OBJECTIVES: Barrett's esophagus (BE) surveillance with white-light endoscopy and quadrantic biopsies (Seattle protocol) is resource intensive and limited by sampling error. Previous work suggests that autofluorescence imaging (AFI) in combination with a molecular panel might reduce the number of biopsies, but this was not sufficiently sensitive for low-grade dysplasia, now a point for endoscopic intervention. Here we used AFI to direct narrow-field imaging tools for real-time optical assessment of dysplasia and biopsies for a biomarker panel. We compared the new diagnostic algorithm with the current standard. METHODS: A total of 55 patients with BE were recruited at a single tertiary referral center. Patients underwent high-resolution endoscopy followed by AFI. AFI-targeted areas (n=194) were examined in turn by narrow-band imaging with magnification (NBIz) and probe-based confocal laser endomicroscopy (pCLE). Biopsies were taken from AFI-targeted areas and tested using an established molecular panel comprising aneuploidy plus cyclin A and p53 immunohistochemistry. RESULTS: In the per-patient analysis the overall sensitivity and specificity of AFI-targeted pCLE were 100% and 53.6% for high-grade dysplasia/intramucosal cancer and 96.4% and 74.1% for any grade of dysplasia, respectively. NBIz had equal specificity for dysplasia detection (74.1%), but significantly lower sensitivity (57.1%) than pCLE. The time required to perform AFI-targeted pCLE was shorter that that taken by the Seattle protocol (P=0.0004). We found enrichment of molecular abnormalities in areas with optical dysplasia by pCLE (P<0.001), regardless of histologic dysplasia. The addition of the 3-biomarker panel reduced the false positive rate of pCLE by 50%, leading to sensitivity and specificity for any grade of dysplasia of 89.2% and 88.9%, respectively. CONCLUSIONS: The combination of pCLE on AFI-targeted areas and a 3-biomarker panel identifies patients with dysplasia.
OBJECTIVES: Barrett's esophagus (BE) surveillance with white-light endoscopy and quadrantic biopsies (Seattle protocol) is resource intensive and limited by sampling error. Previous work suggests that autofluorescence imaging (AFI) in combination with a molecular panel might reduce the number of biopsies, but this was not sufficiently sensitive for low-grade dysplasia, now a point for endoscopic intervention. Here we used AFI to direct narrow-field imaging tools for real-time optical assessment of dysplasia and biopsies for a biomarker panel. We compared the new diagnostic algorithm with the current standard. METHODS: A total of 55 patients with BE were recruited at a single tertiary referral center. Patients underwent high-resolution endoscopy followed by AFI. AFI-targeted areas (n=194) were examined in turn by narrow-band imaging with magnification (NBIz) and probe-based confocal laser endomicroscopy (pCLE). Biopsies were taken from AFI-targeted areas and tested using an established molecular panel comprising aneuploidy plus cyclin A and p53 immunohistochemistry. RESULTS: In the per-patient analysis the overall sensitivity and specificity of AFI-targeted pCLE were 100% and 53.6% for high-grade dysplasia/intramucosal cancer and 96.4% and 74.1% for any grade of dysplasia, respectively. NBIz had equal specificity for dysplasia detection (74.1%), but significantly lower sensitivity (57.1%) than pCLE. The time required to perform AFI-targeted pCLE was shorter that that taken by the Seattle protocol (P=0.0004). We found enrichment of molecular abnormalities in areas with optical dysplasia by pCLE (P<0.001), regardless of histologic dysplasia. The addition of the 3-biomarker panel reduced the false positive rate of pCLE by 50%, leading to sensitivity and specificity for any grade of dysplasia of 89.2% and 88.9%, respectively. CONCLUSIONS: The combination of pCLE on AFI-targeted areas and a 3-biomarker panel identifies patients with dysplasia.
