Non-invasive competition for EUS (US, CE-US, CT, MRI and PET/CT): the radiologist point of view

Transcription

1 UNIVERSITA DEGLI STUDI DI TORINO DIPARTIMENTO DI DISCIPLINE MEDICO-CHIRURGICHE SEZIONE DI RADIODIAGNOSTICA CATTEDRA DI RADIOLOGIA DIRETTORE: PROF. G. GANDINI Scientific Session III: biliopancreatic EUS The management of patients with pancreatic cancer: a difficult challenge and multidisciplinary approach Non-invasive competition for EUS (US, CE-US, CT, MRI and PET/CT): the radiologist point of view Giovanni Gandini Maria Cristina Martina Torino, September 15 th 2007

2 .introduction PANCREATIC CANCER At the diagnosis Only 20-30% are considered candidates for curative surgery 80% non resectable for extrapancreatic spread, vascular invasion, limphnodes and distant metastasis, peritoneal carcinosis The patient s prognosis relies not only on early diagnosis, but also on accurate tumor staging, which is crucial to indicate the most appropriate treatment

3 .introduction PANCREATIC CANCER Early diagnosis and assessment of tumor resectability are the important tasks for diagnostic imaging. Head lesions early signs Body and tail lesions lesions late signs

4 IMAGING Role of the radiologist Lesion detection Differential diagnosis Staging assessment of resectability Pancreatic cancer Follow-up

5 IMAGING US Contrast Enhanced US (CEUS) CT Multidetector helical CT(MDCT) with protocols directed at optimal imaging of the pancreas MR c. e. MRI: Gadolinium Mangafodipir MR-angiography MRCP PET-CT

6 US 1 st investigation IMAGING Hypoechoic (with necrotic areas) 97% IDENTIFICATION of the lesion Sensitivity 56-96% Tumors > 3 cm Specificity > 95% ( Hesse 1982 Del Maschio 1991 ) IDENTIFICATION of biliary obstruction 92-98%

7 Minniti S, Bruno C, Procacci C et al Sonography versus helical CT in identification and staging of pancreatic ductal adenocarcinoma. J Clin Ultrasound May;31(4): US 64 pz with pancreas adenocarcinoma mean tumor size3.2 cm (range cm) Tumor identification US 61/64 ( sens 95.3%) CT 57/64 ( sens 89.1%) Overall Resectability US 81.4% prediction (43 pz) CT 86% CT Technique Arterial phase 5 mm slice thickness Portal phase 8 mm slice thickness! Encasement SMA US 95.3% CT 88.4% Hepatic mts US and CT 86% Celiac trunk involvement US and CT 100% CHA involvement US 90.7% CT 95.3% Portal vein involvement US 88.4% CT 93.0% The ability of US to detect subtle differences in echogenicity between the normal parenchima and the tumor results in a tumor detection capability superior to that of CT sonography was clearly more accurate than CT in diagnosing ductal adenocarcinoma of the pancreas. US was more accurate than CT in delineating the tumor, as accurate as CT in preoperative staging, with acceptable low incidence of poor-quality sonographic examinations.

8 Harmonic imaging, 3D ultrasonography, Color and Power Doppler US have brought dramatic developements in the diagnosis of pancreatic cancer. Hirooka Y et al Recent advances in US diagnosis of pancreatic cancer. Hepatogastroenterology Jul-Aug;48(40): US After injection of air-based contrast agent a clear difference was seen between a mass due to chronic focal pancreatitis and one due to pancreatic carcinoma, when the pattern of vascularization was considered. Lack of vascularization was never observed in pancreatic carcinomas, which showed a statistically significant larger number of vessels in comparison with chronic focal pancreatitis.

