Chang “Hsa-miR-96 and hsa-miR-217 Expression Down Regulates with Increasing Dysplasia in Pancreatic Intraepithelial Neoplasias (PanINs) and Intraductal Papillary Mucinous Neoplasms” 8 de abril de 2017 OS miRNAs têm funções oncogénicas ou de supressores tumorais. O hsa-miR- 96 e has-miR-217 têm como alvo a proteína
KRAS, cujo gene é o único mutado em ambos PanINs e IPMNs. Deste modo, escolheram-se estes dois miRs como objeto de estudo. Foi analisada a sua expressão em lesões pré-malignas (IPMNs e PanINs), bem como em PDACs De um grupo de doentes submetidos a pancreatectomia foi selecionada a seguinte amostra de peças cirúrgicas: 45 PDACs, 58 PanINs e 57 IPMNs. Destes últimos: 13 IPMNs baixo grau; 11 de grau intermédio; 7 de alto grau; 26 IPMNs com carcinoma invasivo associado.
Todas as peças foram analisadas de acordo com a classificação da WHO 2010.
Resultados da técnica LNA-ISH foram
classificados com base na intensidade da
hibridização dos miRs em 0 (expressão ausente ou fraca), 1 (expressão moderada e 2 (forte expressão). Cada um destes scores corresponde a uma % de células com evidencia positiva da presença de miRs hibridizados.
Verificou-se que com o aumento do grau dos PanINs a expressão de hsa-miR-96 e hsa-miR-217 tende a reduzir. No PaIN3 a expressão destes miRs foi muito semelhante à dos PDACs, indicando um padrão de expressão de miR semelhantes entre as duas lesões. A expressão de hsa-miR-96 e hsa-miR-217 reduziu com o aumento do grau dos IPMNs. Contudo, não houve diferenças estatisticamente significativas entre os diferentes graus (baixo, intermédio e moderado). Apenas no IPMN associado a carcinoma invasivo a diferença de expressão de hsa-miR-96 foi considerada significativa, o que sugere que este pode ser um potencial marcador para distinguir lesões benignas de malignas antes da cirurgia. Comparando a expressão de hsa-miR-96 e hsa-miR- 217 entre PaINs e IPMNs, com o mesmo grau de proliferação epitelial, não se verificaram diferenças significativas. Assim, levanta-se a hipótese de que a expressão destas moléculas pode relacionar-se mais com o grau de atipia do que com o tipo histológico da lesão.
53 Tabela XXV - Wang et al. MicroRNA expression levels as diagnostic biomarkers for intraductal papillary mucinous neoplasm
1º AUTOR TÍTULO E ANO OBJETIVOS AMOSTRAS DESIGN DO ESTUDO RESULTADOS IMPORTANTES
Lei Wang “MicroRNA
expression levels as diagnostic biomarkers for intraductal papillary mucinous neoplasm” 8 de maio de 2017 Neste estudo, avaliou-se a expressão diferencial de miRNAs entre IPMNs benignos e malignos e identificaram-se vários miRNAs que podem servir como marcadores de diagnóstico para IPMNs malignos. Amostras de tecidos pancreáticos FFEP de 78 casos de doentes com IPMN: 38 benignos e 40 malignos. Utilizou-se uma amostra de controlos com tecidos pancreáticos normais cuja informação não consta no texto.
As amostras de tecido foram classificadas segundo os critérios da WHO.
Estas foram testadas para diferentes biomarcadores incluindo: proteínas séricas totais (TP), albumina (Alb), bilirrubina total (T-Bil), alanina transferase (ALT), aspartato transferase (AST) e o marcador tumoral CA19-9. No pós-operatório mediram-se os níveis séricos de ALP, glutamiltransferase (GTP), amilase e CEA.
MiRNA foram isolados das amostras em FFEP usando kits apropriados e a sua expressão foi analisada através de métodos com RT-PCR. Foram analisados 15 miRs (selecionados da literatura) potencialmente desregulados em IPMNs vs controlos e o perfil destes em diferentes lesões pancreáticas.
Verificou-se que apenas os níveis de T-Bil e o CA19-9 foram significativamente diferentes entre amostras malignas e benignas. Os outros biomarcadores não mostraram níveis diferentes entre as lesões, o que sugere que os marcadores tumorais mais conhecidos não são efetivos para o diagnóstico de IPMNs. 9 Mirs (miR-100, miR-107, miR-215, miR-21, miR- 221, miR-155, miR-187, miR-210 e miR-223) são diferentemente expressos entre IPMNs e controlos, todos eles suprarregulados, o que sugere que estes podem ter um papel na promoção da patogénese dos IPMNs e podem ser marcadores específicos destas lesões.
