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

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Il ruolo dell'ecoendoscopia nella diagnosi delle lesioni solide pancreatiche
Prof. A. Larghi - Università Cattolica Sacro Cuore (Roma).

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  • Another important Indication for interventional EUS is the drainage of the pancreatic and biliary ducts that should be done only after ERCP failure in a tertiary care center. And can be done through the stomach or the duodenum with a rendez vous procedure when it is possible to push the guide wire through the papilla or with direct eus placement of a stent <br />
  • For the biliary tree the approach can be in the left liver through the stomach or directly in the bile duct through the duodenal bulb <br />
  • One of the most important of these studies is an american multicenter study involving the injection directly into the pancreas of TNFerade which is a radiosensitizer in patients with locally advanced panc adenocarcinoma. There were no impirtant side effects and the higher doses were associated with the best results in term of disease control, progression free survival and improved survival. 4 of the 5 patients with downstaging of the disease had negative resection margins and 3 of them were alive after 2 yrs. <br />
  • One of the most important of these studies is an american multicenter study involving the injection directly into the pancreas of TNFerade which is a radiosensitizer in patients with locally advanced panc adenocarcinoma. There were no impirtant side effects and the higher doses were associated with the best results in term of disease control, progression free survival and improved survival. 4 of the 5 patients with downstaging of the disease had negative resection margins and 3 of them were alive after 2 yrs. <br />
  • Preloaded into the needle by retracting the stylet and <br />
  • And finally radiofrequency ablation that in this case is provided with cryotherapy to cool down the probe and have a better control of the RFA current. This is the first study in humans after few studies in animals that showed that the procedure was possible in about 3 third of the patients, in one there was a procedure related complicationwith fluid collection formation. On eproblem was the difficulty in having a clear visualization of the tumor margins after ablation at the follow up CT that were clearly seen in 6 patients in whom a close to significant decrease in tumor size was observed <br />

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

  • 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 􏰀 TNFerade) versus SOC alone  SOC: IV 5-FU (200mg/m2/d x 5d/wk)+Radiation (50.4 Gy), followed by gemcitabine or gemcitabine plus erlotinib maintenance therapy  TNFerade: 4x1011 PU, weekly for 5 wks  Median progression-free survival (PFS): 6.8 mos for SOC + TNFerade vs 7.0 mos for SOC (P = .51)  Multivariate analysis: EUS-TNFerade injection was a risk factor for inferior PFS Herman JM. J Clin Oncol 2013;31:886-94.
  • Implantation Therapy  Fiducial markers placement for IGRT and Cyberknife  Brachytherapy
  • Implantation Therapy Fiducial Placement  Antibiotic prophylaxis  Sterilized gold fiducials  3mm in length, 0.8mm in diameter with 19G needle  10mm in length, 0.35mm in diameter with 22G needle  Preloaded into the needle  Needle tip sealed with wax  Deployed by advancing the stylet or hydrostatic pressure with sterile water  4-6 fiducials should be deployed
  • Implantation Therapy Fiducial Placement Author (yr) No. pts Fiducial/ needle Site Success Complications Pishvaian, 2006 13 5x0.8mm 19G Mediastinal and abdominal malignancies 11/13 (85%) 1 Infection within 1 month Yang, 2009 16 5x0.8mm 19G Prostate 16/16 (100%) None Park, 2010 57 2.5x0.8mm 19G Pancreas 50/53 (94%) 1 Minor bleeding Varadarajulu, 2010 9 3x0.8mm 19G Pancreas 9/9 (100%) None Sanders, 2010 51 3x0.8mm 19G Pancreas 45/50 (90%) 1 Pancreatitis 3 Spontaneous migration DiMaio, 2010 30 10x0.35mm 22G Mediastinal and abdominal malignancies 29/30 (97%) 1 Fever
  • Implantation Therapy Brachytherapy EUS-guided implantation of radioactive 125 iodine seeds for pancreatic cancer Author (yr) Suns, 2006 Jin, 2008 No. Success Results pts. Complications 15 15/15 (100%) Partial remission in 27%, minimal 20%, stable 33%. Pain relief in 30% but not limited in time AP in 3 pts with pseudocyst formation in 2 22 22/22 (100%) Partial remission in 13.6%, stable in 45.5%. Pain relief of 1 month duration Fever in 54.5%
  • EUS-guided directed Therapy  Animal Studies  Photodynamic therapy (Chan HH. Gastrointest Endosc 2004;59:95-9; Yusuf TE. Gastrointest Endosc 2008;67:957-61)  Nd:YAG laser (Di Matteo. Gastrointest Endosc Gastrointest Endosc 2004;59:95-9. 2010;72:358-63; Di Matteo. Gastrointest Endosc 2013;78:750-5)  High-Intensity Focused Ultrasound (Hwang J. Gastrointest Endosc 2011;73:AB155)  Radiofrequency Ablation
  • EUS-guided treatment of Pancreatic ADK CryoThermal Ablation  22 pts. locally advanced panc adenocarcinoma  Flexible bipolar device that combines bipolar radiofrequency with cryogenic cooling  Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size  Successfully applied in 16 patients (73%)  Cystic fluid collection formation in one patient  In 6 patients clear definition of the tumor margins after ablation was possible and decreased tumor size was observed (p=.07) Arcidiacono PG. Gastrointest Endosc 2012; 76;1142-51.
  • Therapeutic EUS and PNENs Alcohol Ablation  78 y.o. F with     insulinoma unfit for surgery 13mm lesion in the body 8ml of 95% ethanol injected Mild transient pancreatitis Symptoms disappearance after injection  F with insulinoma refused surgery  11 and 7mm lesions in the body  2ml of 45% ethanol injected, 2 sessions  After second section, pancreatic necrosis requiring surgery