The incidence of esophageal cancer, in particular esophageal adenocarcinoma, is increasing, largely due to an increase in risk factors for adenocarcinoma. When esophageal cancer is confirmed by upper endoscopy, staging is required for the optimal selection of patients who should undergo esophageal resection. Neoadjuvant chemoradiation may be able to improve survival after esophageal cancer surgery. Endoscopic therapy for early esophageal neoplasia is effective and safe, with the best results being obtained by an individualized approach using endoscopic mucosal resection, ablative therapy, or both. Finally, dysphagia from esophageal cancer can be successfully treated with stent placement or single-dose brachytherapy. Future research should establish whether combinations of chemotherapy with or without radiation therapy play a role in survival.
Esophageal cancer is diagnosed in about 400,000 patients per year, which makes it the ninth most common malignancy worldwide and sixth on the list of cancer mortality causes. It is important to realize that it is somewhat difficult to determine its true incidence because cancer in the distal esophagus, particularly around the gastroesophageal (GE) junction, may be classified as esophageal cancer or as gastric cardia cancer.
For the purpose of this review, esophageal squamous cell carcinoma (ESCC) is defined as a tumor in the squamous epithelium that lines the normal esophagus. Adenocarcinomas are tumors that are located at the interface of the distal esophagus and proximal stomach and are subdivided into esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma. EAC usually develops in Barrett’s esophagus (BE) (Siewert type I). Gastric cardia adenocarcinomas are tumors that arise in the cardia (Siewert type II) or subcardia (Siewert type III). Siewert type II and III tumors often extend proximally across the GE junction, causing dysphagia. In this review, predominantly ESCC and EAC are considered.
The prognosis of esophageal cancer has slightly improved over the last few years in patients eligible to undergo a surgical resection; however, the 5-year survival rate in the resected group is still not higher than 30% to 35%. For all patients who have esophageal cancer, the 5-year survival rate does not exceed 20%. Early detection and treatment offers the best chance for cure.
This article reviews the epidemiology and pathogenesis of esophageal cancer. In addition, endoscopic diagnosis and staging methods of esophageal cancer are discussed. Curative treatment options for esophageal cancer (early esophageal neoplasia and advanced esophageal cancer) are reviewed. Finally, the most frequently used palliative methods for incurable esophageal cancer are summarized.
Epidemiology
The incidence of esophageal cancer is high in Western Europe, south-central Asia, eastern Africa, and parts of South America. In the Western world, the incidence is highest in the United Kingdom, France, Ireland, and the United States, with a higher incidence in men than in women, particularly in France and Slovakia.
There has been a large increase of EAC in so-called “developed countries” and a modest decrease of ESCC. Rates of EAC have been increasing in the United States, the United Kingdom, Scandinavia, France, Switzerland, Denmark, Italy, Slovakia, the Netherlands (restricted to men), Australia, and New Zealand.
This increase in rates of EAC may be partly due to a diagnostic shift. Tumors arising around the GE junction used to be classified as cardia adenocarcinomas; therefore, an increase in EAC could appear if tumors at or near the GE junction are increasingly being identified as esophageal in origin. Cardia adenocarcinoma rates, however, would then diminish to a similar extent, which has not occurred. Rates may also increase with an earlier endoscopy-based diagnosis, but the stage distribution has not changed over time, and survival consistently has been poor, even for patients diagnosed with localized disease.
The increase in incidence of EAC could also be real. A cohort study using a large general practice database in the Netherlands showed that the incidence of EAC increased from 1.7 in 100,000 (95% confidence interval [CI], 0.3–5.4) in 1997 to 6.0 in 100,000 (95% CI, 3.3–10.2) in 2002 ( R 2 = 0.87). Similarly, the incidence of BE, the main precursor of EAC, increased from 14.3 in 100,000 (95% CI, 8.6–22.4) in 1997 to 23.1 in 100,000 (95% CI, 17.2–30.6) in 2002 ( R 2 = 0.87). The increase in the incidences of EAC and BE was independent of the number of upper endoscopies performed, because this number decreased from 7.2 in 1000 (95% CI, 6.7–7.7) to 5.7 in 1000 (95% CI, 5.4–6.1) in the same time period.
