Biomarkers in Phototherapy of Barrett's Esophagus

Summary

Principal Investigator: Kenneth Wang
Affiliation: Mayo Clinic
Country: USA
Abstract: [unreadable] DESCRIPTION (provided by applicant): The purpose of this study is to define the role of biomarkers in photodynamic therapy of Barrett's esophagus. Barrett's esophagus is felt to be the predisposing condition for the most rapidly increasing cancer in Caucasian males. This is a randomized prospective trial to determine the effect of photodynamic therapy on biomarkers in Barrett's esophagus and to determine the role of biomarkers in predicting response to therapy. Preliminary studies have indicated that photodynamic therapy appears to be more effective in patients who do not have specific biomarkers. In addition, it appears that patients who undergo photodynamic therapy may have improvement in histology without improvement in biomarkers. Photodynamic therapy may induce mutations in certain genes even in normal appearing tissue. It is the goal of this protocol to determine the effect of photodynamic therapy on biomarkers that have been established to be predictors of progression to neoplasia in Barrett's esophagus. These biomarkers will include assessment of cell proliferation, ploidy, p53 expression, p53 mutations, P16 promoter hypermethylation, P16 loss, and P53 loss. Methods of assessment will include denaturing high pressure liquid chromatography, image cytometry, fluorescent in situ hybridization, and immunohistochemistry. Patients with and without biomarkers will be randomized to receive photodynamic therapy and a proton pump inhibitor or a proton pump inhibitor alone. Patients treated with photodynamic therapy will receive standard dosages of sodium porfimer (2 mg/kg) and photoradiation (130 J/cm fiber) using a balloon light delivery system. Patients will have their biomarkers assessed at six month intervals. Biological sampling will be done by biopsy and cytology to enhance sampling of the mucosal surface. In addition, primary cultures of Barrett's esophagus and squamous epithelium will be assessed for mutagenesis after photodynamic therapy in vitro to determine the rate of mutagenesis of p53. It is hoped that this study will help to define the role of photodynamic therapy in mucosal ablation of Barrett's esophagus in terms of patient selection and biomarkers that may predict response to therapy. These observations can be extended to other forms of ablative therapy in future studies.
Funding Period: 2002-09-30 - 2009-05-31
more information: NIH RePORT

Top Publications

  1. pmc Changes in screening, prognosis and therapy for esophageal adenocarcinoma in Barrett's esophagus
    Yutaka Tomizawa
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
    Curr Opin Gastroenterol 25:358-65. 2009
  2. pmc Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus
    K K Wang
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55934, USA
    Dis Esophagus 25:349-55. 2012
  3. pmc Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma
    Rami J Badreddine
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Clin Gastroenterol Hepatol 8:248-53. 2010
  4. pmc Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus
    Rami J Badreddine
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
    Gastrointest Endosc 71:697-703. 2010
  5. pmc History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus
    Stuart Jon Spechler
    VA North Texas Healthcare System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Gastroenterology 138:854-69. 2010
  6. pmc Endoscopic mucosal resection in the management of esophageal neoplasia: current status and future directions
    Vikneswaran Namasivayam
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Gastroenterol Hepatol 8:743-54; quiz e96. 2010
  7. pmc Endoscopic mucosal resection and endoscopic submucosal dissection in esophageal and gastric cancers
    Kenneth K Wang
    Barrett s Esophagus Unit, Mayo Clinic, Rochester, Minnesota 55905, USA
    Curr Opin Gastroenterol 26:453-8. 2010
  8. doi Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis
    V L Owens
    Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Dis Esophagus 25:33-9. 2012
  9. pmc Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus
    Ngozi I Okoro
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Gastroenterol Hepatol 10:150-4. 2012
  10. pmc Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett's esophagus
    Ganapathy A Prasad
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Gastroenterology 137:815-23. 2009

