Il ruolo dell'ecoendoscopia nella diagnosi delle lesioni solide pancreatiche - Gastrolearning®

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Published on March 3, 2014

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Gastrolearning II modulo/4a lezione
Il ruolo dell'ecoendoscopia nella diagnosi delle lesioni solide pancreatiche
Prof. A. Larghi - Università Cattolica Sacro Cuore (Roma).

Il Ruolo dell’Ecoendoscopia nelle Lesioni Pancreatiche Alberto Larghi MD, PhD Digestive Endoscopy Unit European Endoscopy Training Centre Catholic University, Rome

Endoscopic Ultrasound Historical Background 1970 1980 Development of the technique First studies published in the literature Hisanaga K. AJR 1980; Di Magno EP. Lancet 1980; Strohm WD. Endoscopy 1980 1984-88 Diagnostic EUS: Staging of luminal GI and pancreatic cancers Caletti GC. Scand J Gastroenterol 1984; Tanada Y. Scand J Gastroenterol 1984; Yasuda K. Gastrointest Endosc 1988. 1992 EUS-FNA Vilman P. Gastrointest Endosc 1992; Wegener M. Ultraschall Med 1992 1996 Interventional EUS Wiersema MJ. Gastrointestinal Endoscopy 1996; Gress F. Gastrointestinal Endoscopy 1996; Giovannini M. Endoscopy 2001 2013 Therapeutic EUS

Radial Echoendoscope Radial EUS Ultrasound beam

Linear Echoendoscope Linear EUS Mass Ultrasound beam

Pancreatic Lesions Role of EUS  Screening  Equivocal results of previous imaging modalities  Differential diagnosis and risk assessment  Staging  Therapy/Interventional EUS

High-Risks Individuals* Risk Group Gene Life Time Risk* PRSS1 40% STK 11/LKB1 36% Familial Atypical Multiple Mole Melanoma (FAMMM) CDKN2a 17% Familial Breast-Ovarian Cancer (FBOC) with one affected FDR BRCA2 10%-15% Familial Pancreatic Cancer unknown Hereditary Pancreatitis Peutz-Jeghers Syndrome PC in ≥ 3 blood relatives (at least 1 FDR) PC in ≥ 2 FDR PC in ≥ 2 blood relatives (at least 1 FDR) *>5% lifetime risk, or fivefold increased RR 40 8%-12% 6% Canto MI. GUT 2013;62:339-47.

High-Risks Individuals How to Screen MRCP/EUS When to Start 40 yrs for HP/ 50 yrs for others How frequently to Surveil Yearly

High-Risks Individuals Results of Screening Canto MI. GUT 2013;62:339-47.

Pancreatic Lesions Role of EUS  Screening  Equivocal results of previous imaging modalities  Differential diagnosis and risk assessment  Staging  Therapy/Interventional EUS

Detection of Pancreatic Cancer EUS vs. CT Non specific CT changes (enlarged, prominent pancreas) No. Of Patients Rate of malignancy Ho, 2006 50 8% Singh, 2008 107 21% Horwhat, 2009 69 9% Reddymasu, 2011 320 9% Author, yr

Detection of Pancreatic Cancer EUS vs. CT 104 patients with suspected pancreatic cancer  80 with confirmed PC  Sensitivity 98% vs. 86%, P=0.012  for masses ≤25mm, 89% vs. 53%, P=0.07 DeWitt J. Ann Intern Med 2004;141:753-63. Non specific CT changes (enlarged, prominent pancreas) All Lesions° EUS 93 MDHCT* 74 Insulinoma^ 84 32 *64-slice CT; °P=0.06; ^P=0.001 Khashab MA. Gastrointest Endosc 2011;73:691-6.

Detection of Pancreatic Cancer EUS Performance HIGH NEGATIVE PREDICTIVE VALUE Pts. negative EUS Negative Predictive Value Mean f/u Catanzaro, ‘03 58 100% 24 Klapman, ‘05 155 100% 25 Author (mos.) Catanzaro Al. Gastrointest Endosc 2003;58:836-40. Klapman JB. Am J Gastroenterol 2005;100:2658-61.

