Best Treatment for Barrett’s is Surgery Bill Richards, MD FACS Professor and Chair Surgery University of South Alabama College of Medicine

Barrett’s = Intestinal Metaplasia Metaplasia = change in cell-type Squamous to specialized intestinal cells First described by Norman Barrett in 1950 Adaptive mechanism to injury

Metaplasia (no dysplasia) Disease Course Progression usually occurs but regression sometimes seen Duration of progression variable Metaplasia (no dysplasia) Low-Grade Dysplasia High-Grade Dysplasia Adenocarcinoma Ginsberg et al. In: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. 7th ed. 2002:647-671.

Risk of Adenocarcinoma in Barrett’s Esophagus 0.4-0.5% per year 5-10% lifetime

Current Management of Barrett’s Patients* Intestinal Metaplasia Surveillance (2-3 yrs) Low grade dysplasia Surveillance (6-12 mo) High grade dysplasia Surveillance (3 mo) vs. Esophagectomy This is how patients are managed right now - Watch and Wait Most patients are just watched As patient progresses to Low Grade Dysplasia, keep watching But once the dysplasia goes to High Grade, the choices have become very limited: Maybe Photodynamic Therapy or Esophagectomy Patients have to make a choice, They can be watched more often, or have the esophagus taken out. Then, if the diagnosis progresses to adenocarcinoma, the only choice is to take the esophagus out. Adenocarcinoma Esophagectomy vs. Palliative Care * May Differ per Institution

One Outcome of Surveillance Esophageal Adenocarcinoma Baseline Barrett’s Esophagus

Mixed Reflux of Gastric and Duodenal Juices is more Harmful to the Esophagus than Gastric Juice Alone Kauer WK et al Ann Surg 222: 525-533 Prevalence of esophageal bilirubin exposure

Bile Reflux Induces Adenocarcinoma of the Esophagus Ireland et al Ann Surg. 1996 September; 224(3): 358–371.

Antireflux Surgery 1976 Donahue and Bombeck defined a technique of "floppy" Nissen fundoplication (FNF) that prevented experimental pathologic reflux without preventing gaseous eructations or vomiting (normal reflux) when appropriate

LES Pressure Returns to Normal After Laparoscopic Fundoplication Peters JH et al. Ann Surg 1998;228:40-50.

24 Hour pH Studies after Laparoscopic Fundoplication Author # patients pH Negative Follow-up (months) Hinder (87%) 3-12 Hunter (91%) 12 Watson 3 Peters (93%) 21

Does Nissen reduce NonAcid Reflux? 8 patients with Barrett’s 24 hour pH and nonacid relfux - before (on omeprazole 20 mg BID) - after laparoscopic Nissen fundoplication

Acid Episodes Data are shown as median (horizontal line), interquartile range (box), and 5th to 95th percentile (vertical line)

P=0.001 Non-Acid Episodes Data are shown as median (horizontal line), interquartile range (box), and 5th to 95th percentile (vertical line)

Conclusions: Patients with Barrett’s esophagus Nissen eliminates acid and non-acid reflux PPI’s fail to eliminate acid reflux in 33-50% PPI’s do not reduce non-acid reflux

Ortiz et al Br J Surg. 1996 Feb;83(2):274-8 Conservative treatment versus antireflux surgery in Barrett's oesophagus: long-term results of a prospective study. Ortiz et al Br J Surg. 1996 Feb;83(2):274-8

Regression of Barrett’s after Fundoplication STUDY # PATIENTS short segment % REGRESSION U WASHINGTON Ann Surg. 2003 October; 238(4): 458–466 61 56% USC Ann Surg. 2001 October; 234(4): 532–539 26 14%

Should We Treat Barrett’s? Standard of care = removal of pre-cancerous lesions colon polyps (7 M annual U.S. colonoscopies) cervical dysplasia breast masses dermatologic lesions (moles, actinic keratoses) In the rest of the medical world, we take out pre-cancerous lesions. But for Barrett’s esophagus, what do we do? Just watch and wait.

Techniques for Mucosal Ablation Mechanical Endoscopic mucosal resection (EMR) Photochemical Photodynamic Therapy Thermal Argon plasma coagulation Multi-polar coagulation Bipolar energy Lasers: Argon, Nd: YAG, KTP-YAG Low-flow cryoablation Techniques for Mucosal Ablation The methods of mucosal ablation can be divided into three basic categories. The mechanical is endoscopic mucosal resection which can usually is applied with cautery. It involves making sessile lesions in the esophagus more polypoid through either injection of a bulking agent such as saline, methylcellulose, or hypertonic glucose or applying suction to the lesion. Thermal methods cauterize a mucosal lesions and can involve multiple types of thermal energy including laser therapy. Photodynamic therapy is a combination therapy in which a photosensitizing drug must be given first to allow its accumulation within the mucosa. The drug can then be activated by light which produces the photodynamic effect which causes cell death.

Overall Conclusions Balloon-based ablation can eliminate all histological evidence of IM after 1-2 treatments No safety issues LGD and HGD trials underway Promising early results Early data shows complete elimination of dysplasia after one treatment as possible

Conclusion This is an exciting, rapidly growing field. Currently, there is no ideal ablative modality. Patients should be treated with very close followup. Multimodal ablative therapy may have significant role.

Summary Barrett’s associated with Non Acid and Acid Reflux Non acid and acid reflux can cause esophageal cancer in experimental animals

Summary Nissen significantly reduces acid and non acid reflux PPI’s reduce acid reflux only and normalize 50-80% of patients

Summary There is no proof that Nissen fundoplication can prevent progression to cancer. But Nissen fundoplication is the only modality that can reduce both acid and non acid reflux and has been shown to reverse Short Segment Barrett’s