Safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett’s esophagus

Background and study aims: Endoscopic cryotherapy has been used successfully for the ablation of Barrett’s esophagus but outcome data are limited. The aim of this study was to assess the long-term safety and efficacy of carbon dioxide (CO₂) cryotherapy as primary or rescue treatment for Barrett’s esophagus with high grade dysplasia (HGD) or neoplasia.

Patients and methods: This was a retrospective, single-center, nonrandomized study carried out in an academic, tertiary care center and affiliated community hospital. A total of 78 patients with neoplastic Barrett’s esophagus who had not undergone previous ablation (treatment-naïve group) or who had persistent or recurrent neoplasia despite previous treatment (rescue treatment group) were enrolled. Visible Barrett’s lesions, when present, were removed by endoscopic mucosal resection, which was followed by CO₂ cryotherapy until neoplasia had been eradicated, or intervening therapy was necessary, or treatment was considered to have failed. Surveillance biopsies were obtained at standard intervals. Rates of complete response for cancer, HGD, and intestinal metaplasia were calculated. Treatment failure, recurrence, adverse events, progression, and mortality were also recorded.

Results: Between 2006 and 2013, 64 evaluable patients (20 treatment naïve, 44 rescue treatment) were treated and followed up (median time 4.2 years). At 1 year, the overall complete response rates were 77 % for cancer (10/13), 89 % for dysplasia 57/64), 94 % for HGD (60/64; 100 % for treatment naïve, 91 % for rescue treatment), and 55 % for intestinal metaplasia (35/64). Long-term complete response for neoplasia with rescue therapy was 87 % (56/64). Disease-specific mortality was 1/68 (2 %). Treatment failed to eradicate neoplasia in four patients (6 %) (all in the rescue group). Recurrent or new intestinal metaplasia was detected in 20/64 (31 %) after two negative follow-up procedures. Serious adverse events were noted in two patients (3 %). Post-cryotherapy pain occurred in four patients (6 %; only two needed analgesics). No bleeding or new strictures were noted. Buried Barrett’s was detected in 5/68 patients (7 %).

Conclusions: CO₂ cryotherapy was a safe and effective primary curative or rescue therapy for Barrett’s neoplasia.

