembryonic Antigen; Cohort Studies; Cyst Fluid; Female; Glucose; Humans; Male; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Sensitivity and Specificity
PubMed: 29241991
DOI: 10.1016/j.surg.2017.09.051 -
Radiology Sep 2016Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic cysts in a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD)...
Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic cysts in a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD) compared with a control group without ADPKD that was matched for age, sex, and renal function. Materials and Methods In this HIPAA-compliant, institutional review board-approved study, all patients with ADPKD provided informed consent; for control subjects, informed consent was waived. Patients with ADPKD (n = 110) with mutations identified in PKD1 or PKD2 and control subjects without ADPKD or known pancreatic disease (n = 110) who were matched for age, sex, estimated glomerular filtration rate, and date of MR imaging examination were evaluated for pancreatic cysts by using axial and coronal single-shot fast spin-echo T2-weighted images obtained at 1.5 T. Total kidney volume and liver volume were measured. Univariate and multivariable logistic regression analyses were conducted to evaluate potential associations between collected variables and presence of pancreatic cysts among patients with ADPKD. The number, size, location, and imaging characteristics of the cysts were recorded. Results Patients with ADPKD were significantly more likely than control subjects to have at least one pancreatic cyst (40 of 110 patients [36%] vs 25 of 110 control subjects [23%]; P = .027). In a univariate analysis, pancreatic cysts were more prevalent in patients with ADPKD with mutations in PKD2 than in PKD1 (21 of 34 patients [62%] vs 19 of 76 patients [25%]; P = .0002). In a multivariable logistic regression model, PKD2 mutation locus was significantly associated with the presence of pancreatic cysts (P = .0004) and with liver volume (P = .038). Patients with ADPKD and a pancreatic cyst were 5.9 times more likely to have a PKD2 mutation than a PKD1 mutation after adjusting for age, race, sex, estimated glomerular filtration rate, liver volume, and total kidney volume. Conclusion Pancreatic cysts were more prevalent in patients with ADPKD with PKD2 mutation than in control subjects or patients with PKD1 mutation. (©) RSNA, 2016 Online supplemental material is available for this article.
Topics: Case-Control Studies; Female; Genotype; Glomerular Filtration Rate; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Pancreatic Cyst; Polycystic Kidney, Autosomal Dominant; Prevalence; Retrospective Studies; TRPP Cation Channels
PubMed: 27046073
DOI: 10.1148/radiol.2016151650 -
Gut and Liver Sep 2015Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very... (Review)
Review
Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed.
Topics: Carcinoma, Pancreatic Ductal; Cystadenoma; Early Detection of Cancer; Endosonography; Humans; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic; Prevalence
PubMed: 26343068
DOI: 10.5009/gnl15063 -
Journal of Visceral Surgery Apr 2013Incidentally discovered cystic tumors of the pancreas (CTP) are an increasingly frequent entity. It is essential to differentiate lesions whose malignant potential is... (Review)
Review
Incidentally discovered cystic tumors of the pancreas (CTP) are an increasingly frequent entity. It is essential to differentiate lesions whose malignant potential is either nil or negligible (pseudocyst, serous cystadenoma, simple cysts) from lesions with intermediate malignant potential (intraductal papillary mucinous tumor of the pancreas [IPMN] involving the secondary ducts, cystic endocrine tumor) or those with high malignant potential (mucinous cystadenoma, solid pseudopapillary tumors and IPMN involving the main pancreatic duct). The approach to defining malignant potential is based on diagnostic CT scan, magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), often complemented by EUS-guided cyst puncture for biochemical and cytological analysis of cyst fluid. Surgery for diagnostic purposes should be avoided because of its significant morbidity. For pseudocysts, simple cysts and serous cystadenomas, abstention is the general rule. Resection, preserving as much pancreatic parenchyma as possible, is the rule for IPMN involving the main pancreatic duct, mucinous cystadenomas, solid and pseudopapillary tumors, and cystic endocrine tumors. Resection is rarely indicated at the outset for IPMN involving secondary pancreatic ducts; morphologic observation is the general rule and preventive excision may be indicated secondarily. Good collaboration between surgeons, radiologists and endosonographists is necessary for optimal management of CTP.
