Pancreas Adenocarcinoma Facts

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1 IMAGING SOLID AND CYSTIC LESIONS IN PANCREAS Disclosures Received Grant Support from GE Healthcare Dushyant Sahani, M.D Director of CT Associate Professor Department of Radiology Massachusetts General Hospital Harvard Medical School Exocrine Ductal adeno Ca (80%) Rare Solid pseudopapillary Acinar cell Giant-cell Pancreaticoblastoma Solid Pancreas Lesions Endocrine Islet Cell (1-5%) Other Metastases Lymphoma Mimics Pancreatitis IP Spleen Lymph nodes Focal Fat Pancreas Adenocarcinoma Facts Fourth most common in cancer mortality (33,370 deaths in 2007 & 34,200 diagnosis*) Aggressive biology & late presentation <20% are resectable Complex regional anatomy Lack of reliable tumor markers Warshaw AL et al. NEJM 1992 *American Cancer Society 2007 data Pancreas Lesion Lesion Detection June Jan 2004 June 2004

2 MGH Management Algorithm Group 1 +METASTASES Chemotherapy SUSPECTED PANCREATIC CANCER IMAGING Group 2 NO METASTASES +Vascular encasement Chemoradiation +/- IORT Group 3 NO METASTASES No/partial encasement Surgery Fernandez-del Castillo et al. Arch Surg 1995 Technique: Pancreas MDCT/CTA Optimal scan timing for dual-phase technique Thin collimation 1-3 mm Oral contrast IV contrast Rapid injection 4-5 cc/sec Post processing Lu D et al. Radiology 1996/97. Boland G et al AJR Ichikawa T et al. AJR 2006 Lesion Detection CT: Suboptimal Technique Portal phase Arterial Optimal Technique 30 sec Venous Islet cell Arterial Pancreatic Adeno CA 45 sec Portal Venous Phase for Liver Metastases 2D/3D Display: Staging Pancreatic Duct Changes Vargas R et al. AJR 2004 Sahani D et al. Radiology 2005 Fukushima H et al. Eur Radiol 2006

3 CTA Visualization tools: Vascular Involvement CT Pancreatogram Combined IPMN Divisum IPMN in Ventral duct MRCP: Recent Advancements PD Stricture Pre-secretin 3D-MRCP Post-secretin PD obstruction- Ominous sign Aggressive approach to evaluate the site of transition Gangi et al AJR 2002 Duct Cut off : Early Detection AP PVP Criteria: Unresectable Tumor Unresectable tumor Tumor occlusing SMV/PV Reduced vessel caliber Tear drop SMV (borderline) Involvement of (> 25% lumen) CA/HA/SMA Distant metastasis (liver peritoneum) Resectable GDA/SA/SV Small veins Lymph nodes Warshaw AL et al Archives of Surgery 1990 Saldinger J. Gastrointest Surg 2000

4 Tumor (T) Staging of Pancreatic CA SMV Resectable SMV Unresectable SMV Borderline SMV Celiac Surgical mortlity 34% when arterial reconstruction undertaken and 2.7 % for venous resection Saldinger J. Gastrointest Surg 2000 Nakao A et alworld J of Surgery 2006 Stitzenberg KB et al. Ann of Surg Onc 2008 Multiphase Helical CT In Evaluating Resectability Of Pancreatic Carcinoma NPV 97.5% (unresectable) PPV 75.86% (Resectable) Sensitivity 90.67% Accuracy 90.72% Multiphase MDCT In Evaluating Resectability Of Pancreatic Carcinoma NPV 100% PPV 89% Sensitivity 100% Specificity 72% Lu D et al Radiology Keogan MT et al. Radiology 1997 Huang QJ et al Hepatobiliary Pancreat Dis Int.2002 Nov;1(4):614-9 Fletcher JG et al. Radiology Vargas R et al AJR Zamboni G et al Radiology Pancreas Neuroendocrine Tumors 1-5% of Pancreas neoplasm 10-30% in MEN-1/ 1%VHL NF-PNET >F-PNET Insulinomas > Gastrinomas> Glucaganomas NF-PNET and Insulinomas often single Tail-48%, Body-16%, Head-31% Curative resection 15 year survival 96 % 26% with liver metastases Comparison of Non-functional PNENs Study non-functional size malignancy 5yr survival Mayo Clinic 1981 n=168 15% Not available 92% 44% Johns Hopkins % 5.1cm 60% 52% n=125 MGH % 4.5cm 30% 78% n=168 Plockinger U et al. Neuroendocrinology 2004 Archives of Surgery 2007; 142: Archives of Surgery 2007; 142:

5 Functioning PNET Non-Functioning PNET Small (< 2 cm) and arterially enhancing >2 cm lesions can be heterogeous Liver metastases often arterially enhancing Large (> 3cm), exophytic, heterogenous lesions +/- cytic changes (degeneration). Vascular enacesment and metastases +/- Pfannenberg AC et al. Abd Imaging Bordianau L et al. Surgery 2008 CT Accuracy in F-PNET Detection (Tumor size & CT Technique) < 1cm - 20% 1-3 cm % > 3 cm -> 75% Extra pancreatic Sn 35% MDCT Pitfall: Small Liver Lesion Detection and Characterization MDCT 63-94% Sn Octreoscan (50% SR+) EUS 94% Sn for < 1cm lesions Wank SA. Gastroenterology 1987 Fidler J et al. AJR Gouya H et al. AJR Yong, E and Canto, M. GIE 2007;65(5) CECT Vs. MRI Holalkere et al. JCAT 2005 M-Stage: CT and MR M-Stage: Role DWI imaging CECT MR CT understages (>25% complete CT macroscopic surgery) T2 WI DWI-MR Rummney E et al. AJR Koh DM et al. Eur Radiol Bruegel M et al. Eur Radiol Laurent V et al. Eur J Radiol Post -Gd T1 FS

6 B M-stage: MR vs. FDG-PET PET Sensitivity Lesions > 2 cm=100%, 30-60% lesions < 10 mm Post-CXT 63% overall sensitivity Author M Stage: MRI-PET-CT Primary Cancer n Gold Standard Accuracy CE-MRI PET CT Rappeport et al. (18) CRC 35 Surgery IOUS 82% 77% 77% Delbeke et al. (25) CRC 52 Surgery Follow-up -- 92% 78% FDG-PET Metastases: 65 Lesions <1cm: 12 MRI Metastases: 88 Lesions <1cm 33 Kinkel. Radiology Sahani. AJR Akhurst T. JCO Coenegrachts K. Radiology Sahani et al. (28) Ward et al. (34) Regge et al. (76) CRC and Pancreatic Cancer CRC (56), Others (2) 34 Surgery Follow-up 97 % 85.3% Surgery IOUS 92% -- 82% CRC 125 Surgery IOUS % MDCT: Small Lesion Detection MRI/MRCP: Non-contour Deforming Mass CT T2 MRI T1 FS Schima W et al. AJR 2002 Schima W et al. AJR 2002 DWI MRI: Tissue Characterization Diffuse sausage-shaped enalargement of the pancreas Absence of the normal pancreatic clefts (featureless) Peripheral halo rim of hypoattenuation Lack of vascular encasement IgG4 Steroid responsive Sahani et al. Radiology 2005 Takahashi et al. AJR 2008 PDAC ADC mass 1.93±0.93 x10-3 mm 2 /s ADC normal pancreas 2.37±0.98x 10-3 mm 2 /s ADC ratio 0.8±0.07 (p 0.01) (p < 0.001) (p < 0.001) MF-AIP Catalano et al. RSNA 2009 ADC mass 1.11±0.14 x10-3 mm 2 /s ADC normal pancreas 1.03±0.22x 10-3 mm 2 /s ADC ratio 1.1±0.01