Constatou-se que 4 miRs (miR-100, miR-187, miR- 210, miR-223) estavam suprarregulados nos subtipos de IPMN de pior prognóstico (pancreático- biliar e Oncocítico) comparando com os subtipos de melhor prognóstico (gástrico e intestinal). Isto sugere que a expressão destes miRNAs pode ser associada ao status de prognóstico dos IPMNs. Os miR-21, miR-155, miR-187, miR-210 e miR-223 estavam significativamente mais expressos em IPMNs do que nas amostras pancreatite.
Comparando IPMN com PDAC os miR-16, miR-17, miR-181a e miR-187, estão diferentemente expressos.
Estes resultados sugerem que os miRNAs
diferentemente expressos entre amostras de IPMN, pancreatite crónica e PDAC podem servir de novos marcadores diagnósticos para diferentes doenças pancreáticas.
54 Tabela XXVI - Goto et al. An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker
1º AUTOR TÍTULO E ANO OBJETIVOS AMOSTRAS DESIGN DO ESTUDO RESULTADOS IMPORTANTES
Goto, T. “An elevated
expression of serum exosomal microRNA-191, -21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker” 31 de Janeiro 2018
Foi relatado que os miRNAs se encontram estavelmente contidos dentro de pequenas vesículas (exosomas), segregadas pelas células, para interagir com tecidos
distantes. Podem ser encontradas em todos os fluídos corporais, incluindo linfa e plasma. Os miRNAs em exosomas (ExmiRs) são estabilizados pela RNase, e são muito mais ricos no soro do que miRs livres. A expressão dos ExmiRs foi analisada em doentes com IPMN e PDAC. 32 doentes diagnosticados com PDAC; 29 com IPMN; 22 controlos. Amostras de sangue periférico obtidas antes dos tratamentos (cirurgia, quimio ou radioterapia) Todos os doentes realizaram TC toracoabdominal para estadiamento do tumor de acordo com os critérios TMN ou com as guidelines. Foi realizada isolação de ExmiRs das amostras por técnicas de precipitação e extração de RNA por kit apropriado. A avaliação da quantidade e qualidade do RNA foi feita por
espectrometria. A seleção dos miRs para estudo foi feita
analisando amostras de 5 doentes aleatórios para análise da expressão de ExmiRs por Next
Generation Sequencer
(NGS). Os dados da sequenciação foram mapeados numa análise de expressão e
sequenciação de miRs. A quantificação de miRs selecionados foi feita por RT-qPCR.
Dentro dos 347 ExmiRs detetados, a expressão de ExmiR-191, ExmiR-21 e ExmiR-451a estava significativamente aumentada nos grupos IPMN e PDAC. A acuidade diagnóstica, sensibilidade e especificidade dos ExmiRs foi superior aos dos respetivos CmiR (miR circulante livre no plasma) no diagnóstico de IPMN e PC.
O ExmiR-21 mostrou a maior acuidade diagnóstica para IPMN = 78.0%, e para PDAC = 80.8%.
A expressão de ExmiR-451a foi maior nos doentes com IPMN e com nódulos murais do que nos sem nódulos. ExmiR-451a pode estar fortemente associado à progressão maligna de IPMN. A sobrevida global no grupo de alta expressão de ExmiR-21 foi significativamente mais curta que no grupo de baixa expressão deste ExmiR.
ExmiR-191 e ExmiR-451a não afetam a sobrevida nos doentes com PC.
ExmiR-21 e ExmiR-451a mostraram-se mais expressos em doentes com doença progressiva, do que naqueles com resposta completa ou parcial, ou doença estável. Isto sugere que ExmiR-21 e ExmiR- 451a reduzem a taxa de controlo da doença no PC. Enquanto os marcadores CEA e CA1-9 só se encontraram elevados apenas em tumores avançados, os ExmiRs estavam suprarregulados tanto em PDAC como em IPMNs e obtiveram melhor performance diagnóstica que os marcadores tumorais, sugerindo que os ExmiR-191, ExmiR-21, e ExmiR-451a podem servir de marcadores
55
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IBLIOGRAFIA1. Del Chiaro M, Verbeke C, Salvia R, et al. European experts consensus statement on cystic tumours of the pancreas. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Sep 2013;45(9):703-711.
