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Management of intraductal papillary mucinous neoplasm of pancreas (IPMN) An Update

Management of intraductal papillary mucinous neoplasm of pancreas (IPMN) An Update. KOK SIU YAN AMY United Christian Hospital. IPMN. Introduction Classification Investigation Indication for resection Methods of resection Follow-up Prognosis. Introduction. History: 1982

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Management of intraductal papillary mucinous neoplasm of pancreas (IPMN) An Update

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  1. Management of intraductal papillary mucinous neoplasm of pancreas (IPMN)An Update KOK SIU YAN AMY United Christian Hospital

  2. IPMN • Introduction • Classification • Investigation • Indication for resection • Methods of resection • Follow-up • Prognosis

  3. Introduction • History: 1982 • Described by Ohashi and his colleagues • Incidence ~2.04 per 100 000 • Autopsy studies 25% of cystic pancreatic lesions • 30-50% may become invasive • Accounts for 5-7% of all pancreatic neoplasm Dtsch Arztebl Int. 2011 Nov;108(46):788-94. Intraductal papillary mucinous neoplasia (IPMN) of the pancreas: its diagnosis, treatment, and prognosis. Grützmann R, Post S, Saeger HD, Niedergethmann

  4. Presentation DtschArztebl Int. 2011 Nov;108(46):788-94.. Intraductal papillary mucinousneoplasia (IPMN) of the pancreas: its diagnosis, treatment, and prognosis. Grützmann R, Post S, Saeger HD, Niedergethmann M.

  5. Management guideline First international consensus guideline in 2006 and was revised in 2012

  6. classification • Main duct • Branch duct • Mixed

  7. classification

  8. Investigation • USG • CT • MRI + MRCP • EUS +/- FNAC • ERCP • Intraductal USG or pancreatoscopy

  9. investigation • USG • Size and extent • CT • Diffusely distended pancreatic duct with mucinous filling defects and cystic space occupying lesions • Sensitivity 42%

  10. investigation • MRI with MRCP • Entire pancreatic parenchyma and the intra-abdominal organs • More sensitive to detect mural nodules • Sensitivity 88% Br J Surg. 2009 Jan;96(1):5-20. Preoperative tissue diagnosis for tumours of the pancreas. Hartwig W, Schneider L, Diener MK, Bergmann F, Büchler MW, Werner J.

  11. Investigation • EUS-FNA • CEA • Amylase • Cytology • Molecular analysis • Investigational • Small BD-IPMN

  12. investigation

  13. INDICATIONS FOR RESECTION • MD-IPMN • BD-IPMN

  14. 2006 guideline: MD-IPMN • Main duct dilatation≥1cm • Frequency of malignancy: 60-92% • No clinical parameters accurately discriminate malignant and non-malignant lesion RESECT ALL MAIN DUCT AND MIXED VARIANT IPMN IF SURGICALLY FIT

  15. 2006 guideline: BD-IPMN

  16. 2012 guideline

  17. 2012 guideline: BD-IPMN

  18. 2012 guideline: BD-IPMN • High-risk stigmata • Obstructive jaundice in patient with cystic lesion of the head of pancreas • Enhancing solid component within cyst • Main pancreatic duct ≥10mm in size CONSIDER SURGERY IF CLINICALLY APPROPRIATE

  19. 2012 guideline: BD-IPMN • Worrisome features • Clinical: pancreatitis • Imaging: • cyst≥3cm • Thickened/enhancing cyst walls • Main duct size 5-9mm • Non-enhancing mural nodule • Abrupt change in calibre of pancreatic duct with distal pancreatic atrophy PERFORM ENDOSCOPIC ULTRASOUND

  20. 2012 guideline: BD-IPMN • EUS features: • Definite mural nodule • Main duct features suspicious for involvement • Cytology: suspicious or positive for malignancy CONSIDER SURGERY IF CLINICALLY APPROPRIATE

  21. 2012 guideline: BD-IPMN

  22. 2012 guideline: MD-IPMN • MD-IPMN • Main duct dilatation≥5mm • 5-9mm  worrisom features • Evaluation • No immediate resection

  23. Method of pancreatectomy • According to site and extend of disease • Pancreatoduodenectomy • Distal pancreatectomy • Total pancreatectomy • Limited resection • Excision • Enucleation • Uncinatectomy • Laparoscopy +/- lymph node dissection

  24. follow-up • Non-resected IPMN • Surgically resected IPMN

  25. 2006: non resected IPMN

  26. 2006: resected IPMN • Benign: • Yearly CT/MRI • Malignant • 6 monthly CT/MRI • CEA & CA19.9 no value

  27. 2012: Non-resected IPMN

  28. 2012: Resected IPMN • Surgical margin status • normal pancreatic tissue • non-dysplastic changes • low grade dysplasia • moderate grade dysplasia • invasive carcinoma Repeat exam 2-5 years Hx/PE/MRCP half-yearly Identical to PDAC

  29. prognosis • Complete resection of noninvasive IPMN • 5 year survival rate 95% • Complete resection of early stage tumors(T1N0) • 5 year survival rate 60% • Advanced or nodal positive tumors • 5 year survival rate 36%

  30. Conclusion

  31. investigation • High-risk stigmata surgery • Smaller cyst + worrisome features EUS • Cyst >3cm + NO worrisome features EUS if elderly • Cyst ≤3cm + NO worrisome features surveillance