7 PET-CT: PANCREATIC CANCER PET/PET-CT: PANCREATIC CANCER Author Sensitivity Specificity Accuracy Zimmy (1997) Debelke (1999) Martin (2000) Benefits of State of art MDCT and PET Morphology + Function = PET-CT Heinrich (2005) 93 Heinrich S et al. Ann Surg 2005 ROLE OF PET/CT- CHARACTERIZATION LYMPH NODE (N) STAGING PET-CT CT FDG-PET Tumor PET/CT: PANCREATIC CANCER STAGING FDG-PET-CT: PNET Management changed in 16%, initially considered resectable Additional distant metastasis in 5 patients Synchronous rectal cancer in 2 patients. Heinrich S et al. Ann Surg 2005;242: PET-CT attractive but its role is unclear Differentiation between benign and malignant lesions is difficult

8 Summary PD dilatation with a cut-off ominous sign MDCT first line modality For pancreas mass evaluation Pre-operative staging Optimal scanning technique and 2D/3D display For lesion detection and staging MRI for liver evaluation and problem solving indications (small lesion detection) PET-CT attractive but its role is still evolving Summary Functional imaging is complimentary to cross sectional imaging for F-NET location Assessment of prognosis and response to therapy PET-CT attractive but its role is unclear Differentiation between benign and malignant lesions is difficult EUS has the best performance for small lesion detection Pancreas Surgery At MGH Cystic Tumor Distribution Serous cystadenoma: 32-39% Mucinous neoplasm: 10-45% increase in cystic tumors from 16-30% Fernandez-del Castillo C. Adv Surg 2000 IPMN: 21-33% Cystic Degeneration in Solid Tumors Cystic Lesion: Imaging Objectives Morphologic details Unilocular or Multilocular < 10% Microcystic Cyst communication with PD Neuroendocrine Solid and Pseudopaillary Neoplasm (SPEN) Adenocarcinoma Extent of PD involvement Megibow A Radiology 1992, Procacci C JCAT 1999/2000. Sahani DV ECNA 2005/Radiograhics 2005/JACR 2009

9 Cystic Lesion: Imaging Objectives Benign or Malignant Mural nodules Thick Septae Cyst/MPD size Metastases SEROUS CYSTADENOMA: MICROCYSTIC Middle age Women >Men Numerous (> 6) tiny cysts Sponge / Honeycomb Lobulated outline Sharp interface with vessels Rarely obstruction Bile duct Pancreatic duct Buck et al. Radiograhics 1990 SEROUSCYSTADENOMA Sponge Honeycomb MUCINOUS CYSTIC NEOPLASM (MCN) Middle age women Tail location (85%) most common Single/few cysts ( < 6 cyst) > 2cm Peripheral/septal Ca+/mural nodules No communication with PD Benign or malignant 10-20% are carcinoma MUCINOUS CYSTIC NEOPLASM CT INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS (IPMN) Increasingly recognized Similar to MCNs cystic tumor that secrete mucin Arise from a duct papillary epithelium Affect a mostly elderly men. Dilatation of the ducts as a result of tumor growth and mucin Upto 49% of IPMNs may be malignant Ohhashi K et al Prog Dig Endosc 1982;20:

10 IMAGING FEATURES:SB-IPMN IPMN Classification Uncinate >other Septated cyst -lobulated Channel of communication -MPD 96% specific for diagnosis +/- MPD dilatation > 5mm % risk of malignancy Invasive Ca less common MCN Macrocystic <6 cysts, > 2 cm in size Surface-Smooth 85%Tail SB-IPMN Vs MCN MAIN DUCT IPMN Tumor foci ERCP SB-IPMN Macrocystic or mixed >6 cysts of < 2cm Communication Lobulatated +/-MPD dilatation SB IPMN Irie et al Radiology 2002 Fukukura,Y Acta Radiol 2003, Sahani et al Radiology 2005 Segmental or diffuse dilated MPD > 6 mm without cut-off Irie H et al. AJR 2000; 174: MRCP MD-IPMN:FEATURES MPD++/ SB-changes Atrophy =MPD dilatation Bulging papilla Mural nodules IPMN PD Dilatation: Differential C-Pancreatitis Pancreatic Duct Changes PDAC Irie et al Radiology 2002, Fukukura Y Acta Radiol 2003, Sahani et al Radiology 2005 Vargas R et al. AJR 2004 Sahani D et al. Radiology 2005 Fukushima H et al. Eur Radiol 2006