These observations suggest that the increase of EAC is real and may reflect changes in the prevalence of risk factors. It is interesting to note that the mortality from esophageal cancer shows the same patterns. Due to the increased incidence and the limited improvement in survival of patients who have esophageal cancer, mortality rates have been increasing in most countries.
Pathogenesis
The question regarding which individuals are at highest risk of developing esophageal cancer is important because it may help to identify those at highest risk of developing this malignancy.
Exogenous Factors
In the 1990s, two milestone articles on this topic were published. In 1995, Vaughan and colleagues published a case-control study of risk factors for esophageal cancer that was conducted among residents of western Washington. Information on body mass index (BMI), cigarette use, alcohol intake, and other risk factors was collected from 404 cases or their next of kin (including 298 EAC cases and 106 ESCC cases) and 724 control subjects. Together, the risk factors of obesity, cigarette smoking, and alcohol use accounted for approximately 50% of all EAC cases diagnosed over that period. In comparison, cigarette smoking and alcohol intake alone accounted for 87% of all ESCC cases.
In 1999, Lagergren and colleagues published a case-control study from Sweden. Information on the history of GE reflux was collected from 189 patients who had EAC and 262 who had cardia adenocarcinoma in the period 1995 to 1997. For comparison, 820 control subjects and 167 patients who had ESCC were interviewed. Among persons who had recurrent symptoms of reflux, odds ratios (ORs) were 7.7 (95% CI, 5.3–11.4) for EAC and 2.0 (95% CI, 1.4–2.9) for cardia adenocarcinoma. The more frequent, more severe, and longer-lasting the reflux symptoms, the greater the risk. Among persons who had long-standing and severe symptoms of reflux, ORs were 43.5 (95% CI, 18.3–103.5) for EAC and 4.4 (95% CI, 1.7–11.0) for cardia adenocarcinoma. The risk of ESCC was not associated with reflux (OR, 1.1; 95% CI, 0.7–1.9).
BE is a recognized risk factor for EAC that has a 30 to 50 fold increased risk of developing this malignancy. It is not well known, however, which patients who have BE have the highest risk of malignant progression. The evidence suggests that significant risk factors for EAC in BE are male sex, Caucasian race, and GE reflux disease (GERD). Further details on BE are discussed in the article by Bird-Lieberman and colleagues found elsewhere in this issue.
De Jonge and colleagues performed a case-control study to determine additional risk factors for EAC in BE. They included 91 cases of EAC and 244 control subjects who had BE. Information on demographic, anthropometric, and lifestyle characteristics; family history; symptoms of GERD; and medication use was collected by a questionnaire. Cases more often were current smokers (OR, 3.7; 95% CI, 1.4–9.9), had a BMI greater than 25 assessed at age 20 years (OR, 2.6; 95% CI, 1.2–5.5), and more frequently had been working in a stooped posture at age 20 years (OR, 2.0; 95% CI, 1.1–3.9). In addition, cases experienced fewer symptoms of heartburn (OR, 0.3; CI, 0.2–0.5) and less frequently used proton pump inhibitors (OR, 0.1; CI, 0.05–0.2). These data confirmed that the risk of EAC in BE is related to risk factors for GERD.