Scientific Experts

  • Kenneth Wang
  • S J Spechler
  • Fumiaki Sato
  • Ganapathy A Prasad
  • Lori S Lutzke
  • Lynn S Borkenhagen
  • Navtej S Buttar
  • Yutaka Tomizawa
  • Louis Michel Wongkeesong
  • Shannon M Brankley
  • Kelly T Dunagan
  • Rami J Badreddine
  • Kevin C Halling
  • Emily G Barr Fritcher
  • Jason T Lewis
  • V L Owens
  • Ngozi I Okoro
  • Vikneswaran Namasivayam
  • Wytske M Westra
  • Alan R Zinsmeister
  • Louis M Wong Kee Song
  • Rami Badreddine
  • Kausilia K Krishnadath
  • Mona S Legator
  • Benjamin R Kipp
  • Larry E Morrison
  • Schuyler O Sanderson
  • L S Lutzke
  • T C Smyrk
  • D A Katzka
  • Dennis A Wigle
  • Hamza M Abdulla
  • Louis Michel Wong Kee Song
  • Tsung Teh Wu
  • Thomas J Sebo
  • Jesse S Voss
  • Kelly Dunagan
  • Michael B Campion
  • Ann M Joyce
  • Michael L Kochman
  • Louis M Wongkeesong
  • Lewis R Roberts
  • Andrew J LeRoy
  • Todd H Baron
  • Francis C Nichols
  • Lawrence J Burgart
  • Dylan V Miller
  • Aaron R Harwood

