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Diseases of the Esophagus (2017) 30, 1–7
DOI: 10.1093/dote/dox087
Original Article
Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer
F. C. Tsai,1 S. Ghorbani,1 B. D. Greenwald,2 S. Jang,3 J. A. Dumot,3 M. J. McKinley,4 N. J. Shaheen,5
F. Habr,6 H. C. Wolfsen,7 J. A. Abrams,8 C. J. Lightdale,8 N. S. Nishioka,9 M. H. Johnston,10 A. Zfass,11
W. J. Coyle1
Scripps Clinic, La Jolla, California, University of Maryland School of Medicine and Greenebaum Cancer Center,
Baltimore, Maryland, Cleveland Clinic, Cleveland, Ohio, North Shore LIJ Health System and ProHEALTHcare
Associates, Syosset & Lake Success, New York, University of North Carolina School of Medicine, Chapel Hill,
North Carolina, Alpert School of Medicine of Brown University, Providence, Rhode Island, Mayo Clinic Jack8
sonville, Jacksonville, Florida, Columbia University Medical Center, New York, New York, Massachusetts Gen10
eral Hospital, Boston, Massachusetts, Lancaster Gastroenterology, Inc., Lancaster, Pennsylvania, and Virginia
Commonwealth University, Richmond, Virginia, USA
SUMMARY. Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries
significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy
of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or
were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry
and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy
was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76,
80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with
T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete
response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for
all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray
cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12.
This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for
early esophageal adenocarcinoma.
KEY WORDS: cryo, cryotherapy, endoscopic therapy, endoscopy, esophageal cancer.
Address correspondence to: Franklin Tsai, MD, Department of Gastroenterology, Scripps Clinic, 10666 N Torrey Pines Road, N203, La
Jolla, CA, 92037, USA. Email:
Specific author contributions:
Substantial contributions to conception and design of the work: Franklin C. Tsai, Shireen Ghorbani, Bruce D. Greenwald, Walter J. Coyle;
Acquisition, analysis and interpretation of data: Franklin C. Tsai, Shireen Ghorbani, Bruce D. Greenwald, Walter J. Coyle; Drafting work
and revising it critically for important intellectual content: Franklin C. Tsai, Shireen Ghorbani, Walter J. Coyle.
Final approval of version to be published: Franklin C. Tsai, Shireen Ghorbani, Bruce D. Greenwald, Sunguk Jang, John A. Dumot,
Matthew J. McKinley, Nicholas J. Shaheen, Fadlallah Habr, Herbert C. Wolfsen, Julian A. Abrams, Charles J. Lightdale, Norman S.
Nishioka, Mark H. Johnston, Alvin Zfass, Walter J. Coyle.
Agreement to be accountable for all aspects of the work related to accuracy or integrity: Franklin C. Tsai, Shireen Ghorbani, Bruce D.
Greenwald, Sunguk Jang, John A. Dumot, Matthew J. McKinley, Nicholas J. Shaheen, Fadlallah Habr, Herbert C. Wolfsen, Julian A.
Abrams, Charles J. Lightdale, Norman S. Nishioka, Mark H. Johnston, Alvin Zfass, Walter J. Coyle.
Revising work critically for important intellectual content: Bruce D. Greenwald, Sunguk Jang, John A. Dumot, Matthew J. McKinley,
Nicholas J. Shaheen, Fadlallah Habr, Herbert C. Wolfsen, Julian A. Abrams, Charles J. Lightdale, Norman S. Nishioka, Mark H.
Johnston, Alvin Zfass.
Substantial contributions to acquisition, analysis and interpretation of data: Sunguk Jang, John A. Dumot, Matthew J. McKinley,
Nicholas J. Shaheen, John A. Dumot, Matthew J. McKinley, Nicholas J. Shaheen, Fadlallah Habr, Herbert C. Wolfsen, Julian A. Abrams,
Charles J. Lightdale, Norman S. Nishioka, Mark H. Johnston, Alvin Zfass.