BMI is a clearly a risk factor for EAC, but its distribution does not reflect the demographic distribution of this cancer (which is highest among white men). Corley and colleagues thus performed a case-control study with 206,974 members of the Kaiser Permanente Health Checkup cohort, whereby subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of EACs and cardia adenocarcinomas using registry data. In total, 101 cases of EAC, 105 of cardia adenocarcinoma, and 144 of ESCC were detected. Increasing abdominal diameter (25 cm versus <20 cm) was strongly associated with an increased risk of EAC (OR, 3.5; 95% CI, 1.3–9.3). Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.8; 95% CI, 1.1–20.1). The association was also not diminished by adjustment for GERD-type symptoms, although reflux-type symptoms were separately associated with abdominal diameter and with cancer risk. Abdominal diameter (25 cm versus <20 cm) was not associated with the risk of cardia adenocarcinoma (OR, 1.3; 95% CI, 0.4–4.2) or ESCC (OR, 0.8; 95% CI, 0.3–1.9).
It can be concluded that ESCC is predominantly associated with alcohol use and smoking. To a lesser extent, the same risk factors apply for EAC, but in addition, GERD and BE and their common risk factor abdominal obesity contribute to this malignancy. Because abdominal obesity is more common among men, this suggests that an increase in obesity may disproportionately increase EAC risk in men.
Endogenous Factors
Another way of understanding pathogenetic mechanisms of esophageal cancer is to identify gene expression profiles. Gene expression profiles (DNA microarray) in biopsy specimens from 17 patients who had BE and EAC showed many genes and patterns not previously identified in addition to genes that were demonstrated to be overexpressed by other epithelial cancers, suggesting mutual mechanisms in pathogenesis. In addition, a similar stromal gene expression profile between BE and EAC was found, indicating that stromal and extracellular matrix genes associated with tumor growth are expressed long before pathologic evidence of dysplasia is present. Finally, no differences between short-segment BE (SSBE; BE length <2 cm) and long-segment BE (LSBE; BE length ≥2 cm) were found, which suggests that differences in cell type or cell physiology are not responsible for the suggested higher risk of EAC in LSBE. These results provide important data for analysis of specific genes and pathways related to carcinogenesis of the esophagus. Thus, in combination with the previously mentioned exogenous risk factors, these types of genetic analyses improve our understanding of the main pathogenetic mechanisms of esophageal cancer.
Pathogenesis
The question regarding which individuals are at highest risk of developing esophageal cancer is important because it may help to identify those at highest risk of developing this malignancy.
Exogenous Factors
In the 1990s, two milestone articles on this topic were published. In 1995, Vaughan and colleagues published a case-control study of risk factors for esophageal cancer that was conducted among residents of western Washington. Information on body mass index (BMI), cigarette use, alcohol intake, and other risk factors was collected from 404 cases or their next of kin (including 298 EAC cases and 106 ESCC cases) and 724 control subjects. Together, the risk factors of obesity, cigarette smoking, and alcohol use accounted for approximately 50% of all EAC cases diagnosed over that period. In comparison, cigarette smoking and alcohol intake alone accounted for 87% of all ESCC cases.
In 1999, Lagergren and colleagues published a case-control study from Sweden. Information on the history of GE reflux was collected from 189 patients who had EAC and 262 who had cardia adenocarcinoma in the period 1995 to 1997. For comparison, 820 control subjects and 167 patients who had ESCC were interviewed. Among persons who had recurrent symptoms of reflux, odds ratios (ORs) were 7.7 (95% CI, 5.3–11.4) for EAC and 2.0 (95% CI, 1.4–2.9) for cardia adenocarcinoma. The more frequent, more severe, and longer-lasting the reflux symptoms, the greater the risk. Among persons who had long-standing and severe symptoms of reflux, ORs were 43.5 (95% CI, 18.3–103.5) for EAC and 4.4 (95% CI, 1.7–11.0) for cardia adenocarcinoma. The risk of ESCC was not associated with reflux (OR, 1.1; 95% CI, 0.7–1.9).
BE is a recognized risk factor for EAC that has a 30 to 50 fold increased risk of developing this malignancy. It is not well known, however, which patients who have BE have the highest risk of malignant progression. The evidence suggests that significant risk factors for EAC in BE are male sex, Caucasian race, and GE reflux disease (GERD). Further details on BE are discussed in the article by Bird-Lieberman and colleagues found elsewhere in this issue.