2. Vege SS, Ziring B, Jain R, et al. American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts. Gastroenterology.148(4):819-822.
3. Asif Khalid KM. Classification of Pancreatic cysts. 2017;
https://www.uptodate.com/contents/classification-of-pancreatic-
cysts?source=search_result&search=cistos+pancre%C3%A1ticos&selectedTitle=1%7E8 9. Accessed Outubro, 2017.
4. Brugge WR, Lauwers GY, Sahani D, Fernandez-del Castillo C, Warshaw AL. Cystic neoplasms of the pancreas. The New England journal of medicine. Sep 16 2004;351(12):1218-1226.
5. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. May-Jun 2012;12(3):183-197.
6. Utomo WK, Looijenga LH, Bruno MJ, et al. A MicroRNA Panel in Pancreatic Cyst Fluid for the Risk Stratification of Pancreatic Cysts in a Prospective Cohort. Molecular therapy. Nucleic acids. 2016;5:e350.
7. Hines OJ, Reber HA. Pancreatic surgery. Current opinion in gastroenterology. Sep 2009;25(5):460-465.
8. Basar O, Brugge WR. Pancreatic cyst guidelines: Which one to live by? Gastrointestinal Endoscopy.85(5):1032-1035.
9. Utomo WK, Braat H, Bruno MJ, et al. Cytopathological Analysis of Cyst Fluid Enhances Diagnostic Accuracy of Mucinous Pancreatic Cystic Neoplasms. Medicine. Jun
2015;94(24):e988.
10. Goh BK, Tan DM, Thng CH, et al. Are the Sendai and Fukuoka consensus guidelines for cystic mucinous neoplasms of the pancreas useful in the initial triage of all suspected pancreatic cystic neoplasms? A single-institution experience with 317 surgically- treated patients. Annals of surgical oncology. Jun 2014;21(6):1919-1926.
11. Fritz S, Klauss M, Bergmann F, et al. Pancreatic main-duct involvement in branch-duct IPMNs: an underestimated risk. Annals of surgery. Nov 2014;260(5):848-855;
discussion 855-846.
12. Sahora K, Mino-Kenudson M, Brugge W, et al. Branch duct intraductal papillary mucinous neoplasms: does cyst size change the tip of the scale? A critical analysis of the revised international consensus guidelines in a large single-institutional series. Annals of surgery. Sep 2013;258(3):466-475.
13. Roch AM, Ceppa EP, DeWitt JM, et al. International Consensus Guidelines parameters for the prediction of malignancy in intraductal papillary mucinous neoplasm are not properly weighted and are not cumulative. HPB : the official journal of the
International Hepato Pancreato Biliary Association. Oct 2014;16(10):929-935.
14. Kim KW, Park SH, Pyo J, et al. Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta- analysis. Annals of surgery. Jan 2014;259(1):72-81.
15. Loosen SH, Neumann UP, Trautwein C, Roderburg C, Luedde T. Current and future biomarkers for pancreatic adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. Jun
56
16. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions:
explanation and elaboration. Journal of clinical epidemiology. Oct 2009;62(10):e1-34.
17. Whiting PF, Rutjes AS, Westwood ME, et al. Quadas-2: A revised tool for the quality assessment of diagnostic accuracy studies. Annals of Internal Medicine.
2011;155(8):529-536.
18. Wang L, Zheng J, Sun C, et al. MicroRNA expression levels as diagnostic biomarkers for intraductal papillary mucinous neoplasm. Oncotarget. Aug 29 2017;8(35):58765- 58770.
19. Nakahara O, Takamori H, Iwatsuki M, et al. Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2. Annals of surgical oncology. Jul 2012;19 Suppl 3:S565-571.
20. Jiao LR, Frampton AE, Jacob J, et al. MicroRNAs targeting oncogenes are down- regulated in pancreatic malignant transformation from benign tumors. PloS one. 2012;7(2):e32068.
21. Caponi S, Funel N, Frampton AE, et al. The good, the bad and the ugly: a tale of miR- 101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms. Annals of oncology : official journal of the European Society for Medical Oncology. Mar 2013;24(3):734-741.
22. Lubezky N, Loewenstein S, Ben-Haim M, et al. MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas. Surgery. May
2013;153(5):663-672.