Financial disclosure: The authors have no financial disclosures to make. There were no conflicts of interest
C The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights
reserved. For permissions, please e-mail:
2 Diseases of the Esophagus
Adenocarcinoma of the esophagus is one of the
most rapidly increasing malignancies in the United
States.1,2 In 2017 it is estimated that there will be
16,940 new cases diagnosed and 15,690 deaths from
esophageal cancer.3 There has been a paradigm shift
in the treatment of superficial esophageal cancer. Surgical resection is less commonly performed for superficial malignancy while endoscopic techniques such
as endoscopic mucosal resection (EMR) and endoscopic ablation are increasingly performed.4–6 Alternative therapies for esophageal cancer are being developed.
Endoscopic spray cryotherapy of esophageal
mucosa using low pressure liquid nitrogen was first
described in 2007.7 Multiple studies have shown that
endoscopic spray cryotherapy of high grade dysplasia
is both efficacious and safe.8,9 The efficacy and safety
of liquid nitrogen spray cryotherapy for treatment of
esophageal cancer were demonstrated in more recent
studies.10,11 In a retrospective multicenter cohort of
patients with esophageal cancer treated with spray
cryotherapy, Greenwald et al. reported complete
intraluminal response in 61% of subjects including
75% complete response in those patients with T1a
disease who completed therapy.11 No severe adverse
events were reported.
The aim of this study is to assess the efficacy and
safety of spray cryotherapy in patients with adenocarcinoma of the esophagus.
Study design
This study includes patients enrolled retrospectively
and prospectively in an open-label registry and
patients in a retrospective cohort from 11 academic
and community practices. Patients were enrolled in
the registry between October 2008 and December
2011. All patients were treated with the CryoSpray
Ablation System (2nd generation, CSA Medical,
Baltimore, MD) using low-pressure liquid nitrogen.
Participating institutions included Cleveland Clinic,
University of Maryland, Mayo Clinic Jacksonville,
Virginia Commonwealth University, North Shore LIJ
Syosset Hospital, Columbia University, Lancaster
Gastroenterology, Massachusetts General Hospital,
Rhode Island Hospital, University of North Carolina, and Scripps Clinic, the latter of which served
as the data coordination site. The primary outcome
was complete eradication of local tumor confirmed by
biopsy. Additional outcomes included downgrade of
baseline disease and safety outcomes.
Patients at 11 institutions with biopsy proven
esophageal adenocarcinoma who were treated with
Fig. 1 Liquid nitrogen cryotherapy system.
spray cryotherapy with either curative or palliative
intent were included. The tumor stages were determined by endoscopic ultrasound, EMR, or surgery.
All patients had refused, failed, or were ineligible
for conventional therapies including esophagectomy,
chemotherapy, or radiotherapy. This study was
approved by the institutional review board at each
site. Informed consent was obtained for all patients,
except for retrospectively enrolled patients if informed
consent was waived by the institution’s IRB.
Patients were treated with endoscopic spray
cryotherapy, which consists of a console containing
a holding tank for medical grade liquid nitrogen
(−196◦ C) and uses a spray catheter to deliver low
pressure (<5 psi) cryogen with 25 W of energy to
the targeted tissue (Fig. 1). Patients were given either
moderate sedation with intravenous midazolam
combined with meperidine or fentanyl, or monitored
anesthesia care (MAC), based on physician discretion. A 16 Fr dual lumen modified decompression
tube was introduced through the mouth and passed
into the gastric antrum over a guidewire. This tube
provided both passive venting and active suction of
nitrogen gas to prevent gastric over distention. A
freeze-resistant disposable 7 Fr spray catheter was
passed through the working channel of a standard
Cryotherapy for esophageal cancer 3
Fig. 2 (A) Patient with esophageal adenocarcinoma (T1a by endoscopic ultrasound staging) not a candidate for surgery due to comorbidities or endoscopic mucosal resection due to inability to stop anticoagulation. (B) Spray cryotherapy of nodular lesion. (C) Appearance after
3 months with endoscopic biopsies negative for cancer or dysplasia.
endoscope, and liquid nitrogen was delivered to a
target site. Each site was typically treated with three
cycles of 20-second freezes; however freeze cycles
could be interrupted then resumed due to abdominal
distention or loss of visibility, and dosimetry could
be adjusted based on the endoscopist’s discretion.