De Jonge and colleagues performed a case-control study to determine additional risk factors for EAC in BE. They included 91 cases of EAC and 244 control subjects who had BE. Information on demographic, anthropometric, and lifestyle characteristics; family history; symptoms of GERD; and medication use was collected by a questionnaire. Cases more often were current smokers (OR, 3.7; 95% CI, 1.4–9.9), had a BMI greater than 25 assessed at age 20 years (OR, 2.6; 95% CI, 1.2–5.5), and more frequently had been working in a stooped posture at age 20 years (OR, 2.0; 95% CI, 1.1–3.9). In addition, cases experienced fewer symptoms of heartburn (OR, 0.3; CI, 0.2–0.5) and less frequently used proton pump inhibitors (OR, 0.1; CI, 0.05–0.2). These data confirmed that the risk of EAC in BE is related to risk factors for GERD.
BMI is a clearly a risk factor for EAC, but its distribution does not reflect the demographic distribution of this cancer (which is highest among white men). Corley and colleagues thus performed a case-control study with 206,974 members of the Kaiser Permanente Health Checkup cohort, whereby subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of EACs and cardia adenocarcinomas using registry data. In total, 101 cases of EAC, 105 of cardia adenocarcinoma, and 144 of ESCC were detected. Increasing abdominal diameter (25 cm versus <20 cm) was strongly associated with an increased risk of EAC (OR, 3.5; 95% CI, 1.3–9.3). Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.8; 95% CI, 1.1–20.1). The association was also not diminished by adjustment for GERD-type symptoms, although reflux-type symptoms were separately associated with abdominal diameter and with cancer risk. Abdominal diameter (25 cm versus <20 cm) was not associated with the risk of cardia adenocarcinoma (OR, 1.3; 95% CI, 0.4–4.2) or ESCC (OR, 0.8; 95% CI, 0.3–1.9).
It can be concluded that ESCC is predominantly associated with alcohol use and smoking. To a lesser extent, the same risk factors apply for EAC, but in addition, GERD and BE and their common risk factor abdominal obesity contribute to this malignancy. Because abdominal obesity is more common among men, this suggests that an increase in obesity may disproportionately increase EAC risk in men.
Endogenous Factors
Another way of understanding pathogenetic mechanisms of esophageal cancer is to identify gene expression profiles. Gene expression profiles (DNA microarray) in biopsy specimens from 17 patients who had BE and EAC showed many genes and patterns not previously identified in addition to genes that were demonstrated to be overexpressed by other epithelial cancers, suggesting mutual mechanisms in pathogenesis. In addition, a similar stromal gene expression profile between BE and EAC was found, indicating that stromal and extracellular matrix genes associated with tumor growth are expressed long before pathologic evidence of dysplasia is present. Finally, no differences between short-segment BE (SSBE; BE length <2 cm) and long-segment BE (LSBE; BE length ≥2 cm) were found, which suggests that differences in cell type or cell physiology are not responsible for the suggested higher risk of EAC in LSBE. These results provide important data for analysis of specific genes and pathways related to carcinogenesis of the esophagus. Thus, in combination with the previously mentioned exogenous risk factors, these types of genetic analyses improve our understanding of the main pathogenetic mechanisms of esophageal cancer.
Diagnosis
Upper endoscopy is the preferred investigation for patients in whom there is a suspicion of esophageal cancer. Advances in endoscopic imaging such as narrow band imaging—and endocytoscopy and confocal endomicroscopy for even more detailed mucosal information—hold the promise that they may be able to better detect early malignant lesions of the esophagus. Further details on these new endoscopic imaging techniques are discussed in the article by Reddymasu and Sharma found elsewhere in this issue.
