Cryotherapy in the management of premalignant and malignant conditions of the esophagus

Table 1 Cryotherapy in Barrett’s esophagus

Author (yr)	No. of patients	Cryotherapy system used	Results of the study	Adverse events
Johnston et al[21] (2005)	11	Liquid nitrogen at -196 °C	100% CE-D and CE-IM	-
Canto et al[26] (2015)	44	Modified low-pressure CO2 cryotherapy system (Polar Wand, GI supply)	95.6% CE-D in LGD, 91.3% CE-D in HGD	4.5% (2) developed transient mild discomfort post-procedure.
Dumot et al[42] (2009)	30	LNSCT (CSA Medical Inc, Baltimore, Md)	68% CE-D in HGD, 80% CE-D in IMC	3.3% (1) developed perforation in a patient with known Marfan’s syndrome
Ghorbani et al[24] (2016)	96	LNSCT (2nd generation, CSA Medical, Baltimore, MD, United States)	91% CE-D in LGD, 81% CE-D in HGD, 61% CE-IM in LGD and 65% CE-IM in HGD respectively.	1% (1) developed stricture, which did not require dilation. 1% (1) hospitalized for bleeding in the setting of NSAID use
Ramay et al[44] (2017)	90 (50 for 3-yr analysis, 40 for 5-yr analysis)	LNSCT	3-yr analysis: 96% CE-D in HGD, 94% CE-D in LGD, 82% CE-IM; 5-yr analysis: 93% CE-D in HGD, 88% CE-D in LGD, 75% CE-IM	-

BE: Barrett’s esophagus; CE-D: Complete eradication of dysplasia; CE-IM: Complete eradication of intestinal metaplasia; HGD: High grade dysplasia; LGD: Low grade dysplasia; LNSCT: Liquid nitrogen spray cryotherapy; IMC: Intra-mucosal cancer.

Table 2 Cryotherapy in esophageal cancer

Author (yr)	No. of patients	Cryotherapy system used	Results	Adverse events
Cryotherapy in EAC
Greenwald et al[29] (2010)	79 (49 completed the treatment)	Low-pressure liquid nitrogen (< 5 psi) cryotherapy system	CE-D in 32%.	Benign strictures (12.6%), pain post treatment (25.3%)
Tsai et al[30] (2017)	88	Low-pressure liquid nitrogen (< 5 psi) cryotherapy system	CE of intraluminal disease in 76.3% T1a, 45.8% T1b, 66.2% T1, and 6.7% T2	Abdominal pain (19.3%), dysphagia (10.2%), sore throat (9%), and chest pain (8%)
Kachaamy et al[32] (2018)	49	Low-pressure liquid nitrogen system (CryoSpray Ablation System; CSA Medical, Inc, Lexington, Mass)	Improvement in mean dysphagia score	2% (1) developed a severe intra-procedural perforation, 2% (1) developed a benign stricture requiring dilation.
Cryotherapy in SCC
Cash et al[33] (2007)	1	Liquid nitrogen cryospray ablation	100% CE-D	Stricture development
Canto et al[34] (2018)	10	Nitrous oxide (CbFAS)	100% CE-D in LGIN, HGIN, SCC	Post-procedure pain (40%), esophageal stricture (20%)

EAC: Esophageal adenocarcinoma; CE-D: Complete eradication of dysplasia; CE: Complete eradication; CSA: Cryospray ablation; SCC: Squamous cell carcinoma; LGIN: Low-grade intraepithelial neoplasia; HGIN: High-grade intraepithelial neoplasia; CbFAS: Cryoballoon focal ablation system.

Table 3 Radiofrequency ablation vs cryotherapy

	Radiofrequency ablation	Cryotherapy
Mechanism of action	Bipolar electrode delivering radiofrequency energy to mucosa which generates heat and causes a uniform thermal injury on contact	Rapid freeze and thaw cycles cause immediate effects of slowing cellular metabolism and freezing intracellular water. Subsequently, ice formation results in disruption of cellular membranes and organelle dysfunction and eventually cellular apoptosis.
Maximal depth of injury	Mucosa (500-1000 microns)	Depends on the dose delivered; upto submucosa
Eradication of metaplasia	66.7%-100 %	41.3%-60% with cryospray; 84%-100% with cryoballoon
Eradication of dysplasia	87.5%-100%	78.8%-90% with cryospray; 92%-100% with cryoballoon
Post procedure pain requiring analgesics	4 d	2 d
Side effects	Esophageal strictures in 10.2%, bleeding 1.1%, perforation 0.2%	Esophageal strictures in 0%-12.5%, bleeding in 2 cases, perforation in 3 cases
Durability	CE-D 98% and CE-IM 91% at 3 yr	CE-D 92%, and CE-IM 81% at 5 yr (with cryospray only, cryoballoon data not available)
Recurrent metaplasia	16.10%	13.30%
Recurrent dysplasia	2.60%	3.60%
Recurrent high grade dysplasia or cancer	1.40%	1.30%

CE-D: Complete eradication of dysplasia; CE-IM: Complete eradication of intestinal metaplasia.