The timer was initiated after the entire target area
was covered with white frost (Fig. 2). The abdomen
was continuously monitored for distention by a
trained assistant during treatment. Between each
cycle, the treated mucosa was allowed to fully thaw,
as evidenced by disappearance of the white frost.
Cryotherapy sessions were performed at 4 to 6 week
intervals until there was complete eradication of local
tumor confirmed by biopsies or when treatment was
halted due to lack of response, disease progression,
patient preference, or comorbid conditions. In some
cases, additional spray cryotherapy was performed
to eradicate residual intestinal metaplasia. Each site
had its own GI pathologists review the biopsy specimens. After completion of treatment, patients underwent surveillance endoscopies at intervals at the discretion of the home institution. Adverse events were
recorded at follow-up endoscopy sessions, periodic
clinic visits or by follow-up phone calls. Significant
adverse events (SAEs) were reported immediately and
defined as events associated with complete inability to
do work or usual activities, signs and symptoms that
were systemic in nature, or need for hospital admission
or intensive care.
Data analysis
For each subject, demographic information, baseline histology, tumor TNM staging, previous or
concurrent therapies, adverse events, number of
treatment sessions, results of cryotherapy, and final
disease type and stage were collected. For the safety
analysis, all patients and treatments were analyzed for
development of SAEs including severe pain (requiring
pain medication), stricture (either asymptomatic or
requiring dilation or intervention), and perforation.
For the intention to treat efficacy analysis, we included
patients who completed treatment based on eradication of local tumor or withdrawal for the abovementioned reasons. Complete response was defined as
complete eradication of all luminal cancer confirmed
by biopsies. Dropouts and deaths were included in
the efficacy analysis as treatment failures. Other concurrent therapies such as endoscopic mucosal resection (EMR), photodynamic therapy (PDT), argon
plasma coagulation (APC), and radiofrequency ablation (RFA) were allowed. But patients who underwent esophagectomy, chemotherapy, or radiation
after enrollment were considered treatment failures.
One hundred and four patients were screened among
the 11 participating institutions. Sixteen patients were
excluded due to missing T stages; therefore, eightyeight patients were enrolled in the study. Thirty
patients (34.1%) were enrolled in the open-label registry and 70 patients (79.5%) were enrolled in the
retrospective cohort, with 12 of the patients (13.6%)
enrolled in both. The median age was 76 years (range:
51–93, IQR 15) and 80.7% of patients were male.
Tumor length was reported in 81 patients, with a
mean length of 5.09 cm (range: 1–15 cm, SD 3.81).
Baseline tumor stages included 39 (44.3%) with T1a,
25 (28.4%) with T1b, 9 (10.2%) with unspecified T1,
and 15 (17%) with T2 (Table 1). At baseline, no
patients enrolled had known distant metastases (all
M0 or MX). Regional lymph node metastasis (N1)
was reported in no patients with T1a disease, 1 patient
(4%) with T1b disease, and five patients (33.3%) with
T2 disease.
Patients receiving treatment prior to enrollment
included 3 (3.4%) with prior esophagectomy, 14
(15.9%) with prior chemotherapy, 21 (23.9%) with
prior radiation therapy, 30 (34.1%) with EMR, 10
(11.4%) with PDT, 4 (4.5%) with APC, 3 (3.4%) with
RFA, and 1 (1.1%) with brachytherapy. Of the 14
patients who had previously received chemotherapy,
4 Diseases of the Esophagus
Table 1
Demographics and baseline characteristics
No. subjects
Table 2 Safety analysis
Total 88
therapy 86
71 (80.7)
17 (19.3)
76 (51–93, 15)
70 (81.4)
16 (18.6)
76 (51–93, 14)
(n = 88)
no. (%)
(n = 359)
no. (%)
0 (0.0)
17 (19.3)
10 (11.4)
17 (19.3)
12 (13.6)
9 (10.2)
8 (9)
7 (8)
3 (3.4)
3 (3.4)
2 (2.3)
1 (1.1)
1 (1.1)
0 (0.0)
0 (0.0)
0 (0.0)
Sex, no. (%)
Age, years, median
(range, IQR)
Ethnicity, no. (%)
African American
Not stated
Tumor stage, no. (%)
T1 (unspecified)
Tumor length, cm, mean
(range, SD)†
No. treatments, median
(range, IQR)
81 (92)
1 (1.1)
6 (6.8)
81 (94.2)
1 (1.2)
4 (4.6)
39 (44.3)
25 (28.4)
9 (10.2)
15 (17)
5.1 (1–15, 3.8)
38 (44.2)
24 (27.9)
9 (10.5)
15 (17.4)
5.1 (1–15, 3.8)
3 (1–25, 3)
3 (1–25, 3)
Treatment related
Cancer related
Unrelated to treatment/cancer
Abdominal Pain
Sore Throat
Chest Pain
GI bleed‡
17 (4.7)
12 (3.3)
16 (4.5)
17 (4.7)
16 (4.5)
4 (1.1)
3 (0.8)
4 (1.1)
2 (0.6)
1 (0.3)
0 (0.0)
0 (0.0)
† Three strictures were pre-existing prior to cryotherapy;
‡ Bleeding unrelated to cryotherapy, due to spontaneous
lesion in patient on supratherapeutic warfarin.