Detail Information

Publications29

  1. pmc Changes in screening, prognosis and therapy for esophageal adenocarcinoma in Barrett's esophagus
    Yutaka Tomizawa
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
    Curr Opin Gastroenterol 25:358-65. 2009
    ..We summarize the important changes in this regard...
  2. pmc Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus
    K K Wang
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55934, USA
    Dis Esophagus 25:349-55. 2012
    ..However, even with excellent long-term results similar to surgical resection, the risk of recurrence is present in over 14% of patients, which indicates that there will be a need to continue surveillance endoscopy in these patients...
  3. pmc Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma
    Rami J Badreddine
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Clin Gastroenterol Hepatol 8:248-53. 2010
    ..We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in patients with esophageal adenocarcinoma...
  4. pmc Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus
    Rami J Badreddine
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
    Gastrointest Endosc 71:697-703. 2010
    ..The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined...
  5. pmc History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus
    Stuart Jon Spechler
    VA North Texas Healthcare System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Gastroenterology 138:854-69. 2010
    ..In this report, we review historical, molecular, and endoscopic therapeutic aspects of Barrett's esophagus that are of interest to clinicians and researchers...
  6. pmc Endoscopic mucosal resection in the management of esophageal neoplasia: current status and future directions
    Vikneswaran Namasivayam
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Gastroenterol Hepatol 8:743-54; quiz e96. 2010
    ..Training requirements to achieve proficiency in endoscopic mucosal resection as well as potential quality measures to assess competence also are proposed in this review...
  7. pmc Endoscopic mucosal resection and endoscopic submucosal dissection in esophageal and gastric cancers
    Kenneth K Wang
    Barrett s Esophagus Unit, Mayo Clinic, Rochester, Minnesota 55905, USA
    Curr Opin Gastroenterol 26:453-8. 2010
    ..This is an area that has rapidly advanced in terms of new procedures and techniques with a large body of outcomes that support their use...
  8. doi Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis
    V L Owens
    Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Dis Esophagus 25:33-9. 2012
    ..Ablation for Barrett's dysplasia can be followed rarely by eosinophil infiltrates with a histological resemblance to allergy-based eosinophilic esophagitis, but lacking dysphagia. The pathophysiology is unknown...
  9. pmc Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus
    Ngozi I Okoro
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Gastroenterol Hepatol 10:150-4. 2012
    ..We compared complications and histologic outcomes between patients who had EMR before RFA and those who received only RFA...
  10. pmc Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett's esophagus
    Ganapathy A Prasad
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Gastroenterology 137:815-23. 2009
    ..Long-term outcomes of patients treated endoscopically and surgically for mucosal EAC are unknown. We compared long-term outcomes of patients with mucosal EAC treated endoscopically and surgically...
  11. pmc Endocytoscopy in esophageal cancer
    Yutaka Tomizawa
    St Mary s Hospital, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Gastrointest Endosc Clin N Am 19:273-81. 2009
    ..Endocytoscopy is a new imaging and magnification technology. It has been developed for observation of cellular structure and applied in the esophageal cancer. In this article we summarize the important aspects of this new modality...
  12. pmc Screening, surveillance, and prevention for esophageal cancer
    Yutaka Tomizawa
    Barrett s Esophagus Unit, Alfred Main, Gastroenterology Diagnostic Unit, St Mary s Hospital, 200 2nd Street SW, Rochester, MN 55905, USA
    Gastroenterol Clin North Am 38:59-73, viii. 2009
    ..Recently developed biomarkers such as FISH and improved imaging techniques, may help overcome current problems and provide improved screening and surveillance for esophageal cancer...
  13. pmc Biomarkers in gastrointestinal cancers
    Rami Badreddine
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, St Mary s Hospital, Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Gastroenterol 103:2106-10. 2008
  14. pmc Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus
    Ganapathy A Prasad
    Division of Gastroenterology and Hepatology, 200 First Street SW, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Clin Gastroenterol Hepatol 4:173-8. 2006
    ..Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions...
  15. pmc The development of a fluorescence in situ hybridization assay for the detection of dysplasia and adenocarcinoma in Barrett's esophagus
    Shannon M Brankley
    Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN 55902, USA
    J Mol Diagn 8:260-7. 2006
    ....
  16. pmc Esophageal adenocarcinoma
    Kenneth K Wang
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Clin Gastroenterol Hepatol 4:1221-4. 2006
  17. ncbi Endoscopic therapy in patients with Barrett's esophagus and portal hypertension
    Ganapathy A Prasad
    Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Gastrointest Endosc 65:527-31. 2007
    ..Endoscopic mucosal resection has been used to stage and treat early neoplasia in Barrett's esophagus. The ability to do this in the setting of portal hypertension has not been reported...
  18. pmc Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus
    Ganapathy A Prasad
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Gastroenterology 132:1226-33. 2007
    ..Critical information regarding overall survival of patients followed up long-term after these therapies is lacking. Our aim was to compare the long-term survival of patients treated with PDT with patients treated with esophagectomy...
  19. ncbi Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma
    Ganapathy A Prasad
    Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
    Clin Gastroenterol Hepatol 5:743-8. 2007
    ..Recent studies have shown a survival advantage using photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma. Factors associated with increased survival after PDT are unknown...
  20. pmc Significance of neoplastic involvement of margins obtained by endoscopic mucosal resection in Barrett's esophagus
    Ganapathy A Prasad
    Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Am J Gastroenterol 102:2380-6. 2007
    ..The aim of this study was to assess the accuracy of tumor staging by EMR using esophagectomy as the standard...
  21. pmc Endoscopic confocal microscopy: imaging to facilitate the dawn of endoluminal surgery
    Kenneth K Wang
    Clin Gastroenterol Hepatol 5:1259-60. 2007
  22. pmc Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features
    Fumiaki Sato
    Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 3:e1890. 2008
    ..In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency...
  23. pmc Utility of biomarkers in prediction of response to ablative therapy in Barrett's esophagus
    Ganapathy A Prasad
    Barrett s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Gastroenterology 135:370-9. 2008
    ..We aimed to determine if biomarkers known to be associated with neoplasia in BE can predict loss of dysplasia in patients treated with ablative therapy for HGD/intramucosal cancer...
  24. pmc Correlation of histology with biomarker status after photodynamic therapy in Barrett esophagus
    Ganapathy A Prasad
    Barrett Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Cancer 113:470-6. 2008
    ..The objectives of the current study were 1) to assess biomarkers in a prospective cohort of patients with HGD/mucosal cancer before and after PDT and 2) to correlate biomarker status after PDT with histology...
  25. pmc A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus
    Emily G Barr Fritcher
    Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Hum Pathol 39:1128-35. 2008
    ..Additional studies are needed to further evaluate the clinical use of FISH...
  26. pmc Current Strategies in the management of Barrett's esophagus
    Kenneth K Wang
    Division of Gastroenterology and Hepatology, Main Alfred Gastroenterology Unit, Saint Mary s Hospital, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA
    Curr Gastroenterol Rep 7:196-201. 2005
    ..Promising future tools and techniques for surveillance and treatment are described in this review...