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Differential Diagnosis of Neoplastic Pancreatic Cysts: The Role of EUS with Guided FNA

Differential Diagnosis of Neoplastic Pancreatic Cysts: The Role of EUS with Guided FNA. Erwin M. Santo, MD. Head, Invasive Endoscopy Unit Dep. of Gastroenterology & Hepatology Tel-Aviv Sourasky Medical Center. Introduction. Cystic lesions constitute about 10 % of pancreatic tumors

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Differential Diagnosis of Neoplastic Pancreatic Cysts: The Role of EUS with Guided FNA

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  1. Differential Diagnosis of Neoplastic Pancreatic Cysts:The Role of EUS with Guided FNA Erwin M. Santo, MD Head, Invasive Endoscopy Unit Dep. of Gastroenterology & Hepatology Tel-Aviv Sourasky Medical Center

  2. Introduction • Cystic lesions constitute about 10 % of pancreatic tumors • Significant increase in detection due to widespread use of US,CT • Most lesions discovered incidentally

  3. Clinical Presentation • Asymptomatic • Abdominal pain • Jaundice • Pancreatitis

  4. Clinical Presentation Asymptomatic • Ca in situ / invasive cancer – 17% • Lesion with malignant potential – 42% Fernandez Del Castillo et al. Arch Surg 2003

  5. Classification • Non neoplastic (pseudocysts) • Neoplastic Non Mucinous Mucinous

  6. Classification Non Mucinous Cysts • Serous cystadenoma • Cystic endocrine tumors • Other

  7. Classification Mucinous Cysts • Mucinous cystadenoma • Malignant mucinous cystic tumors • Intraductal papillary mucinous neoplasms - IPMN

  8. Diagnosis • CT – microcystic appearance, central fibrosis- Serous Unilocular, macrocystic, peripheral calcification- Mucinous • MRCP – MPD dilatation, mural nodules ductal connection - IPMN

  9. Diagnosis • EUS - highly sensitive • FNA – fluid characteristics, tumor markers, cytology • CEA in fluid - most accurate marker

  10. EUS – Serous cyst

  11. EUS – Mucinous cyst

  12. Diagnosis of Pancreatic Cystic Neoplasms: A report of the Cooperative Cyst Study Brugge WR, M.D. and Colleagues Gastroenterology 2004; 126:1330-1336

  13. Optimal Cutoff CEAMucinous vs non-mucinous

  14. Differentiating between mucinous and non-mucinous lesions *p<.001 vs Cytology, EUS

  15. Combination Testing *p<.05 vs EUS morphology -cytology, EUS morphology-cytology-CEA

  16. Summary of Findings • EUS-FNA is safe for evaluation of pancreatic masses and cystadenomas • Cytology results are much better in solid lesions EUS-FNA should be used to assist in the selection of patients with a pancreatic lesion for surgical resection. Cyst fluid CEA levels should be used in conjunction with cytology for pancreatic cystadenomas

  17. AIM • Evaluation of the various parameters (clinical,morphological,fluid content, cytology) and their contribution to the ability to distinguish between serous and mucinous cystic tumors

  18. AIM • Validation of the current criteria used to distinguish between various cystic tumors (gold standard based on surgical pathology ) • Establishing new criteria with higher sensitivity and specificity

  19. AIM • Provide an algorithm for the diagnosis and treatment of pancreatic cystic lesions

  20. Heuristics used in our Institute for Dx of Serous cysts • Clinical • Microcystic morphology • CEA level < 5 ng / ml • Histology- cuboidal, non secreting cells

  21. Heuristics used in our Institute for Dx of Mucinous cysts • Clinical • Morphology – unilocular, thick septa, solid component • High viscosity (mucinous) fluid • CEA - >140 ng/ml • Histology – columnar secreting epithelium

  22. Methods

  23. Methods • Retrospective study • 170 patients between 1977-2006 • 155 patients ,195 EUS exams • 40 patients – EUSx2 or more • 101 women, 54 men • Mean age – 64.3±14 years

  24. Methods • Demographic data • Clinical presentation • Imaging – US, CT , EUS • FNA • Surgical findings • Follow up on all patients (office visits , data from family physicians, gastroenterologists, patient’s families)

  25. Methods EUS • Cyst location, size, morphology • FNA – fluid: - characteristics - cytology - tumor markers –CEA,CA19-9,CA72-4,MCA • Cyst wall sampling (cell block)

  26. Results

  27. Results

  28. Results

  29. Results • 37 patients had surgery with histological findings. • 140 patients had FNA but results were available for 80 patients.

  30. Results

  31. Results

  32. EUS-FNA vs. Surgical biopsy • 32 patients had both FNA and surgical biopsy. • The agreement rate was 66% of the cases regarding mucinous vs. non-mucinous with kappa=0.33. • Sensitivity and specificity of FNA are 59% and 80% respectively.

  33. Results • Mean of Ln(CEA)* levels were 2.6 and 5.8 for non mucinous and mucinous cases respectively (p<0.0001) • No statistically significant difference with all the other tumor markers tested • Rate of solid component in cyst – the difference was not statistically significant (p=0.14) • No difference concerning cyst size or morphology *CEA is highly skewed distributed and therefore we transformed the CEA level to Ln(CEA)

  34. BoxPlot Ln(CEA) Non-mucinous Mucinous

  35. Logistic regression results Note that CA-19 is highly correlated with CEA, and when CEA levels are unavailable the CA-19 level should play a role in the diagnostic process.

  36. Logistic regression results For example, a patient with CEA value of 10 and probability for mucinous cyst of 40% compared to a patient with CEA level of 100 the probability of mucinous cyst is 86%.

  37. ROC of CEA classification of Mucinous vs. Serous A Threshold of CEA=58 ng/ml yields 86.4% and 87.5% sensitivity and specificity respectively sensitivity 1-specificity AUC=0.902 (CI=(0.79-1.0))

  38. Conclusions • EUS is a useful tool but it can not alone distinguish between cystic lesions with variable malignant potential • EUS-FNA alone is also limited in its ability to correctly diagnose a cystic lesion – sensitivity 59% specificity 80% • Combination of parameters – cytology and CEA levels (or CA 19-9 levels) can significantly increase the diagnostic yield

  39. A Practical Decision Algorithm based on the Threshold Decision Model Source: NEJM 1980; 302:1109-17

  40. For a patient with a pancreatic cyst there are several management options: • Wait and watch approach with a follow up. • An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection. • Surgical resection of all cysts without prior EUS evaluation.

  41. Beside the preferences of the patient, the following parameters are relevant to the decision process: • Age of the patient •  60 year • 61-75 year • > 75 year • Co-morbidity status (CV diseases, diabetes, other neoplasm diseases) • No co-morbidity • Co-morbidity • Test results (CT, EUS)

  42. Natural history of mucinous cystic neoplasm 78 years old woman with incidental finding - 1977

  43. Age <=60 60 - 75 >75 No Yes Yes Co-morbidity No Positive Cytology or CEA>60 Yes No Yes No Yes No Yes No 5< CEA<60 Complexity of Surgical resection Yes No Compliance Yes No = Wait and Watch = Surgical Resection = Debate

  44. Age <=60 60 - 75 >75 No Yes Yes No Co-morbidity Positive Cytology or CEA>60 Yes No Yes No Complexity of Surgical resection = Wait and Watch = Surgical Resection = Debate

  45. Age <=60 60 - 75 >75 No Yes Co-morbidity Positive Cytology or CEA>60 Yes No Yes No = Wait and Watch = Surgical Resection = Debate

  46. Thank You

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