pts with no reported length.
IQR, interquartile range; SD, standard deviation.
Table 3 Treatment results (intention to treat analysis)
two had stage T1a disease but were not candidates for EMR or surgery due to co-morbidities
such as cirrhosis with esophageal varices. Twenty-nine
patients (33%) received concurrent therapy including
15 (17%) with EMR, 7 (8%) with APC, 4 (4.5%)
with RFA, 3 (3.4%) with radiation, 2 (2.3%) with
chemotherapy, 2 (2.3%) with esophageal stent, 1
(1.1%) with brachytherapy, and 6 (6.8%) patients
underwent esophagectomy after cryotherapy.
Safety analysis
A total of 359 cryotherapy treatments were performed
in these 88 patients. There were no cryotherapy-related
deaths or hospitalizations reported. There were a total
of 27 deaths (30.7%) including 17 (19.3%) cancerrelated deaths and 10 (11.4%) deaths from unrelated comorbidities (Table 2). There were 12 (13.6%)
patients that had esophageal strictures; however, three
of those patients had pre-existing strictures prior to
cryotherapy. There was one reported GI hemorrhage
due to a spontaneous bleeding lesion in the setting of
supratherapeutic warfarin unrelated to cryotherapy.
The most commonly reported postprocedure symptoms included abdominal pain (19.3%), dysphagia
(10.2%), sore throat (9%), and chest pain (8%).
Efficacy analysis
Eighty-six patients were included in the efficacy analysis, and the remaining two patients were still receiving
cryotherapy treatments at time of analysis. Patients
received a median of 3 cryotherapy treatments (range:
1–25, IQR 3). Forty-eight (55.8%) of patients had
By tumor stage
T1 total
Mucosal (T1a)
Submucosal (T1b)
Not stated
Complete response
no. (%)
Persistent tumor
no. (%)
48 (55.8)
38 (44.2)
47 (66.2)
29 (76.3)
11 (45.8)
7 (77.8)
1 (6.7)
24 (33.8)
9 (23.7)
13 (54.2)
2 (22.2)
14 (93.3)
complete response (eradication of all luminal tumor)
and 38 (44.2%) were nonresponders (Table 3). Complete responders underwent a median of 3 treatment
sessions (range: 1–13, IQR 2), compared to 4 for
nonresponders (range: 1–25, IQR 4). Mean followup was 18.4 months for all patients, and 23.5 months
for responders. At time of final follow-up, 44 patients
(51.2%) were alive and free of luminal disease, 3
(3.5%) were alive and free of disease postesophagectomy, 11 (13%) were alive with disease, 6 (7%) were
dead without disease, 4 (4.7%) were dead with disease,
and 18 (20.9%) were dead from disease. Final known
luminal histology at time of last follow-up was normal
in 29 patients (33.7%), nondysplastic Barrett’s in 10
(11.6%), low grade dysplasia in 4 (4.7%), high grade
dysplasia in 6 (7%), and adenocarcinoma in 37 (43%).