9 Rickes S, Monkenmuller K, Malfertheiner P Contrast-enhanced Ultrasound in the Diagnosis of Pancreatic Tumors JOP J Pancreas 2006; 7 (6): CEUS pancreatic tumors have a different vascularization pattern in echo-enhanced ultrasound. Sensitivity and specificity of echo-enhanced sonography in diagnosing the degree of differentation of pancreatic masses are equal to, or greater than 85% and 90% respectively. Lesion Sensitivity Specificity PPV NPV Adenocarcinoma (137 patients investigated) Pancreatitis (137 patients investigated) Neuroendocrine tumor (138 patients investigated) Cystic tumor (31 patients investigated) 87% 94% 89% 93% 85% 99% 97% 94% 94% 96% 76% 99% % % % % D Onofrio M, Zamboni G, Faccioli N, Capelli P, Pozzi Mucelli R Ultrasonography of tha pancreas Contrast-enhanced imaging Abdominal Imaging 2007; 32: ductal adenocarcinoma shows poor enhancement in all CEUS phases... CEUS can be used to better identify lesions respect to conventional US or to characterize pancreatic lesions already visible at US. New trends must be further developed: - use of CEUS enhancement as a prognostic factor, thanks to its correlation with pathological features; - using MBs as a vehicle for targeted therapies (still in the first phases of study)

10 limitations US IDENTIFICATION non explorability (15-25% ) patient body habitus, overlying bowel gas (20%), former surgery, etc. operator expertise more recent techniques not freely available at present STAGING locoregional extension (peripancreatic fat, stomach, colon, kidney, spleen) regional lymph node involvement (hepatic hilum, periaortic, retrogastric) vascular invasion distant metastases

11 IMAGING CT and MRI are the imaging techniques that have changed the clinical and surgical approach in the diagnosis, and especially, in the staging of pancreatic tumors Catalano C, laghi A, Fraioli F, Passariello R et al Pancreatic carcinoma: the role of high-resolution multislice spiral CT in the diagnosis and assessment of resectability. Eur Radiol Jan;13(1):

12 MRI IMAGING vs CT Higher contrast resolution Multiplanar acquisitions Intolerance to iodine cm Renal failure (?) Lower spatial resolution MRCP Cholangiografic study of biliary and pancreatic ducts 124 pz ERCP MRCP sensitivity specificity 70% 94% 84% 97% Adamek HE et al Lancet 2000 Accurate for diagnosing obstruction, less in identifying malignant features No first-line tool for diagnosing a pancreatic malignancy

13 MRCP IMAGING

14 HOW? MRI Dynamic study with intravascular c.m. (gadolinium chelates Gd-DTPA) To depict tissue vascularity and vascular details Morphologic study with tissue specific c.m. (Mangafodipir o Mn-DPDP o Teslascan) FP

15 Zanello A, Nicoletti R, Brambilla P, Del Maschio A Magnetic resonance with manganese-dpdp (mangafodipir) of focal solid pancreatic lesions. Radiol Med (Torino) Sep;108(3): Shima W, Fugger R, Schober E Diagnosis and staging of pancreatic cancer: comparison of mangafodipir trisodium-enhanced MR imaging and contrastenhanced helical hydro-ct. AJR Am J Roentgenol Schima w, Fugger R Evaluation of focal pancreatic masses: comparison of mangafodipir-enhanced MR imaging and contrast-enhanced helical CT. Eur Radiol Dec;12(12): Boraschi P, Donati F, Gigoni R et al. Mangafodipirtrisodium-enhanced MR imaging of pancreatic disease. Eur Radiol. 2006; (16): Focal lesions detection Overall accuracy 93 % (Zanello pts) 92 % (Boraschi pts) MRI sensitivity 100% vs CT 94% (Shima pts) Higher sensitivity for 2 cm tumors MRI 100% (8/8) vs CT 75% (Shima pts) Increased sensitivity in the detection of liver metastases (7/8 pts with MR- 4/8 pts with CT) (Shima pts)

16 Focal lesion characterization, in particular a reliable differentiation between focal chronic pancreatitis and cancer, still remains an unresolved challenge