Pancreatic Lesions Role of EUS  Screening  Equivocal results of previous imaging modalities  Differential diagnosis and risk assessment  Staging  Therapy/Interventional EUS

EUS-FNA Unresectable Tumors EUS-FNA when available is the procedure of choice for obtaining a pathologic diagnosis to start chemoRT

Unresectable Tumors EUS-FNA vs CT/US-FNA Restrospective study on 1050 pancreatic FNAs:  EUS (843), US/CT (207)  For lesions ≤ 3cm, EUS accuracy significantly better than CT/US (p=0.015) Volmar KE. Gastrointest Endosc 2005;61854-61. Prospective randomized study on 84 pancreatic FNAs:  EUS (41), US/CT (43)  EUS vs. US/CT: sensitivity 84% vs. 62%, p=ns accuracy 89% vs. 72%, p=0.074 Horwhat JD. Gastrointest Endosc 2006;63:966-75. Eloubedi M. Gastrointest Endosc 2006;63:622-9.

Seeding EUS-FNA vs. US/CT-FNA Incidence of peritoneal carcinomatosis   EUS-FNA Percutaneous FNA 2.2% 16.3% P < 0.025 Micames C. Gastrointest Endosc 2003;58:690-5. American Joint Committee on Cancer EUS-FNA preferred sampling technique for pancreatic cancer

EUS-FNA for Pancreatic Masses Performance Meta-analysis and systematic review (41 studies; 4766 patients)  Pooled sensitivity 86.8% (95% CI, 85.5-87.9)  Pooled specificity 95.8% (95% CI, 94.6-96.7)  Positive likelihood ratio 15.2 (95% CI, 8.5-27.3)  Negative likelihood ratio 0.17 (95% CI, 0.13-0.21) Puli SR. Pancreas 2013;42:20-6.

Resectable Tumors Should FNA be performed? Probability of cancer-related deaths (<12 mos) after surgical resection  Patient demands definitive diagnosis  To exclude other diagnoses  Preoperative neoadjuvant Volmar KE, et al. Gastrointest Endosc 2005;61854-61. Barugola G, et al. Ann Surg Oncol 2009;16:3316:22.

EUS for Pancreatic Masses Tissue is the issue 19G 22G 25G

EUS for Pancreatic Masses Tissue is the issue Prospective study in 61 consecutive patients with pancreatic solid masses  One needle pass performed  Core biopsy samples in 55/61 (90.1%)  Sensitivity: 87.5%  Specificity: 100%  PPV: 100%  NPV: 41.7%  Diagnostic accuracy: 88.5% Larghi A. Surg Endosc 2013; 27:3733-8.

EUS-guided Needle Biopsy Interobserver Agreement for Grading  42 patients with ADK with pro-op EUS-NB and surgical specimen  4 pathologists (Rome, Marseille, Santiago di Compostela) independently reviewed biopsy slides  Overall agreement among the four pathologists was only fair (k=0.27; 95% CI: 0.14-0.38)  Agreement well-/moderately differentiated versus poorly differentiated was only fair (k=0.27; 95% CI: 0.21-0.49) Larghi A. Am J Gastroenterol 2014;submitted.

3, 2, 2, 3 1, 2, 2, 1 3, 1, 2, 2 2, 1, 3, 2

EUS-FNTA Pancreatic Neuroendocrine Neoplasms No.pts 30 Mean Age 55.7±14.9 Lesion size 16.9±6.1mm Location Uncinate Head Isthmus Body/Tail 3 5 4 18 Larghi A, et al. Gastrointest Endosc 2012;76:570-7.

EUS-FNTA Pancreatic Neuroendocrine Neoplasms  EUS-FNTA successful in all patients without complications  Adequate samples for histological examination were retrieved in 28/30 patients (92.9%) and in all of them a diagnosis of PNENs was made  Ki-67 determination could be carried out in 26/28 patients (86.6% of the initial entire cohort, and in 92.9% of the patients with successful EUSFNTA) Larghi A, et al. Gastrointest Endosc 2012;76:570-7.

EUS-FNTA Pancreatic Neuroendocrine Neoplasms EUS-FNTA and surgical pathology agreement in 12 pts EUS-FNTA Surgery ≤5% ≤2% 5-20% >20% 2-20% ≤ 5% 2% 8 7 1 5-20% 2-20% 1 3 2 >20% 1 Histological Grading concordance in 10/12 12/12 Larghi A, et al. Gastrointest Endosc 2012;76:570-7.

Tissue is the Issue  Tissue samples may be of additional value to perform tissue profiling that in the future will be very important to guide individualized therapies  Chemo-sensitivity and Pancreatic Cancer: can the EUS FNA replace surgical biopsy on chemo sensitivity assessment?

