Intraductal Papillary Mucinous Neoplasms: We Still Have a Way to Go! Francesco M. Serafini, MD, FACS

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1 Intraductal Papillary Mucinous Neoplasms: We Still Have a Way to Go! Francesco M. Serafini, MD, FACS Brooklyn VAMC September 21 st GI Grand Rounds

2 - What is it? - Clinical entity that has emerged from obscurity with increasing prevalence

3 Initially identified in % to 10% of all exocrine tumors 25% of all cystic tumors Peak incidence 6 th 7 th decade of life Male predominance Mostly in the head of the pancreas Multifocality is common

4 WHO Intraductal Papillary Mucinous Tumors 2. Mucinous Cystic Tumors Kloppel G,Solcia E, Longnecker DS. Histological typing of Exocrine Pancreas. Berlin. Springer, 1996.

5 WHO Intraductal Papillary Mucinous Neoplasm 2. Mucinous Cystic Neoplasm Longnecker DS, Adler G, Hruban RH, Kloppel G. WHO Classification of Tumors. Lyon, IARC Press, 2000

6 WHO 1996* 2000** Intraductal mucin-producing neoplasm with tall columnar mucin-containing epithelium with or without papillary projections, involving the main pancreatic duct and/or major side branches, and LACKING OVARIAN STROMA characteristic of mucinous cystic neoplasms *Kloppel G,Solcia E, Longnecker DS. Histological typing of Exocrine Pancreas. Berlin. Springer, **Longnecker DS, Adler G, Hruban RH, Kloppel G. WHO Classification of Tumors. Lyon, IARC Press, 2000

7 Most reliable way to from MCN is at pathology!!!!

8 Differences between Mucinous Neoplasms and Tanaka M et al. Pancreatology 2006;6:17-32

9 Main Duct - One or more cystic neoplastic lesions originating within and involving the main pancreatic duct and lacking an ovarian-like stromal layer

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11 Branch Duct - One or more cystic neoplastic lesions communicating BUT NOT INVOLVING the main pancreatic duct and lacking an ovarianlike stromal layer

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13 Limitations of Imaging based classification Difficulty to quantify MD involvement Microscopic involvement of MD by BD disease Clinical significance of MD involvement

14 Mixed Type - One or more cystic neoplastic lesions communicating with and extending into the main pancreatic duct and lacking an ovarianlike stromal layer

15 DIAGNOSTICS MRI/MRCP CT thin-cut ERCP EUS the most favorite test Some Institutions Historical FNA and risk stratification Pancreatoscopy Not widely available

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21 Retrospective study out of UI 214 pts with operated from 1991 to had both CT and MRCP Blinded radiologist to pathology result

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24 CT fall short of MRCP in detecting a ductal connection CT fall short of MRCP at estimating main duct involvement CT fall short of MRCP in identifying branch cysts Negative impact on diagnostic accuracy Inadequate cancer risk stratification Negative influence on surgical strategy

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31 Median values of all tumor markers were significantly different between benign and malignant The CEA and Ca 72.4 have an excellent negative predictive value to diagnose malignant versus benign, and should therefore influence the decision to operate on patients without evident risk factors (size, nodules, interval change, and symptoms)

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33 Single institution study 103 pts with 29 Adenoma 17 Dysplasia 25 CIS 32 Invasive Ca

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38 1. Asymptomatic 70%-80% 2. Abdominal pain 3. Jaundice CANCER!! 4. Weight loss 5. Anorexia

39 WHO SHOULD GET RESECTED?

40 MAIN-DUCT & MIXED-TYPE SHOULD ALL BE RESECTED IN GOOD SURGICAL CANDIDATES WITH GOOD LIFE EXPECTANCY IN TERTIARY CENTERS

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42 60% have cancer (in-situ or advanced) 30% were asymptomatic Most frequent symptom was mild abdominal pain Jaundice and diabetes are predictive of cancer 5 and 10 yrs survival no cancer was 100% 5 and 10 yrs survival with cancer was 60% and 50%

43 Malignant transformation Main Duct - Tanaka M et al. Pancreatology 2006;6:17-32

44 Asymptomatic lesions can harbor cancer No objective parameters to benign vs malignant High-degree of progression into cancer Notable in 5yrs survival benign vs malignant

45 ASYMPTOMATIC AND <3CM BRANCH-DUCT WITHOUT RISK FACTORS CAN BE SAFELY OBSERVED

46 BRANCH-DUCT WITH SYMPTOMS, >3CM, MURAL NODULES, INTERVAL CHANGE IN MRCP SHOULD BE RESECTED IN GOOD OPERATIVE CANDIDATES AT TERTIARY CENTERS

47 Malignant transformation Side Branch - Tanaka M et al. Pancreatology 2006;6:17-32

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49 ARE WE ALL READING FROM THE SAME PAGE?

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60 January 2009 June 2010

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80 Main-Duct Adenoma or low grade PanIN OK Boarder-line, HG-D or CIS or CA Resect to normal Multifocal Branch-Duct Symptomatic or radiologically bad

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82 513 pts were resected for at 2 Centers 113 (22%) had inv- Mean F/U 33 months PD 66, DP 17, TotP 17 primary ADCA vs inv-: Nodes Stage Survival

83 Histologic Type

84 WHAT ARE WE TRYING TO ACHIEVE?

85 Prevent cancer Treat early lesions Don t make things worse

86 Surgeon s operative mortality Predicted operative mortality for that patient Probability that lesion is malignant Survival between resecting and observing the lesion

87 Probability that lesion is malignant in > 15% of cases Life expectancy gained is >5 years Surgeon individual operative mortality is <8%

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89 Biomarkers to between malignant and non-malignant

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91 TIME TO CLOSE!! should be managed by expert team. Don t pock the skunk!!!!!! Don t look for glory!!!! Keep your mortality very low!! Look at your % s before you talk to patients Get it all out, but don t make things worse!

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