17 Tajima Y, Kurori T, Tsutsumi R et al. Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor forming pancreatititis: Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging World J Gastroenterol 2007 Feb;13 (6): Pancreatic time-signal intensity curve from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially in patients with longstanding chronic pancreatitis. The TIC profile of a carcinoma always depicted the slowest rise to a peak there was an overlap in the TIC profile between pancreatic carcinoma and tumor-forming pancreatitis in this study Ductal carcinoma in chronic pancreatitis Chronic pancreatitis

18 Cho SG,Lee DH, Lee KY et al. Differentiation of Chronic Focal Pancreatitis From Pancreatic Carcinoma by In Vivo Proton Magnetic Resonance Spectroscopy J Comput Assist Tomogr 2005; 29 (2): patients the most significant difference between the 1 H-MRS features of chronic focal pancreatitis and pancreatic carcinoma was in the lipid content. The 1 H-MRS spectra of chronic focal pancreatitis showed significantly less lipid than did spectra of pancreatic carcinoma (that might be explained by differencies in fibrous tissue content). there was an overlap in the distribution of ratios between these two entities. further studies with larger sample sizes and better techniques of MRS are needed to determine more specific criteria. Pancreatic carcinoma Chronic pancreatitis

19 MR Imaging suggestions MRI Problem-solving modality (equivocal findings at US or CT) S-MRCP (evaluation is needed) Contraindication to Ionic contrast media/x-ray exposure Mn-DPDP Proton MR spectroscopy (further studies needed) Michl P, Pauls S, Gress TM. Evidence-based diagnosis and staging of pancreatic cancer. Best practice and research Clinical Gastroenterology 2006; 20(2): Shima W AJR 2002; 12: The pancreas, modern diagnosis imaging Verona, September 8, 2005

20 IMAGING.Although CT and MRI sensitivity in the identification of the tumor are considered equivalent, the greater availability of CT and the technological developement of the last years, have made this last the method of choice in the study of pancretic disease Reviewer 1 Reviewer 2 Sensibility Specificity Accuracy Sensibility Specificity Accuracy Helical CT 96% 81% 88% 83% 89% 86% Dynamic MR 80% 78% 79% 95% 71% 81% Nishiharu T et al Local extension of pancreatic carcinoma: assessment with thin-section helical CT versus breath-hold fast MR imaging--roc analysis Radiology Aug;212(2):

21 MDCT IMAGING Axial scans Fast acquisition in a single breath hold Larger volumes Thin collimation (1-3 mm) Optimises contrast agent infusion Multiphasic technique Better parenchimal enhancement Post-processing 3D recontructions Angio CT of peripancreatic vessels High resolution Isotropic voxel Catalano C, L aghi A, Fraioli F, Passariello R et al Pancreatic carcinoma: the role of high-resolution multislice spiral CT in the diagnosis and assessment of resectability. Eur Radiol Jan;13(1):

22 DIAGNOSIS MDTC Poor vascularization Hypodense in dual-phase acquisition ( pancreatic and portal) Change in texture and contour Sensitivity 97% - Specificity 80% - Accuracy 96% (1.3-6 cm) Catalano C, Laghi A Passariello R et al Eur Radiol Jan;13(1): the developement of modern multiphase thin slice helical CT has markedly improved the sensitivity of CT for the detection of tumors < 2 cm, reaching values comparable to those obtianed with EUS by an expert endoscopist (sensitivity 72-77%, specificity 100%) Bronstein YL, Loyer EM, Kaur H et al Detection of small pancreatic tumors with multiphasic helical CT. AJR, :

23 however demonstration of carcinoma < 1 cm maybe almost impossible at present. MDTC INDIRECT SIGNS Pancreatic atrophy Wirsung dilatation MBD dilatation Saisho H, Yamaguchi T Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography. Pancreas 2004 Apr;28(3): if possible MDCT should be performed prior to therapeutic stenting of biliary obstructions, since stents in situ frequently limit the diagnostic value of this imaging technique. Michl P, Pauls S, Gress TM. Evidence-based diagnosis and staging of pancreatic cancer. Best practice and research Clinical Gastroenterology 2006; 20(2):