Response rates by baseline tumor stages are listed
in Table 3, including 76.3% response for T1a lesions,
45.8% for T1b lesions, 66.2% for all T1 lesions, and
6.7% for T2 lesions. There was no difference in median
age of responders versus nonresponders (75 years
versus 75.9 years, P = 0.68). Length of baseline disease was reported in 43/48 responders and 36/38 nonresponders. In those patients, there was no statistically
Cryotherapy for esophageal cancer 5
significant difference between mean length of baseline disease between responders versus nonresponders
(5 cm vs. 5.2 cm, P = 0.80). In a subgroup analysis
of the 29 patients with 2 cm or smaller tumors, the
response rates by baseline tumor stages were 62.1%
overall, 73.3% for T1a lesions, 42.9% for T1b lesions,
69.2% for all T1 lesions, and 0% for T2 lesions.
There were a total of 27 deaths during a mean
follow-up period of 18.4 months. For the 17 patients
who died of disease, the baseline disease stages were
T1a (1), T1b (8), and T2 (8). There were four patients
who died with disease from other causes (colon cancer,
myocardial infarction, pulmonary embolus, and renal
failure) and had baseline disease stages of T1a (1)
and T2 (3). There were six patients who died without
disease from unrelated causes (cardiac arrest, liver
failure, sepsis from leg wound, and three with unreported causes). The baseline disease stages for patients
who died without disease were T1a (3) and T1b (3).
The incidence of esophageal adenocarcinoma has
increased from 3.6 cases per million in 1973 to 25.6
cases per million in 2006 in the United States.4 Mortality has also increased, suggesting a need for alternative treatment options. Traditionally, esophagectomy had been the standard for treatment of early
esophageal adenocarcinoma; however there is a relatively high morbidity rate of 30%–50%.12–14 Advances
in surgical technique including minimally invasive
esophagectomy and improved perioperative care have
decreased operative mortality (3.8%) but is still associated with considerable morbidity of >40% regardless
of open versus minimally invasive approach.15
A preference for less invasive modalities has led
to the development and evaluation of endoscopic
therapy for the treatment of early esophageal carcinoma.16,17 The relatively low incidence of lymph node
metastasis in stage T1a esophageal adenocarcinoma
makes endoscopic therapy a feasible option.18 In addition, multiple studies have shown no difference in
survival and mortality rates between endoscopic and
surgical treatment of superficial esophageal adenocarcinoma, and a significantly higher rate of complications with surgery (32% vs. 0%).4,19,20 Endoscopic
therapy includes methods that ablate tissue, such as
cryotherapy, or those that resect tissue, such as endoscopic mucosal resection.21 Resection therapies have
the advantage of also providing histology for staging,
with studies showing that EMR changes initial staging
in more than 25% of cases.22,23
The use of endoscopic spray cryotherapy to treat
early esophageal malignancy was first reported in 2007
for the palliative treatment of recurrent esophageal
squamous cell carcinoma, which led to complete
remission for 24 months.7 More recently, endoscopic
spray cryotherapy has been shown to be a safe and
effective alternative to thermal ablative techniques
for treatment of early esophageal adenocarcinoma in
the appropriate patient population. Spray cryotherapy
has the benefit of not requiring tissue apposition in
order to be effective, which is useful in a tortuous
esophagus or other difficult anatomy, such as a large
hiatal hernia.24
In 2009, Dumot et al. reported on a single center,
prospective cohort of patients with BE and HGD
or T1a esophageal adenocarcinoma who underwent
cryotherapy with a median follow-up of 1 year.10 Elimination of cancer and intestinal metaplasia was seen
in 80% of patients with T1a esophageal adenocarcinoma. Three of 6 patients with complete response had
recurrence of dysplasia or cancer in the gastric cardia.
In a 2010 multicenter, retrospective cohort, 79 patients
with esophageal adenocarcinoma (94%) or squamous
cell carcinoma who were not considered surgical candidates or who refused esophagectomy were treated
with spray cryotherapy.11 Of the 49 patients who completed therapy, complete response of intraluminal disease was seen in 72% of all T1 tumors and 75% of all
T1a tumors. No serious adverse events were reported
and mean follow-up was 10.8 months.
