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The Rants and Tirades of a Maniacal Senior Surgery Resident

The Rants and Tirades of a Maniacal Senior Surgery Resident. Sushanth Reddy, M.D. General Surgery Resident University of Kentucky. Last year…. Pancreatic Cystic Lesions. All Right, No Basic Science…. Reddy S, Wolfgang CL. Surg Clin North Am, 2007. What’s an IPMN?!!.

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The Rants and Tirades of a Maniacal Senior Surgery Resident

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  1. The Rants and Tirades of a Maniacal Senior Surgery Resident Sushanth Reddy, M.D. General Surgery Resident University of Kentucky

  2. Last year….

  3. Pancreatic Cystic Lesions All Right, No Basic Science…. Reddy S, Wolfgang CL. Surg Clin North Am, 2007

  4. What’s an IPMN?!!

  5. Intraductal Papillary Mucinous Neoplasms • 1980: Japanese report 4 patients with pancreatic cancer • All had dilated pancreatic duct, mucinous features, patulous ampulla • All 4 survived at least 3 years • Over next decade: mucinous ductal ectasia, mucinous pancreatic tumor, mucin producing carcinoma of the pancreas, intraductal papillary hyperplasia, intraductal papillary neoplasm, and intraductal mucin producing tumor

  6. Intraductal Papillary Mucinous Neoplasms • 1997: MGH suggested the term Intraductal Papillary Mucinous Neoplasms (IPMN) More Intervention More Observation IPMN Pseudocysts Serous Cystic Neoplasms MCN

  7. PubMed Search Term “intraductal papillary mucinous neoplasms pancreas” accessed 1/6/10

  8. Why Are IPMN Important? • IPMN have malignant potential • There are ABSITE questions about them • They can degenerate into cancer • WHO Classification • Low Grade Dysplasia • Moderate Grade Dysplasia • High Grade Dysplasia • Invasive Cancer • All IPMN have dysplasia!!

  9. IPMN with Cancer • Pancreatic adenocarcinoma is associated with poor survival • Margin negative, node negative 5 year survival 15-20% • Lance Armstrong Foundation: “We don’t fund non-curable diseases”

  10. Poultsides GA, Reddy S, et al.Ann Surg in press

  11. IPMN - Associated vs. Standard Pancreatic AdenocarcinomaPathologic Characteristics Poultsides GA, Reddy S, et al.Ann Surg in press

  12. IPMN - Associated Invasive AdenocarcinomaHistologic Subtypes Pancreatobiliary type IPMN (Aggressive Pathway) Tubular Adeno-carcinoma Intestinal type IPMN (Indolent Pathway) Colloid Carcinoma Adsay NV, et al. Am J Surg Pathol. 2004 Jul;28(7):839-48

  13. IPMN - Associated Invasive AdenocarcinomaPathologic Characteristics Poultsides GA, Reddy S, et al.Ann Surg in press

  14. Poultsides GA, Reddy S, et al.Ann Surg in press

  15. IPMN Related Cancers • Given the favorable prognosis associated with IPMN associated cancers, an aggressive approach toward resection should be advocated • Is the favorable outcome due to an inherent biologic difference or from an earlier presentation from the same cancer?

  16. Selection for Resection • Which patients with IPMN should be resected? • Lesions with cancer • How do we know?? • High Grade Dysplasia? • Theoretically the last step until invasive cancer • Moderate or Low Grade Dysplasia? YES

  17. Progression to Cancer Sohn TA, Yeo CJ, et al. Ann Surg 2004

  18. Progression to Cancer • Large autopsy series show that PanINs are present in 18-29% of non-cancerous pancreata

  19. Selection for Resection • Should HGD, MGD, or LGD be removed? • Pancreatic resection is associated with high morbidity and mortality • Most authors report presence of invasive cancer or malignancy in IPMN • Malignancy = invasive cancer + HGD

  20. Selection for Resection • Consensus guidelines for management of IPMN • 11th Congress of International Association of Pancreatology (IAP) –Sendai Criteria • Resection indicated for: • all main duct and combined type IPMN • branch duct IPMN if: • size > 30 mm • mural nodule • Symptomatic Tanaka M et al. Pancreatology 2006

  21. Selection for Resection • International consensus guidelines based on retrospective review of 8 studies of resected IPMN – 475 patients (median 52 patients/study) • Controversy over how to manage branch duct lesions • Is it safe to follow small (< 3 cm), asymptomatic branch duct IPMN without a solid component?