24 ...if possible, it is important to know if there is clinical suspicion of endocrine tumors, since they particularly take advantage of dedicated, dynamic MDCT protocols. MDCT

25 Distant metastases sct sensitivity 75% - 87 % Staging MRI sensitivity 93.5% PET sensitivity 70% 60% of patients SITE Liver 30-60% Peritoneum 7-10% Lungs Adrenal glands Kidneys Bones PATTERN Hypovascular

26 Vascular infiltration in the absence of distant metastatic disease, vascular invasion becomes the most common criterion for unresectability. Lu and O Malley Classification Prokesch R et al Eur Radiol 2003 Ellsmere J et al Surg Endosc. 2005;19(3): Celiac Trunk Hepatic Artery Superior Mesenteric Artery Superior Mesenteric Vein Portal Vein sct Accuracy 70-95% ( Lu % ; O Malley % ) Mazzeo S, Cappelli C, Caramella D et al Evaluation of vascular infiltration in resected patients for pancreatic cancer: comparison among multidetector CT, intraoperative findings and histopathology. Abdom Imaging Staging MDCT Sensitivity and specificity 94% ( Karmazanovsky 2005) 37pts -52vessels MDCT sensitivity 90%

27 RESECTABILITY ASSESSMENT...according to the literature CT has been shown to be almost 100% accurate in predicting unresectable disease. However the positive predictive value of the test is low and approximately 21-55% of patients predicited to have resectable disease on CT turn out to have unresectable lesions at laparotomy (vascular invasion, small peritoneal implants, small hepatic metastases) Takhar AS Recent developements in diagnosis of pancreatic cancer Preoperative Staging and Tumor resectability Assessment of Pancreatic Cancer BMJ. 2004; 329: Li H, Zeng MS, Zhou KR et al. Pancreatic adenocarcinoma: the different CT criteria for peripancreatic major arterial and venous invasion. J Comput Assist Tomogr Mar-Apr;29(2): Vargas R, Nino-Murcia MDCT in Pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol Feb;182(2): The first results of MDCT possibilities to improve the tumor resectability assessment are encouraging. the problem of undetected metastases to the liver and the peritoneum remains. (Vargas 2004)

28 RESECTABILITY ASSESSMENT Helical CT is the mainstay for pancreatic cancer staging, with the best figures in the evaluation of extent of primary tumor, locoregional extension, vascular invasion and metastatic spread. Although MRI was said to have potential advantages, such as high tissue contrast that might increase the conspicuity of lesions and manipulating pulse sequence parameters to improve depiction of vascular structures, it seems not to surpass helical CT in pancreatic cancer staging. Soriano A, Castells A Preoperative Staging and Tumor resectability Assessment of Pancreatic Cancer: Prospective Study Comparing Endoscopic Ultrasonography, HelicalComputed Tomography, Magnetic Resonance Imaging and Angiography Am J of Gastroenterology. 2004:

29 Bipat S, Phoa SSKS, van Delden OM Ultrasonography, Computed Tomography and Magnetic Resonance Imaging for Diagnosis and Determining Resectability of Pancreatic Adenocarcinoma: A Meta-Analysis. J Comput Assist Tomogr. 2005; 29: articles with at least 20 patients (total 7405 patients) Helical CT is preferable as an imaging modality for the diagnosis and determination of resectability of pancreatic adenocarcinoma Imaging Modality Data Sets/ Number of Patients Sensitivity (95% CI) Specificity (95% CI) Diagnosis US 14/ % (69, 82) 75% (51, 89) MRI 11/583 84% (78, 89) 82% (67, 92) Conventional CT 20/ % (81, 89) 79% (60, 90) Helical CT 23/959 91% (86, 94) 85% (76, 91) Resectability US 6/ % (68, 91) 63% (45, 79) MRI 7/516 82% (69, 91) 78% (63, 87) Conventional CT 12/ % (74, 88) 76% (61, 86) Helical CT 32/ % (76, 85) 82% (77, 87)