For patients who have visible or nodular lesions in
the setting of BE, EMR or ESD is preferred as the
first step in endoscopic treatment, which will provide
pathologic staging.22 In our registry, EMR was not
possible in all cases due to inability to stop anticoagulation, scarring from previous treatment, T1b or
higher lesion, or inability to visualize the cancer endoscopically, necessitating ablation of the entire segment of BE. When these patients were treated, ESD
was not widely available in the United States and
widespread adoption continues to be slow. However,
studies show that ESD is an effective and safe option
and may be considered for patients with superficial
esophageal cancer at institutions with expertise in this
In our study, data was pooled from 11 academic
and community practices in an open-label registry
and retrospective cohort. Eighty-eight subjects with
esophageal adenocarcinoma carcinoma who were
not surgical candidates or otherwise had failed or
refused conventional therapies underwent endoscopic
spray cryotherapy using low-pressure liquid nitrogen.
Complete eradication of tumor was seen in 76.3%
of T1a lesions and 45.8% of T1b lesions with no
deaths or severe adverse events directly related to
cryotherapy. This suggests that earlier stage appears
to predict response of esophageal cancer to spray
cryotherapy. There were 12 patients that had strictures, however three of the 12 patients had pre-existing
The strengths of this study include participation of
a large number of patients from both academic and
community centers, and few exclusion criteria thereby
6 Diseases of the Esophagus
better representing those patients encountered in clinical practice. Because most of these patients had failed
or were not candidates for conventional therapy, they
represent a more challenging cohort of patients to
achieve therapeutic success. The main limitation of
this study was lack of standardization of treatment
across the different centers. We were unable to control for possible variability in technique, dosimetry,
and clinical decision making of the investigators at the
different sites, issues inherent to all registry studies.
This study pooled data from a prospective registry
with a retrospective cohort. Additionally, there were
16 patients excluded from the study due to missing T
stage. It cannot be determined with certainty if the
patients with missing data could have affected the
results either positively or negatively. T staging was
obtained by pathology in 37.5% of patients but was
obtained by EUS for the rest of the patients, including
56% of those with T1a and 44% with T1b disease.
Because T1a and T1b disease may be difficult to accurately stage by EUS, it is possible that there was under
or over staging. Furthermore, this study was unable to
discern intent of treatment as palliative versus curative
for each patient, therefore the interpretation of outcomes was conservative, in that a palliative ‘success’
such as alleviation of dysphagia, might still be viewed
as a failure in our analysis if there was residual intraluminal disease.
It should also be noted that all patients in this
study were treated prior to September 2012 using
the 2nd generation CryoSpray Ablation System (CSA
Medical) which was in clinical use from 2007 to
2013 and has now been replaced by the 3rd generation TruFreeze System (CSA Medical) with several advancements including spray catheter flexibility
and more laminar flow of liquid nitrogen. Therefore, the results from this study may not be applicable to the current device in clinical use. Whether the
technological advancements of the current generation
cryotherapy device will result in improvements in efficacy and safety is an area of ongoing research.
This study suggests that endoscopic spray
cryotherapy is safe, well tolerated, and efficacious for
treatment of early esophageal adenocarcinoma, either
as an adjunct or alternative to conventional therapy
depending on the clinical situation. Additional studies
are needed to evaluate the long-term durability of
The administration costs for the registry were partially funded by CSA Medical. Participating investigators include Dr. James S. Barthel, Dr. Amit Bhatt,
and Dr. Rohit Makkar for their contributions to the
study including collection of data and providing care
for study patients.
1 Hur C, Miller M, Kong C Y et al. Trends in esophageal
adenocarcinoma incidence and mortality. Cancer 2013;
119: 1149–58.
2 Pohl H, Sirovich B, Welch H G. Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol
Biomarkers Prev 2010; 19: 1468–70.
3 American Cancer Society. Cancer Facts and Figures 2017.
Atlanta, GA: American Cancer Society, 2017.
4 Ngamruengphong S, Wolfsen H C, Wallace M B. Survival of
patients with superficial esophageal adenocarcinoma after endoscopic treatment vs. surgery. Clin Gastroenterol Hepatol 2013;
11: 1424–9.
5 Wani S, Drahos J, Cook M B et al. Comparison of endoscopic
therapies and surgical resection in patients with early esophageal
cancer: a population-based study. Gastrointest Endosc 2014;
79: 224–32.