Topics: Carcinoma, Pancreatic Ductal; Cystadenocarcinoma; Cystadenoma; Diagnosis, Differential; Endosonography; Humans; Magnetic Resonance Imaging; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatic Pseudocyst; Tomography, X-Ray Computed; Treatment Outcome; Watchful Waiting
PubMed: 23518192
DOI: 10.1016/j.jviscsurg.2013.02.003 -
Archives of Pathology & Laboratory... Jan 2020Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for... (Review)
Review
CONTEXT.—
Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery.
OBJECTIVE.—
To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics.
DATA SOURCES.—
The review and analysis of the latest literature describing pancreatic cystic lesions.
CONCLUSIONS.—
Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing.
Topics: Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 31538798
DOI: 10.5858/arpa.2019-0308-RA -
Canadian Association of Radiologists... Aug 2023Pancreatic cystic lesions (PCLs) are both common and often incidental. These encompass a range of pathologies with varying degrees of concern for malignancy. Although... (Review)
Review
Pancreatic cystic lesions (PCLs) are both common and often incidental. These encompass a range of pathologies with varying degrees of concern for malignancy. Although establishing a diagnosis is helpful for determining malignant potential, many PCLs are either too small to characterize or demonstrate nonspecific morphologic features. The most salient modalities involved in diagnosis and surveillance are magnetic resonance imaging, multidetector computerized tomography, and endoscopic ultrasound. Fine needle aspiration has a role in conjunction with molecular markers as a diagnostic tool, particularly for identifying malignant lesions. Although several major consensus guidelines exist internationally, there remains uncertainty in establishing the strength of the association between all PCLs and pancreatic adenocarcinoma, and in showing a benefit from extended periods of imaging surveillance. No consensus exists between the major guidelines, particularly regarding surveillance duration, frequency, or endpoints. This review paper discusses PCL subtypes, diagnosis, and compares the major consensus guidelines with considerations for local adaptability along with questions regarding current and future priorities for research.
Topics: Humans; Pancreatic Neoplasms; Pancreatic Cyst; Adenocarcinoma; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Pancreas
PubMed: 36220377
DOI: 10.1177/08465371221130524 -
Cells Aug 2022The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic... (Review)
Review
The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or "sentinel value". In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation "panels" in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses.
Topics: Carcinoma, Pancreatic Ductal; Humans; MicroRNAs; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35954223
DOI: 10.3390/cells11152374 -
Archives of Pathology & Laboratory... Mar 2022Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic...
CONTEXT.—
Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic ultrasound/computed tomography/magnetic resonance imaging-guided fine-needle aspiration biopsies from these lesions have become an integral part of pathologists' daily practice. Because patient management has become increasingly conservative, accurate preoperative diagnosis is critical. Cytologic distinction of low-risk (pseudocysts, serous cystadenoma, lymphoepithelial cysts, and squamoid cysts of the pancreatic duct) from high-risk pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) requires incorporation of clinical, radiologic, and cytologic findings, in conjunction with chemical and molecular analysis of cyst fluid. Cytopathologists must ensure appropriate specimen triage, along with cytologic interpretation, cyst classification, and even grading of some (mucinous) cysts. Epithelial atypia in mucinous cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) has transitioned from a 3-tiered to a 2-tiered classification system, and intraductal oncocytic papillary neoplasms and intraductal tubulopapillary neoplasms have been separately reclassified because of their distinctive clinicopathologic characteristics. Because these lesions may be sampled on brushing or fine-needle aspiration biopsy, knowledge of their cytomorphology is critical.
OBJECTIVE.—
To use an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions (incorporating clinical, radiologic, and cytologic findings with [chemical/molecular] cyst fluid analysis and ancillary stains) for definitive diagnosis and classification.
DATA SOURCES.—
Review of current literature on the cytopathology of cystic/intraductal pancreatobiliary tract lesions.
CONCLUSIONS.—
Our knowledge/understanding of recent updates in cystic/intraductal pancreatobiliary lesions can ensure that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate the studies into reporting.
Topics: Cystadenoma, Serous; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Magnetic Resonance Imaging; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 33836534
DOI: 10.5858/arpa.2020-0553-RA