30

31

32 RECURRENCE (pancreaticoduodenectomy)

33 ...despite MDCT limitations 1. Preoperative detection of small metastases in the liver, lymph nodes *, peritoneal and omental involvement (pre-operatory laparoscopy) * MDCT Sensitivity 48.6% Saisho H, Impossibility to detect isodense tumors 3. Differential diagnosis between adenocarcinoma and focal chronic pancreatitis is difficult, frequently impossible 4. Early diagnosis Ellsmere J, Mortele K, Sahani D Does multidetector-row CT eliminate the role of diagnostic laparoscopy in assessing the resectability of pancreatic head adenocarcinoma? Surg Endosc Mar;19(3): Scaglione M, Pinto A, Romano S et al Using multidetector row computed tomography to diagnose and stage pancreatic carcinoma: the problems and the possibilities. JOP ; 6(1):1-5.

34 Calculli L, Pezzilli R, Gavelli G et al The imaging of pancreatic exocrine solid tumors: the role of computed tomography and positron emission tomography. JOP 2007; 8(1 Suppl.): CT-PET Combines the anatomical information of sct with the functional information of a PET scanner Possibility of evaluating the entire body Better identifies the presence of distal metastases Orlando LA, Kulasingam Si, Matchar DB Metanalisis: the dtetection of pancreatic malignancy with positron emission tomography. Aliment Pharmacol Ther. 2004; 20: Meta-analysis on 17 studies: Sensitivity % Specificity %

35 Sendler A, Avril N, Helmberger H et al Preoperative evaluation of pancreatic masses with positron emission tomography using 18-F-Fluorodeoxiglucose: diagnostic limitations World J Surg 2000; 24: CT-PET specificity of this imaging technique is of limited value because the hypermetabolic cells found in chronic pancreatitis or other inflammatory conditions (previous ge surgery, acute exacerbation of chronic p., recent interventional procedures: stents) may lead to false positive diagnosis. (Diabetes may lead to false negatives) Sahani DV, Kalva SP, Fishman AJ et al Detection of liver metastases from adenocarcinoma of the colon and pancreas: comparison of mangafodipir trisodium enhanced liver MRI and whole body FDG-PET. AJR 2005; 185: MRI detected significantly more and smaller metastases than FDG CT- PET, especially when smaller than 1 cm. Orlando LA, Kulasingam Si, Matchar DB Metanalysis: the detection of pancreatic malignancy with positron emission tomography. Aliment Pharmacol Ther. 2004; 20: although adding FDG-PET to the diagnostic work-up may enhance the diagnosis of pancreatic malignancy further evaluation (combination of cect), with prospective studies and cost-effectiveness analysis is needed to clarify the appropriate role...

36 CONCLUSIONS the radiologist s point of view MDCT Technological evolution is a fact and cannot be stopped... MRI PET-CT.but is not always the solution to all of our problems.

37 Schima w, Fugger R Evaluation of focal pancreatic masses: comparison of mangafodipirenhanced MR imaging and contrast-enhanced helical CT. Eur Radiol Dec;12(12): Soriano A, Gines MA et al Preoperative Staging and Tumor Resectability Assessment of Pancreatic Cancer: Prospective Study Comparing Endoscopic Ultrasonography, Helical Computed Tomography, Magnetic Resonance Imaging and Angiography American Journal of Gastroenterology 2004 : MDCT EUS CEUS CT-PET Michl P, Pauls S, Gress TM. Evidence-based diagnosis and staging of pancreatic cancer. Best practice and research Clinical Gastroenterology 2006; 20(2): Currently, no single best imaging modality for evaluation of pancreatic disease exists. Helical CT and EUS are the most useful individual imaging techniques in the staging of pancreatic cancer. In those cases with potentially resectable tumors a sequential approach consisting of helical CT as an initial test and EUS as a confirmatory technique seems to be the most reliable, cost-effective and accurate strategy. MRI with MRI-angiography, MRCP, PET-CT are additional modalities which might give further information in cases of equivocal findings by MDCT and EUS.