Clinical trial NCT00909103: Endoscopic Ultrasound Elastography in Pancreatic Masses
Official title: Computer-aided Diagnosis of Endoscopic Ultrasound Elastography Used in the Differentiation of Focal Pancreatic Masses
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pancreatic Adenocarcinoma
Chronic Pancreatitis
Keywords: Endoscopic Ultrasound Elastography
Pancreatic adenocarcinoma
Chronic Pancreatitis
Lead sponsor: University of Medicine and Pharmacy Craiova
Sponsor class: OTHER
Collaborators: name: University Hospital, Gentofte, Copenhagen
name: Odense University Hospital
name: Institut Paoli-Calmettes
name: San Raffaele University Hospital, Italy
name: UCL (Univ), Brussels, Belgium
name: Glasgow Royal Infirmary
name: Caritas-Krankenhaus Bad Mergentheim
name: University of Bergen
name: University of Witten/Herdecke
name: Newcastle-upon-Tyne Hospitals NHS Trust
First posted: 2009-05-27
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The diagnosis of chronic pancreatitis will be based on the clinical information (history of alcohol abuse, previous diagnosis of chronic pancreatitis or diabetes mellitus), as well as a combination of imaging methods (ultrasound, CT and EUS). At least four criteria of chronic pancreatitis during EUS will be considered for the positive diagnosis.

A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass. The diagnoses obtained by EUS-FNA will be further verified either by surgery or during a clinical follow-up of at least 6 months.

Brief summary: The aim of the study is to assess elastography during EUS examinations of focal pancreatic masses, and to consequently differentiate benign versus malignant pancreatic masses in a prospective multi-center design.

Detailed description: Ultrasound elastography is a recent ultrasound method used for the calculation of tissue elasticity distribution in real-time. The method allows the reconstruction of tissue elasticity (i.e. the elasticity modulus) and reveals directly the physical properties of the tissue, consequently showing different tissue hardness patterns that are determined by diseases. Tissue elastography can be easily performed real-time with conventional probes, including the linear EUS probes used for the examination of the pancreas. The calculation of tissue elasticity distribution is performed in real-time and the examination results are represented as transparent overlay colour images overimposed on the conventional gray-scale B-mode images.

Ultrasound elastography was previously used for the diagnosis of breast lesions, prostate cancer and thyroid nodules. However, the value of endoscopic ultrasound elastography for the diagnosis of pancreatic focal masses is not clear for the current moment, as some authors couldn't differentiate benign and malignant pancreatic tumors. Moreover, the intense fibrotic reaction and calcifications in chronic pancreatitis induce strain differences, and it is not clear if elastography is sensitive enough to detect them.

The study protocol is based on a semi-quantitative approach of EUS elastography data (movies) consisting of characterization of manually user-defined regions of interest, based on the hue histograms of the individual focal masses. Due to the inherent bias induced by selection of images from a dynamic sequence of EUS elastography, we have previously reported on the utility of using computer-aided diagnosis by averaging images from a dynamic sequence of EUS elastography. A special plugin (based on the ImageJ software, NIH, Bethesda, MD, USA) is used to compute hue histograms on average EUS elastography images, while the hue histograms values for each patient (0 to 255 values) are further used to classify the patients with benign and malignant lesions.

Ultrasound elastography will be performed during an usual EUS examination (7.5 MHz frequency), with two movies of 10 seconds recorded on the embedded HDD in order to minimize variability and to increase repeatability of acquisition. A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the elastography image on the left side will be used. The region of interest will be preferably larger than the focal mass, in order to include the surrounding structures. In order to minimize the human bias, all the post-processing and computer analysis of digital movies will be performed within the IT Center in Craiova, with all programmers and statisticians being blinded to the clinical, pathological and imaging data, with the exception of the average hue histogram values calculated from a second region of interest manually traced around the focal mass.

The study design is prospective, blinded and multi-center, comparing endoscopic ultrasound elastography (EUS-EG) results for the detection and characterization of focal pancreatic masses by using artificial intelligence techniques, in comparison with the gold standard represented by pathology. The study will be performed with the approval of the institutional board review of each center.