More advanced esophageal cancers can be exophytic, stenotic, or ulcerative or show a combination of these features ( Fig. 1 ). Stenotic lesions are often circular and may prevent passage of a standard endoscope (diameter 9–11 mm). Because it is important to determine the upper and lower limit of the lesion and to visualize the stomach, which may be used for reconstructive purposes following esophagectomy, one should consider using a small-caliber endoscope (diameter 4.5–6 mm) in these cases. Another option is to dilate a stenotic tumor, which can safely be done by performing serial, progressive dilations over several days rather than by performing a single dilation. Following endoscopy of a dilated stenotic tumor, it is also advisable to perform endoscopic ultrasound (EUS) during the same session. Dilation of stenotic tumors significantly influences the accuracy of EUS staging in advanced tumors. Endoscopic biopsy completes an endoscopic examination of a suspected tumor. Without histologic proof, a strong suspicion may exist but the diagnosis cannot be established. At least six biopsy samples should be taken, preferably from the center and from the edges of the tumor.
Staging
To optimize the selection of patients who have esophageal cancer for curative or palliative treatment, it is important to determine the depth of infiltration of the tumor into the esophageal wall (T stage) and the presence of malignant regional lymph nodes (N stage) and distant metastases (M stage). An algorithm that can be used to stage esophageal cancer is summarized in Fig. 2 .
EUS is nowadays used to determine the depth of tumor invasion and the presence of malignant regional and celiac lymph nodes in patients who have esophageal cancer. CT and fludeoxyglucose F18 positron emission tomography (FDG-PET) are commonly applied to determine whether malignant lymph nodes or distant metastases are present.
A recent meta-analysis evaluated the use of EUS for the detection of malignant regional and celiac lymph nodes, the use of CT for the detection of malignant regional and abdominal lymph nodes and distant metastases, and the use of FDG-PET for the detection of malignant regional lymph nodes and distant metastases. Random-effects pooled sensitivities of EUS, CT, and FDG-PET for regional lymph node metastases were 0.80 (95% CI, 0.75–0.84), 0.50 (95% CI, 0.41–0.60), and 0.57 (95% CI, 0.43–0.70), respectively; specificities were 0.70 (95% CI, 0.65–0.75), 0.83 (95% CI, 0.77–0.89), and 0.85 (95% CI, 0.76–0.95), respectively. Diagnostic performance was not different across these tests. For detection of celiac lymph node metastases by EUS ( Fig. 3 ), sensitivity and specificity were 0.85 (95% CI, 0.72–0.99) and 0.96 (95% CI, 0.92–1.00), respectively. For abdominal lymph node metastases by CT, these values were 0.42 (95% CI, 0.29–0.54) and 0.93 (95% CI, 0.86–1.00), respectively. For distant metastases, sensitivity and specificity were 0.91 (95% CI, 0.86–0.96) and 0.52 (95% CI, 0.33–0.71) for CT, and 0.71 (95% CI, 0.62–0.79) and 0.93 (95% CI, 0.89–0.97) for FDG-PET, respectively. Compared with CT, diagnostic performance of FDG-PET for distant metastases was significantly higher and was not affected by study and patient characteristics.
EUS, CT, and FDG-PET each play a distinctive role in the detection of metastases in esophageal cancer patients. For the detection of regional and celiac lymph node metastases, EUS is most sensitive, whereas CT and FDG-PET are more specific tests. For the evaluation of distant metastases, FDG-PET may have a higher sensitivity than CT. The combined use of FDG-PET and CT, which is increasingly being applied, could be of clinical value, with FDG-PET detecting possible metastases and CT confirming or excluding their presence and precisely determining their location.