  22. Branch Duct Lesions • Recommendations for branch duct IPMN based on 2 studies • 16 patients with BD-IPMN: None had invasive cancer in lesions < 3 cm • 32 patients with BD-IPMN: 12/17 BD-IPMN > 3 cm had invasive cancer • The paper did not clarify if these lesions were asssociated with solid components or symptoms • A multivariate analysis was performed and size was predictive (OR 31.15, p = 0.009)

  23. Branch Duct Lesions • Appear to behave differently than MD- or combined type IPMN • Lower incidence of malignancy and invasive cancer • Pancreatic resection associated with significant morbidity • Management guided by two studies with 33 patients between them!!

  24. Malignancy in IPMN of the Pancreas • Main duct: diffuse or segmental dilatation of the main pancreatic duct (MPD) > 5 mm without associated cystic lesion Schmidt CM et al. Ann Surg 2007 Kawamoto S, Fishman EK et al. AJR 2006

  25. Malignancy in IPMN of the Pancreas • Branch duct: dominant cystic lesion without MPD dilatation Schmidt CM et al. Ann Surg 2007 Kawamoto S, Fishman EK et al. AJR 2006

  26. Malignancy in IPMN of the Pancreas • Combined: cystic lesion with MPD dilatation > 5 mm Schmidt CM et al. Ann Surg 2007 Kawamoto S, Fishman EK et al. AJR 2006

  27. Malignancy in IPMN of the Pancreas

  28. Malignancy in IPMN of the Pancreas

  29. Malignancy in IPMN of the Pancreas Multivariate Analysis Preoperative Predictors of Invasive Cancer in Branch Duct IPMN

  30. Malignancy in IPMN of the Pancreas Solid Component and Branch Duct Lesions

  31. Malignancy in IPMN of the Pancreas • Branch-duct IPMN without solid component (n = 68): • All without invasive carcinoma • Incidence of high grade dysplasia (25%) did not correlate with: • size > 3 cm (p = 0.15) • presence of symptoms (p = 0.59)

  32. Malignancy in IPMN of the Pancreas

  33. Malignancy in IPMN of the Pancreas • Prospective, single-arm, observational study • 82 patients with branch duct IPMN • no mural nodules • asymptomatic • median lesion size 2.0 cm (range, 1.1 – 4.5 cm) • 12% of patients with lesions > 3 cm • Median follow-up 61 months • 13 patients had radiologic progression • 9 tumors enlarged • 4 developed mural nodules • 7 of 13 patients underwent surgical resection • None had invasive cancer and one had high grade dysplasia Tanno S et al. Gut 2008

  34. Summary Invasive cancers associated with IPMN have favorable survival compared to standard pancreatic adenocarcinomas Survival benefit may be due to earlier presentation of the same lesion or a biologically different entity Main duct and combined type IPMN are more likely to have an invasive cancer than branch duct IPMN Presence of a solid component strongly correlated with invasive cancer in branch duct lesions Branch duct IPMN without a solid component did not have invasive cancer but did have high grade dysplasia

  35. Summary In accordance with the IAP guidelines, main duct and combined type IPMN or branch duct IPMN with solid component have a strong association with malignancy and warrant surgical resection. Branch duct IPMN without a solid component did not harbor invasive carcinoma regardless of size. Similarly, size did not predict the presence of high grade dysplasia. Size > 3cm alone should be re-evaluated as an absolute indication for resection of branch duct IPMN without a solid component. Presence of a solid component is the strongest predictor of invasive cancer in branch-duct IPMN.

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