23. Park M, Kim M, Hwang D, et al. Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Apr 2014;27(4):580-593.
24. Lee LS, Szafranska-Schwarzbach AE, Wylie D, et al. Investigating MicroRNA Expression Profiles in Pancreatic Cystic Neoplasms. Clinical and translational gastroenterology. Jan 30 2014;5:e47.
25. Zhang B, Guo X, Zhang J, Liu X, Zhan X, Li Z. MicroRNA224 is downregulated in mucinous cystic neoplasms of the pancreas and may regulate tumorigenesis by targeting Jagged1. Molecular medicine reports. Dec 2014;10(6):3303-3309.
26. Lahat G, Lubezky N, Loewenstein S, et al. Epithelial-to-mesenchymal transition (EMT) in intraductal papillary mucinous neoplasm (IPMN) is associated with high tumor grade and adverse outcomes. Annals of surgical oncology. Dec 2014;21 Suppl 4:S750-757.
27. Permuth-Wey J, Chen YA, Fisher K, et al. A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high- risk and low-risk intraductal papillary mucinous neoplasms of the pancreas. PloS one. 2015;10(1):e0116869.
28. Chang X, Yu C, Li J, Yu S, Chen J. hsa-miR-96 and hsa-miR-217 Expression Down- Regulates with Increasing Dysplasia in Pancreatic Intraepithelial Neoplasias and Intraductal Papillary Mucinous Neoplasms. International journal of medical sciences. 2017;14(5):412-418.
29. Komatsu S, Ichikawa D, Miyamae M, et al. Malignant potential in pancreatic neoplasm; new insights provided by circulating miR-223 in plasma. Expert opinion on biological therapy. Jun 2015;15(6):773-785.
30. Matthaei H, Wylie D, Lloyd MB, et al. miRNA biomarkers in cyst fluid augment the diagnosis and management of pancreatic cysts. Clinical cancer research : an official journal of the American Association for Cancer Research. Sep 1 2012;18(17):4713- 4724.
57
31. Ryu JK, Matthaei H, Dal Molin M, et al. Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2011;11(3):343-350.
32. Henry JC, Bassi C, Giovinazzo F, Bloomston M. MicroRNA from pancreatic duct aspirate differentiates cystic lesions of the pancreas. Annals of surgical oncology. Dec 2013;20 Suppl 3:S661-666.
33. Habbe N, Koorstra JB, Mendell JT, et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer biology & therapy. Feb 2009;8(4):340-346.
34. Frampton AE, Krell J, Prado MM, et al. Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies. Oncotarget. May 10 2016;7(19):28556-28569.
35. Goto T, Fujiya M, Konishi H, et al. An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker. BMC cancer. Jan 31 2018;18(1):116.
36. Permuth JB, Choi J, Balarunathan Y, et al. Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms. Oncotarget. Dec 27 2016;7(52):85785-85797.
37. Permuth-Wey J, Chen DT, Fulp WJ, et al. Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas. Cancer prevention research (Philadelphia, Pa.). Sep 2015;8(9):826-834.
38. Permuth JB, Chen DT, Yoder SJ, et al. Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas. Scientific reports. Sep 5 2017;7(1):10484.
39. Farrell JJ, Toste P, Wu N, et al. Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer. The American journal of
gastroenterology. Aug 2013;108(8):1352-1359.
40. Aso T, Ohtsuka T, Tamura K, et al. Elevated expression level of microRNA-196a is predictive of intestinal-type intraductal papillary mucinous neoplasm of the pancreas. Pancreas. Apr 2014;43(3):361-366.
41. Humeau M, Vignolle-Vidoni A, Sicard F, et al. Salivary MicroRNA in Pancreatic Cancer Patients. PloS one. 2015;10(6):e0130996.
42. Wang J, Paris PL, Chen J, et al. Next generation sequencing of pancreatic cyst fluid microRNAs from low grade-benign and high grade-invasive lesions. Cancer letters. Jan 28 2015;356(2 Pt B):404-409.
43. Szafranska AE, Davison TS, Shingara J, et al. Accurate molecular characterization of formalin-fixed, paraffin-embedded tissues by microRNA expression profiling. J Mol Diagn. Sep 2008;10(5):415-423.
44. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. Oct 28 2010;467(7319):1114-1117.
45. Kimura W, Nagai H, Kuroda A, Muto T, Esaki Y. Analysis of small cystic lesions of the pancreas. International journal of pancreatology : official journal of the International Association of Pancreatology. Dec 1995;18(3):197-206.