Eligibility criteria: Inclusion criteria

* Patients diagnosed with solid pancreatic tumor masses, with cytological / histological confirmation
* Age 18 to 80 years old, men or women
* Signed informed consent for EUS with elastography and FNA biopsy

Exclusion criteria

* Prior surgical treatment with curative intent or chemo-radiotherapy
* Patients diagnosed with mucin producing tumors, pancreatic cystic tumors, etc.

Primary outcomes:
measure: Value of endoscopic ultrasound elastography for the differential diagnoses of pancreatic masses.
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme University
city: Brussels
country: Belgium
facility: Universite Chatolique Louvain
city: Copenhagen
country: Denmark
facility: Gentofte University Hospital
city: Odense
country: Denmark
facility: University Hospital
city: Marseille
country: France
facility: Institute Paoli Calmettes
city: Bad Mergentheim
country: Germany
facility: Caritas-Krankenhaus
city: Bochum
country: Germany
facility: St. Josef Hospital
city: Gera
country: Germany
facility: SRH Klinik
city: Mainz
country: Germany
facility: University Clinic Mainz
city: Wiesbaden
country: Germany
facility: Dr.Horst-Schmidt-Klinik
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, University of Witten/Herdecke
city: Milan
country: Italy
facility: Hospital San Raffaele
city: Rotterdam
country: Netherlands
facility: Erasme Medisch Centrum
city: Bergen
country: Norway
facility: University of Haukeland
city: Craiova
country: Romania
facility: University of Medicine and Pharmacy Craiova
city: Santiago
country: Spain
facility: University Hospital Santiago
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Newcastle
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals
Study officials:
affiliation: University of Medicine and Pharmacy Craiova, Romania
name: Adrian Saftoiu, Professor
role: STUDY_DIRECTOR
References:
citation: Frey H. [Realtime elastography. A new ultrasound procedure for the reconstruction of tissue elasticity]. Radiologe. 2003 Oct;43(10):850-5. doi: 10.1007/s00117-003-0943-2. German.
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citation: Itoh A, Ueno E, Tohno E, Kamma H, Takahashi H, Shiina T, Yamakawa M, Matsumura T. Breast disease: clinical application of US elastography for diagnosis. Radiology. 2006 May;239(2):341-50. doi: 10.1148/radiol.2391041676. Epub 2006 Feb 16.
citation: Miyanaga N, Akaza H, Yamakawa M, Oikawa T, Sekido N, Hinotsu S, Kawai K, Shimazui T, Shiina T. Tissue elasticity imaging for diagnosis of prostate cancer: a preliminary report. Int J Urol. 2006 Dec;13(12):1514-8. doi: 10.1111/j.1442-2042.2006.01612.x.
citation: Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab. 2007 Aug;92(8):2917-22. doi: 10.1210/jc.2007-0641. Epub 2007 May 29.
citation: Janssen J, Schlorer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc. 2007 Jun;65(7):971-8. doi: 10.1016/j.gie.2006.12.057.
citation: Saftoiu A, Vilmann P, Ciurea T, Popescu GL, Iordache A, Hassan H, Gorunescu F, Iordache S. Dynamic analysis of EUS used for the differentiation of benign and malignant lymph nodes. Gastrointest Endosc. 2007 Aug;66(2):291-300. doi: 10.1016/j.gie.2006.12.039.
citation: Saftoiu A, Vilmann P, Gorunescu F, Janssen J, Hocke M, Larsen M, Iglesias-Garcia J, Arcidiacono P, Will U, Giovannini M, Dietrich CF, Havre R, Gheorghe C, McKay C, Gheonea DI, Ciurea T; European EUS Elastography Multicentric Study Group. Efficacy of an artificial neural network-based approach to endoscopic ultrasound elastography in diagnosis of focal pancreatic masses. Clin Gastroenterol Hepatol. 2012 Jan;10(1):84-90.e1. doi: 10.1016/j.cgh.2011.09.014. Epub 2011 Oct 1.
citation: Saftoiu A, Vilmann P, Gorunescu F, Janssen J, Hocke M, Larsen M, Iglesias-Garcia J, Arcidiacono P, Will U, Giovannini M, Dietrich C, Havre R, Gheorghe C, McKay C, Gheonea DI, Ciurea T; European EUS Elastography Multicentric Study Group. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy. 2011 Jul;43(7):596-603. doi: 10.1055/s-0030-1256314. Epub 2011 Mar 24.