Authors: Prateek Sharma; Alexander R Meining; Emmanuel Coron; Charles J Lightdale; Herbert C Wolfsen; Ajay Bansal; Monther Bajbouj; Jean-Paul Galmiche; Julian A Abrams; Amit Rastogi; Neil Gupta; Joel E Michalek; Gregory Y Lauwers; Michael B Wallace Journal: Gastrointest Endosc Date: 2011-07-13 Impact factor: 9.427
Authors: Prateek Sharma; John Dent; David Armstrong; Jacques J G H M Bergman; Liebwin Gossner; Yoshio Hoshihara; Janusz A Jankowski; Ola Junghard; Lars Lundell; Guido N J Tytgat; Michael Vieth Journal: Gastroenterology Date: 2006-08-16 Impact factor: 22.682
Authors: J M Dunn; G D Mackenzie; D Oukrif; C A Mosse; M R Banks; S Thorpe; P Sasieni; S G Bown; M R Novelli; P S Rabinovitch; L B Lovat Journal: Br J Cancer Date: 2010-05-11 Impact factor: 7.640
Authors: Nicholas J Shaheen; Prateek Sharma; Bergein F Overholt; Herbert C Wolfsen; Richard E Sampliner; Kenneth K Wang; Joseph A Galanko; Mary P Bronner; John R Goldblum; Ana E Bennett; Blair A Jobe; Glenn M Eisen; M Brian Fennerty; John G Hunter; David E Fleischer; Virender K Sharma; Robert H Hawes; Brenda J Hoffman; Richard I Rothstein; Stuart R Gordon; Hiroshi Mashimo; Kenneth J Chang; V Raman Muthusamy; Steven A Edmundowicz; Stuart J Spechler; Ali A Siddiqui; Rhonda F Souza; Anthony Infantolino; Gary W Falk; Michael B Kimmey; Ryan D Madanick; Amitabh Chak; Charles J Lightdale Journal: N Engl J Med Date: 2009-05-28 Impact factor: 91.245
Authors: David F Boerwinkel; Jasmin A Holz; Mohammed A Kara; Sybren L Meijer; Michael B Wallace; Louis-Michel Wong Kee Song; Krish Ragunath; Herbert C Wolfsen; Prasad G Iyer; Kenneth K Wang; Bas L Weusten; Maurice C Aalders; Wouter L Curvers; Jacques J G H M Bergman Journal: Clin Gastroenterol Hepatol Date: 2013-10-24 Impact factor: 11.382
Authors: Patricia C Galipeau; Xiaohong Li; Patricia L Blount; Carlo C Maley; Carissa A Sanchez; Robert D Odze; Kamran Ayub; Peter S Rabinovitch; Thomas L Vaughan; Brian J Reid Journal: PLoS Med Date: 2007-02 Impact factor: 11.069
Authors: Rebecca C Fitzgerald; Massimiliano di Pietro; Krish Ragunath; Yeng Ang; Jin-Yong Kang; Peter Watson; Nigel Trudgill; Praful Patel; Philip V Kaye; Scott Sanders; Maria O'Donovan; Elizabeth Bird-Lieberman; Pradeep Bhandari; Janusz A Jankowski; Stephen Attwood; Simon L Parsons; Duncan Loft; Jesper Lagergren; Paul Moayyedi; Georgios Lyratzopoulos; John de Caestecker Journal: Gut Date: 2013-10-28 Impact factor: 23.059
Authors: J Nwachokor; O Tawfik; M Danley; S Mathur; J House; P Sharma; L K Christenson; A Bansal Journal: Dis Esophagus Date: 2017-09-01 Impact factor: 3.429
Authors: Elena Lastraioli; Tiziano Lottini; Jessica Iorio; Giancarlo Freschi; Marilena Fazi; Claudia Duranti; Laura Carraresi; Luca Messerini; Antonio Taddei; Maria Novella Ringressi; Marianna Salemme; Vincenzo Villanacci; Carla Vindigni; Anna Tomezzoli; Roberta La Mendola; Maria Bencivenga; Bruno Compagnoni; Mariella Chiudinelli; Luca Saragoni; Ilaria Manzi; Giovanni De Manzoni; Paolo Bechi; Luca Boni; Annarosa Arcangeli Journal: Oncotarget Date: 2016-09-13