46. Schonleben F, Qiu W, Ciau NT, et al. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clinical cancer research : an official journal of the American Association for Cancer Research. Jun 15 2006;12(12):3851- 3855.
47. Sato N, Rosty C, Jansen M, et al. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. The American journal of pathology. Dec 2001;159(6):2017-2022.
48. Iacobuzio-Donahue CA, Klimstra DS, Adsay NV, et al. Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas:
58 comparison with conventional ductal adenocarcinomas. The American journal of pathology. Sep 2000;157(3):755-761.
49. Iacobuzio-Donahue CA, Wilentz RE, Argani P, et al. Dpc4 protein in mucinous cystic neoplasms of the pancreas: frequent loss of expression in invasive carcinomas
suggests a role in genetic progression. The American journal of surgical pathology. Nov 2000;24(11):1544-1548.
50. Liu CG, Calin GA, Volinia S, Croce CM. MicroRNA expression profiling using microarrays. Nature protocols. 2008;3(4):563-578.
51. Zhu W, Xu B. MicroRNA-21 Identified as Predictor of Cancer Outcome: A Meta- Analysis. PloS one. 2014;9(8):e103373.
52. Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biology. 2011/09/01 2011;8(5):706-713.
53. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences. 2008;105(30):10513-10518.
54. Li A, Yu J, Kim H, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clinical cancer research : an official journal of the American
Association for Cancer Research. Jul 1 2013;19(13):3600-3610.
55. Rockacy M, Khalid A. Update on pancreatic cyst fluid analysis. Annals of gastroenterology. 2013;26(2):122-127.
56. Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Science translational medicine. Jul 20 2011;3(92):92ra66.
57. Neelakandan K, Babu P, Nair S. Emerging roles for modulation of microRNA signatures in cancer chemoprevention. Current cancer drug targets. Jul 2012;12(6):716-740.
58. Pritchard CC, Kroh E, Wood B, et al. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer prevention research (Philadelphia, Pa.). Mar 2012;5(3):492-497.
59. Chin LJ, Slack FJ. A truth serum for cancer--microRNAs have major potential as cancer biomarkers. Cell research. Oct 2008;18(10):983-984.
60. Berger F, Reiser MF. Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences? Theranostics. Nov 30 2013;3(12):943-952.
61. Ross SA, Davis CD. The emerging role of microRNAs and nutrition in modulating health and disease. Annual review of nutrition. 2014;34:305-336.
62. Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annual review of microbiology. 2010;64:123-141.
63. Grasedieck S, Sorrentino A, Langer C, et al. Circulating microRNAs in hematological diseases: principles, challenges, and perspectives. Blood. Jun 20 2013;121(25):4977- 4984.
64. Chang KH, Mestdagh P, Vandesompele J, Kerin MJ, Miller N. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC cancer. Apr 29 2010;10:173.
65. Song J, Bai Z, Han W, et al. Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Digestive diseases and sciences. Apr 2012;57(4):897-904.
66. Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. Jun 28 2007;26(30):4442-4452.
67. Nana-Sinkam SP, Croce CM. Clinical applications for microRNAs in cancer. Clinical pharmacology and therapeutics. Jan 2013;93(1):98-104.
59
68. Frampton AE, Gall TM, Giovannetti E, et al. Distinct miRNA profiles are associated with malignant transformation of pancreatic cystic tumors revealing potential biomarkers for clinical use. Expert review of molecular diagnostics. May 2013;13(4):325-329.
69. Tang RS, Weinberg B, Dawson DW, et al. Evaluation of the guidelines for management of pancreatic branch-duct intraductal papillary mucinous neoplasm. Clinical
gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Jul 2008;6(7):815-819; quiz 719.
70. Ferrone CR, Correa-Gallego C, Warshaw AL, et al. Current trends in pancreatic cystic neoplasms. Archives of surgery (Chicago, Ill. : 1960). May 2009;144(5):448-454.
71. Hutchins G, Draganov PV. Diagnostic evaluation of pancreatic cystic malignancies. The Surgical clinics of North America. Apr 2010;90(2):399-410.
72. Khalid A, Brugge W. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. The American journal of gastroenterology. Oct 2007;102(10):2339-2349.
73. Leeflang MMG. Systematic reviews and meta-analyses of diagnostic test accuracy. Clinical Microbiology and Infection. 2014/02/01/ 2014;20(2):105-113.