11 CYST CLASSIFICATION-NON MUCINOUS SOLID PSEUDOPAPILLARY TUMOR Solid + cystic Irregular enhancing peripheral component Capsule, Ca+ rim Young women (20-30 yrs) SOLID MASS WITH CYSTIC DEGENRATION Associated changes in duct, parenchyma, vascular or ductal invasion or LN unilocular multilocular Pancreas Cyst Review CYST PSEUDOCYST IPMN MUC CYSTADENOMA complex SER CYSTADENOMA MUC CYSTADENOMA Complex solid + cystic No characteristic features NET/Adenoca/Met MUC CYSTADENOCARCINOMA MALIG IPMN Challenges in Cyst Characterization: Morphologic Overlap SCA Morphology Challenges Macrocystic Central scar: < 20% Mucinous Pseudocyst IPMN Cohen-Scali F et al. Radiolgy 2003 Khurana B et al. AJR 2003 Kim S et al. AJR 2006? Solid MRI Diffuse Cysts Features: Predictors of Malignancy MPD>8 mm WHAT IS THE ROLE OF EUS? Mural nodularity / solid mass Peripheral Calcification Macrocyst > 5cm Cyst fluid aspiration Amylase Tumor markers CEA, CA 72-4, CA 125, CA 19-9, CA 15-3 Biopsy suspicious areas Less risk of spillage of cyst contents Hollerbach: Endoscopy 2001 Oct;33(10):824-31

12 MDCT CATEGORIZATION: CYST MORPHOLOGY Cyst Fluid Analysis (CEA,amylase,cytology) Morphology CEA<5 CEA CEA >500 Serous cyst Duplication Mucinous Pseudocyst Mucinous Malignant Microcystic Cyst with associated mass Non-mucinous cytology Mucinous or inflammatory cytology Mucinous cytology Benign or malignant Brugge W et al. AGA 2002 Septated/Macrocystic Unilocular Sahani et al. Radiograhics 2005 ALGORITHM FOR MANAGEMENT OF PATIENTS WITH A PANCREATIC CYSTIC LESION MANAGEMENT ALGORITHM CT scanning Abdominal CT scan Premalignant or malignant Macrocystic Malignant Inflammatory Cyst/pancreatitis Microcystic Macrocystic Malignant high EUS-FNA Risk / Benefit Assessment low Surgery Management depends on* Age & presentation, location of the lesion and size presence or absence of malignancy Gigiot JF et al Arch Surg 2001;136: * Surgery CEA>500 Atypia Cytology and CEA Monitoring CEA Benign mucinous CEA<10 Non-mucinous Observation CHALLENGES WITH SMALL CYSTS (< 3 CM). Accurate diagnosis difficult with imaging. Most benign side branch IPMN MRCP better for small cyst morphology Criteria for F/U No solid component No MPD involvement Clinical CT MR Spinelli 2004 Fernandez del-castillo 2004 Sohn 2004 Sahani 2006 Cyst Follow-up May 2006 August 2007 Nov 2001 June 2003 August 2004 Sept 2005 Worrisome 1cm growth/year Solid mass PD

13 APPROACH ON IMAGING MORPHOLOGIAL DETAILS Summary MDCT/MR has good predictive value for malignancy, better for benignity Pseudocyst Epithelial cyst Serous MCN Peripheral Mucinous IPMN Ductal Cystic deg. in solid tumors Differentiation of borderline and CIS changes (prevalent in mucinous lesions) is difficult on imaging Called Malignant Triaging Patients MDCT features Clinical presentation Age Surgical risk Lesion size / location Called Benign Small, C IPMN Sahani, D. V. et al. Radiographics 2005;25: Summary Incidental < 3 cm cysts (-solid component) have low incidence of malignancy MR>CT for cyst morphology FU with CT or MR 6 months EUS and cyst aspiration useful but should considered in select patients. THANK YOU Bulfinch Building, Massachusetts General Hospital