Pancreatic Cancer Stem Cells Isolation and Culture  48 hours from 12 days from isolation  Magnification 10X

Pancreatic Lesions Role of EUS  Screening  Equivocal results of previous imaging modalities  Differential diagnosis and risk assessment  Staging  Therapy/Interventional EUS

Pancreatic Cancer T stage T staging: T1: Tumor limited to pancreas Size ≤ 2cm in greatest dimension T2: Tumor limited to pancreas Size > 2cm in greatest dimension T3: Tumor infiltration of bile duct, papilla, duodenum and PV, SMV T4: Tumor infiltration of stomach, spleen colon, major arteries, and PV, SMV

EUS Staging Vascular Invasion Diagnostic accuracy of EUS for vascular invasion: a meta-analysis (29 studies)  Sensitivity 73%, Specificity 90%  Positive likelihood ratio 9.1 (measure of how well the test identifies the disease)  Negative likelihood ratio 0.3 (how well the test performs in excluding the disease) EUS is a better test to identify vascular invasion rather then excluding it Puri SR. Gastrointest Endosc 2007;65:788-97.

Pancreatic Cancer Vascular Invasion Sensitivity: SpecificityLiver 50-90% Confluence with PV 90-100% Stomach PV/confluence: EUS superior SMV: Mass Equivalent (~CT) Celiac trunk: Encasement of SMV Equivalent (~CT) HA, SMA: CT superior SMV

EUS-FNA in Pancreatic Cancer Staging

Pancreatic Cancer Clinical Impact of EUS-FNA  Lack of data, besides tissue diagnosis  99 patients elegible for surgery  In 12 patients (12%) EUS FNA revealed  Metastatic distant lymph nodes (6)  Liver mets (4)  Malignant ascites (1)  Retroperitoneal infiltration (1) Mortensen MB. Endoscopy 2001;33:478-83.

Pancreatic Lesions Role of EUS  Screening  Equivocal results of previous imaging modalities  Differential diagnosis and risk assessment  Staging  Therapy/Interventional EUS

Biliary Access and Drainage  Candidates:  Patients with benign and malignant biliary diseases after ERCP failure  Approach  Transgastric or transduodenal  Procedure  Rendez-vous  Direct stent placement

EUS-Guided Biliary Drainage Intrahepatic Intrahepatic Extrahepatic Extrahepatic

EUS-Guided Biliary Drainage Author, yr Maranki, 2009 Park do, 2011 Shah, 2012 Iwashita, 2012 Dhir, 2012 Vila, 2012 Horaguchi, 2012 Park do, 2013 Dhir, 2013 Khashab, 2013 Dhir, 2013 Kawakubo, 2013 Gupta, 2014 No. of Patients Technical success Clinical Success Complications 49 57 68 40 58 106 21 45 35 35 68 64 240 84% 96% 85% 73% 98% 70% 100% 91% 97% 94% 97% 95% 99% 80% 89% 85% 73% 98% 70% 100% 87% 97% 91% 97% 95% 87% 18% 47% 9% 12% 3% 23% 10% 11% 23% 14% 21% 42% 35%

Lumen-Apposing Devices Axios stent Hot Axios stent

EUS-guided Treatment of Locally Advanced Pancreatic Adenocarcinoma  EUS-guided fine needle injection (EUS-FNI)  EUS-guided Implantation Therapy  EUS-guided Tumor Ablation

EUS-guided Fine Needle Injection  Cytoimplant (allogenic mixed lymphocyte culture) for      pancreatic cancer ONYX-015 for pancreatic cancer in association with RT + Gemcitabine TNFerade in pancreatic cancer + RT TNFerade in esophageal cancer + RT+ 5FU-CDDP Immature denditric cells against pancreatic cancer OncoVEX : GM-CSF carried by Oncolytic herpes Virus

Fine Needle Injection TNFerade TNFerade in pancreatic adenocarcinoma Enhanced Tumor Necrosis IONIZING RADIATION TNF alpha Enhanced Radiosensitivity

EUS-guided FNI of Pancreatic ADK TNFerade Injection  50 pts. locally advanced panc adenocarcinoma  5 wks treatment of weekly TNFerade (4x109, 4x1010, 4x1011 particles unit in 2ml)  IV 5-FU (200mg/m2/d x 5d/wk)+Radiation (50.4 Gy)  Toxicity: mild, well tolerated  Higher dose vs. Lower doses  Greater locoregional control  Longer progression free survival  Improved median survival  4/5 pts. tumor resected with negative margins and 3 survived more than 24 mos Hecht JR. Gastrointest Endosc 2012;75:332-8.

EUS-guided FNI of Pancreatic ADK TNFerade Injection  304 pts. locally advanced panc adenocarcinoma  Randomly assigned 2:1 to standard of care plus TNFerade (SOC

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