6 DeMeester S R. Evaluation and treatment of superficial
esophageal cancer. J Gastrointest Surg 2010; 14(Suppl 1): S94–
7 Cash B D, Johnston LR, Johnston M H. Cryospray ablation
(CSA) in the palliative treatment of squamous cell carcinoma
of the esophagus. World J Surg Oncol 2007; 5: 34.
8 Shaheen N J, Greenwald B D, Peery A F et al. Safety and
efficacy of endoscopic spray cryotherapy for Barrett’s esophagus with high-grade dysplasia. Gastrointest Endosc 2010;
71: 680–5.
9 Ghorbani S, Tsai F C, Greenwald B D et al. Safety and efficacy of endoscopic spray cryotherapy for Barrett’s dysplasia:
results of the National Cryospray Registry. Dis Esophagus 2016;
29: 241–7.
10 Dumot J A, Vargo J J, Falk G W, Frey L, Lopez R, Rice T W. 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: 635–44.
11 Greenwald B D, Dumot J A, Abrams J A et al. Endoscopic spray
cryotherapy for esophageal cancer: safety and efficacy. Gastrointest Endosc 2010; 71: 686–93.
12 Stein H J, Feith M, Bruecher B L, Naehrig J, Sarbia M, Siewert
J R. Early esophageal squamous cell and adenocarcinoma: pattern of lymphatic spread and prognostic factors for long term
survival after surgical resection. Ann Surg 2005; 242: 566–73.
13 Rice T W, Blackstone E H, Goldblum J R et al. Superficial adenocarcinoma of the esophagus. J Thorac Cardiovasc Surg 2001;
122: 1077–90.
14 Prasad G A, Wu T T, Wigle D A et al. Endoscopic and surgical
treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett’s esophagus. Gastroenterology 2009; 137: 815–23.
15 Yibulayin W, Abulizi S, Lv H, Sun W. Minimally invasive
oesophagectomy versus open esophagectomy for resectable
esophageal cancer: a meta-analysis. World J Surg Oncol 2016;
14: 304.
16 Leggett C L, Gorospe E C, Wang K W. Endoscopic therapy of
Barrett’s esophagus and early esophageal adenocarcinoma. Gastroenterol Clin North Am 2013; 42: 175–85.
17 Chennat J, Waxman I. Endoscopic treatment of Barrett’s esophagus: From metaplasia to intramucosal carcinoma. World J Gastroenterol 2010; 16: 3780–5.
18 Pech O, May A, Manner H et al. Long-term efficacy and safety
of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 2014; 146: 652–60.
19 Pech O, Bollschweiler E, Manner H, Leers J, Ell C, Hölscher
A H. 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.
20 Zehetner J, DeMeester S R, Hagen J A et al. Endoscopic resection and ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma. J Thorac Cardiovasc
Surg 2011; 141: 39–47.
21 Davila M L, Hofstetter W L. Endoscopic management of
Barrett’s esophagus with high-grade dysplasia and early-stage
esophageal adenocarcinoma. Thorac Surg Clin 2013; 23: 479–
22 Moss A, Bourke M J, Hourigan L F et al. Endoscopic resection
for Barrett’s high-grade dysplasia and early esophageal
adenocarcinoma: an essential staging procedure with
Cryotherapy for esophageal cancer 7
long-term therapeutic benefit. Am J Gastroenterol 2010;
105: 1276–83.
23 Peters F P, Brakenhoff K P, Curvers W L et al. Histologic
evaluation of resection specimens obtained at 293 endoscopic
resections in Barrett’s esophagus. Gastrointest Endosc 2008; 67:
24 Shaheen N J. Cryotherapy for the eradication of Barrett esophagus or early cancer. Gastroenterol Hepatol 2012; 8: 758–60.
25 Sun F, Yuan P, Chen T, Hu J. Efficacy and complication of endoscopic submucosal dissection for
review and meta-analysis. J Cardiothorac Surg 2014;
9: 78.
26 Bhatt A, Abe S, Kumaravel A, Vargo J, Saito Y. Indications and
techniques for endoscopic submucosal dissection. Am J Gastroenterol 2015; 110: 784–91.
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