  32. Md-ipmn • High incidence of malignant/invasive lesions (61.6%/43.1%) • Segmental ectatic type/Diffuse type with focal lesions • Diffuse type without focal lesions • Frozen section • Intraductal USG/pancreatoscopy

  33. Bd-ipmn • Mean frequency of malignancy/invasive cancer (25.5/17.7%) • Elderly • Annual malignancy risk 2-3% • High risk factors: • Mural nodules • High grade dysplasia/Positive cytology • Rapidly increasing size • Individual decision

  34. Family history • One 1st degree relative with PDAC 2.3-fold increased risk • high-quality MRI/MRCP or CT and EUS • Malignant stigmata/worrisome features • resection • No malignant stigmata/worrisome features • MRI/MRCP or CT at 3-month intervals • EUS annually for first 2 years

  35. Distinction of BD-IPMN from mcn & other pancreatic cyst • Combination of clinical & imaging characteristics can provide preoperative diagnosis of cyst type • Multidetector CT (MDCT) & MRCP are useful for defining morphology, location, multiplicity, and communication with the MPD • Distinguishing features: multiplicity & visualisation of a connection to MPD • EUS: delineate malignant characteristics eg mural nodules & invasion but operator dependent • Cyst fluid x CEA, amylase & cytology cannot distinguish MCN & IPMN • Molecular analysis for GNAS mutations can distinguish MCN from BD-IPMN

  36. Distinction of BD-IPMN from serous cystic neoplasm (SCN) • 3 morphological patterns: • Polycystic • Honeycomb • Oligocystic Distinguished from SCN with a polycystic or honeycomb pattern by CT or MRCP Differentiation between a small oligocystic SCN & a BD-IPMN may require EUS-FNA with cyst fluid CEA determination

  37. Pancreatic cyst • Neoplastic cysts: • Non-mucinous • Serous cystic neoplasm (SCN) • Solid pseudopapillary neoplasm (SPN) • Mucinous • Mucinous cystic neoplasm (MCN) • Intraductal papillary mucinous neoplasm (IPMN)

  38. PANCREATIC CYST

  39. MCN • Low prevalence of invasive carcinoma (<15%) • Resection is recommended • Young • Risk of progression • Locations in body and tail • High cost of long-term FU • Distal pancreatectomy • Parenchymal-sparing resection (middle pancreatectomy) • Laparoscopic

  40. EUS-FNA • Apart from imaging, elevated cyst fluid CEA is a marker that distinguishes mucinous from non mucinous cysts, but NOT benign from malignant cysts • A cut off of >/=192-200ng/ml is ~80% accurate for diagnosis of mucinous cyst • Cyst fluid amylase is shown to be not uniformly elevated in IPMN • Fluid cytology may add value especially for evaluation of a small BD-IPMN without “worrisome features”. • High grade epithelial atypia recognised in cyst fluid predicted malignancy in a mucinous cyst with 72% sensitivity in one study and detected 30% more cancers in small IPMN without worrisome features in another study • Some studies showed molecular analysis of cyst fluid may be helpful in distinguishing significant mucinous cysts from indolent cysts that can be conservatively managed • However, in view of the inconclusive evidence, this guideline suggests cyst fluid analysis is still investigational, but is recommended for evaluation of small BD-IPMN without worrisome features only in centres with expertise in EUS-FNA and cytological interpretation

  41. prognosis • Synchronous/metachronous malignant diseases in extra-pancreatic organs • 20-30% • Frequency and location of extra-pancreatic malignancies differs • GI cancer is common in Asia • Skin/breast/prostatic cancers common in US

  42. conclusion • This comprehensive guideline has lowered the criterion for characterising MD-IPMN to MPD dilatation of >5mm without losing specificity for radiologic diagnosis • -high risk stigmata and worrisome features have been defined to stratify risk of malignancy in BD-IPMN and consider resection or increased freq of surveillance • -resection is recommended for all surgically fit patients with MD-IPMN or MCN • Indications for resection of BD-IPMN are more conservative • BD IPMN >3cm without high risk stigmata can be observed without immediate resection

  43. A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN.  • Am J Gastroenterol. 2013 Jun;108(6):1003-9. doi: 10.1038/ajg.2013.42. Epub 2013 Mar 5. • Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a multicentre case-control study.

  44. MR LKF 75/m • Good past health • No history of pancreatitis • No family history of pancreatic cancer • Physical examination: unremarkable

  45. Ultrasound 2.5cm cystic lesion over pancreas What should we do next?

  46. Pancreatic cyst Differential diagnosis • Benign – Pseudocyst – Serous cystic neoplasm (SCN) – Simple cyst, retention cyst, congential, lymphoepithelial cyst • Potentially malignant – Intraductal papillary mucinous neoplasm (IPMN) – Mucinous cystic neoplasm (MCN) – Solid pseudopapillary neoplasm (SPN) – Neuroendocrine tumor • Malignant – Ductal adenocarcinoma

  47. Pancreatic cyst Pathological diagnosis (n = 212) Fernandez-del Castillo et al. Arch Surg 2003

  48. introduction • WHO classification of digestive system 2010 • IPMN with low or intermediate grade dysplasia • IPMN with high grade dysplasia • IPMN with invasive cancer

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