• References

• 1 American GastroenterologicalAssociation, Spechler SJ, Sharma P et al. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology 2011; 140: 1084-1091
• 2 Wang KK, Sampliner RE. Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol 2008; 103: 788-797
• 3 Buttar NS, Wang KK, Lutzke LS et al. Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett’s esophagus. Gastrointest Endosc 2001; 54: 682-688
• 4 Kim HP, Bulsiewicz WJ, Cotton CC et al. Focal endoscopic mucosal resection before radiofrequency ablation is equally effective and safe compared with radiofrequency ablation alone for the eradication of Barrett’s esophagus with advanced neoplasia. Gastrointest Endosc 2012; 76: 733-739
• 5 Larghi A, Lightdale CJ, Ross AS et al. Long-term follow-up of complete Barrett’s eradication endoscopic mucosal resection (CBE-EMR) for the treatment of high grade dysplasia and intramucosal carcinoma. Endoscopy 2007; 39: 1086-1091
• 6 Okoro NI, Tomizawa Y, Dunagan KT et al. Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett’s esophagus. Clin Gastroenterol Hepatol 2012; 10: 150-154
• 7 Tomizawa Y, Iyer PG, Wong KeeSong LM et al. Safety of endoscopic mucosal resection for Barrett’s esophagus. Am J Gastroenterol 2013; 108: 1440-1447
• 8 Chung A, Bourke MJ, Hourigan LF et al. Complete Barretts excision by stepwise endoscopic resection in short-segment disease: long term outcomes and predictors of stricture. Endoscopy 2011; 43: 1025-1032
• 9 Lewis JJ, Rubenstein JH, Singal AG et al. Factors associated with esophageal stricture formation after endoscopic mucosal resection for neoplastic Barrett’s esophagus. Gastrointest Endosc 2011; 74: 753-760
• 10 Xue HB, Tan HH, Liu WZ et al. A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett’s esophagus. Endoscopy 2011; 43: 379-385
• 11 Canto MI, Gorospe EC, Shin EJ et al. Carbon dioxide (CO2) cryotherapy is a safe and effective treatment for Barrett’s esophagus with HGD/intramucosal carcinoma. Gastrointest Endosc 2009; 69: AB341
• 12 Spechler SJ, Sharma P, Souza RF et al. American Gastroenterological Association technical review on the management of Barrett’s esophagus. Gastroenterology 2011; 140: e18-52
• 13 Raju GS, Ahmed I, Xiao SY et al. Graded esophageal mucosal ablation with cryotherapy, and the protective effects of submucosal saline. Endoscopy 2005; 37: 523-526
• 14 Shin EJ, Amateau SK, Kim Y et al. Dose-dependent depth of tissue injury with carbon dioxide cryotherapy in porcine GI tract. Gastrointest Endosc 2012; 75: 1062-1067
• 15 Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002; 51: 130-131
• 16 Pasricha PJ, Hill S, Wadwa KS et al. Endoscopic cryotherapy: experimental results and first clinical use. Gastrointest Endosc 1999; 49: 627-631
• 17 Shaheen NJ, Sharma P, Overholt BF et al. Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 2009; 360: 2277-2288
• 18 Shaheen NJ, Overholt BF, Sampliner RE et al. Durability of radiofrequency ablation in Barrett’s esophagus with dysplasia. Gastroenterology 2011; 141: 460-468
• 19 Ell C, May A, Pech O et al. Curative endoscopic resection of early esophageal adenocarcinomas (Barrett’s cancer). Gastrointest Endosc 2007; 65: 3-10
• 20 Pech O, Bollschweiler E, Manner H et al. Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett’s esophagus at two high-volume centers. Ann Surg 2011; 254: 67-72
• 21 Bennett C, Vakil N, Bergman J et al. Consensus statements for management of Barrett’s dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process. Gastroenterology 2012; 143: 336-346
• 22 Phoa KN, van Vilsteren FG, Weusten BL et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA 2014; 311: 1209-1217
• 23 Phoa KN, Pouw RE, van Vilsteren FG et al. Remission of Barrett’s esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology 2013; 145: 96-104
• 24 Overholt BF, Wang KK, Burdick JS et al. Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett’s high-grade dysplasia. Gastrointest Endosc 2007; 66: 460-468
• 25 Pacifico RJ, Wang KK, Wongkeesong LM et al. Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett’s esophagus. Clin Gastroenterol Hepatol 2003; 1: 252-257
• 26 Greenwald BD, Dumot JA, Abrams JA et al. Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy. Gastrointest Endosc 2010; 71: 686-693
• 27 Gosain S, Mercer K, Twaddell WS et al. Liquid nitrogen spray cryotherapy in Barrett’s esophagus with high-grade dysplasia: long-term results. Gastrointest Endosc 2013; 78: 260-265
• 28 Shaheen NJ, Greenwald BD, Peery AF et al. Safety and efficacy of endoscopic spray cryotherapy for Barrett’s esophagus with high-grade dysplasia. Gastrointest Endosc 2010; 71: 680-685
• 29 Greenwald BD, Dumot JA, Horwhat JD et al. Safety, tolerability, and efficacy of endoscopic low-pressure liquid nitrogen spray cryotherapy in the esophagus. Dis Esophagus 2010; 23: 13-19
• 30 Pouw RE, Gondrie JJ, Sondermeijer CM et al. Eradication of Barrett esophagus with early neoplasia by radiofrequency ablation, with or without endoscopic resection. J Gastrointest Surg 2008; 12: 1627-1636
• 31 Manner H, May A, Miehlke S et al. Ablation of nonneoplastic Barretts mucosa using argon plasma coagulation with concomitant esomeprazole therapy (APBANEX): a prospective multicenter evaluation. Am J Gastroenterol 2006; 101: 1762-1769
• 32 Halsey KD, Chang JW, Waldt A et al. Recurrent disease following endoscopic ablation of Barrett’s high-grade dysplasia with spray cryotherapy. Endoscopy 2011; 43: 844-848
• 33 Vaccaro BJ, Gonzalez S, Poneros JM et al. Detection of intestinal metaplasia after successful eradication of Barrett’s esophagus with radiofrequency ablation. Dig Dis Sci 2011; 56: 1996-2000
• 34 Fleischer DE, Overholt BF, Sharma VK et al. Endoscopic radiofrequency ablation for Barrett’s esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy 2010; 42: 781-789
• 35 Krishnan K, Pandolfino JE, Kahrilas PJ et al. Increased risk for persistent intestinal metaplasia in patients with Barrett’s esophagus and uncontrolled reflux exposure before radiofrequency ablation. Gastroenterology 2012; 143: 576-581
• 36 Manner H, Rabenstein T, Pech O et al. Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs.surveillance (APE study). Endoscopy 2014; 46: 6-12
• 37 Korst RJ, Santana-Joseph S, Rutledge JR et al. Effect of hiatal hernia size and columnar segment length on the success of radiofrequency ablation for Barrett’s esophagus: a single-center, phase II clinical trial. J Thorac Cardiovasc Surg 2011; 142: 1168-1173
• 38 Goers TA, Leão P, Cassera MA et al. Concomitant endoscopic radiofrequency ablation and laparoscopic reflux operative results in more effective and efficient treatment of Barrett esophagus. J Am Coll Surg 2011; 213: 486-492
• 39 Sharma VK, Wang KK, Overholt BF et al. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc 2007; 65: 185-195
• 40 Simić A, Skrobić O, Micev M et al. Radiofrequency ablation for Barrett’s esophagus high-volume center initial results. Acta Chir Iugosl 2012; 59: 19-24
• 41 Dumot JA, Vargo JJ, Falk GW et al. An open-label, prospective trial of cryospray ablation for Barrett’s esophagus high-grade dysplasia and early esophageal cancer in high-risk patients. Gastrointest Endosc 2009; 70: 635-644
• 42 Vassiliou MC, von Renteln D, Wiener DC et al. Treatment of ultralong-segment Barrett’s using focal and balloon-based radiofrequency ablation. Surg Endosc 2010; 24: 786-791