Fludeoxyglucose F18 Positron Emission Tomography
The role of FDG-PET in a state-of-the-art preoperative staging protocol including CT of the chest and upper abdomen, EUS, and ultrasonography of the neck, combined with selective fine-needle aspiration if indicated, is questioned by some investigators. To determine the role of FDG-PET in staging of esophageal cancer, 199 patients considered eligible for curative surgery after CT, EUS, and ultrasonography of the neck underwent FDG-PET in a prospective cohort study. FDG-PET revealed suspicious hot spots in 30 of 199 (15%) patients. Metastases were confirmed in 8 (4%). In 6 of these, distant metastases were confirmed before surgery, but exploratory surgery was necessary for histologic confirmation in the other 2. All 8 upstaged patients already had clinical stage III to IV disease before FDG-PET (7% of 122 with stage III–IV disease). In another 7 (4%) patients, hot spots appeared to be synchronous neoplasms (mainly colonic polyps). Those in the remaining 15 (8%), however, were false positive, leading to unnecessary additional investigations.
FDG-PET may thus improve the selection of patients who have esophageal cancer for potentially curative surgery, especially when in stages III to IV. The diagnostic benefit, however, seems limited to after state-of-the-art staging procedures.
CT
Recently, it was suggested that metastases in patients who have esophageal cancer were more frequently detected on CT examinations in a high-volume referral center for esophageal cancer. Thus, two radiologists from referral centers (“expert radiologists”) and six radiologists from nonreferral centers (“nonexpert radiologists”) evaluated 72 hard-copy CT examinations of patients diagnosed with esophageal or cardia cancer between 1994 and 2003. Compared with nonexpert radiologists, expert radiologists almost three times more frequently (OR, 2.9; 95% CI, 1.4–6.3) made a correct diagnosis of the presence or absence of distant metastases. For the subgroup of CT examinations showing distant metastases, a statistically significant correlation (OR, 3.5; 95% CI, 1.4–9.1) was found between CT quality and a correct diagnosis.
It therefore appears that radiologist experience and quality of the CT examination play a role in the detection of distant metastases in esophageal or gastric cardia cancer. This finding could lead to the suggestion that staging procedures for esophageal and gastric cardia cancer should preferably be performed in centers with state-of-the-art equipment and experienced radiologists.
Endoscopic Ultrasonography
Is the same also true of EUS? It is known that a learning curve exists for the quality of performing EUS. After having performed 75 to 100 examinations, acceptable results can be obtained; however, it is not known whether the number of EUS investigations in subsequent years affects the results of esophageal cancer staging over time. Van Vliet and colleagues compared the results of EUS in the evaluation of T stage and the presence of regional and celiac lymph nodes in (1) a low-volume center where fewer than 50 EUS procedures per endoscopist per year were performed with (2) seven high-volume EUS centers for esophageal cancer (≥50 EUS/endoscopist/y). From 1994 to 2003, 244 patients underwent EUS in the low-volume center. In this center, no specific measures to pass a stenotic tumor or to perform fine-needle aspiration were taken. The criterion standard in the low-volume EUS center was postoperative TNM stage. In the high-volume centers, 670 EUS investigations for esophageal cancer were performed (with dilation if needed), with postoperative TNM stage with or without fine-needle aspiration as the criterion standard. In the low-volume center, results of EUS for T 3 staging in patients in whom passage of the EUS probe was possible were almost comparable to those of the high-volume centers for sensitivity (85% versus 88%–94%) but were lower for specificity (57% versus 75%–90%). Results for T 1 and T 2 stages were lower in the low-volume center than in the high-volume centers for sensitivity (58% versus 75%–90%) and specificity (87% versus 94%–97%). In the low-volume center, sensitivities of EUS for regional (45% versus 63%–89%) and celiac (19% versus 72%–83%) lymph nodes were lower than those from high-volume centers, whereas specificities (75% versus 63%–82% and 99% versus 85%–100%, respectively) were comparable. Results in the low-volume EUS center were worse when the EUS probe could not pass the stricture, which occurred in almost 30% of patients. It was concluded that EUS performed in a low-volume EUS center compared unfavorably with that performed in high-volume EUS centers. This study suggests that preoperative staging by EUS, like the evaluation of CT examinations, should be performed by experienced and dedicated physicians to optimize the selection of patients who could undergo esophageal resection.
Curative treatment options
Early Esophageal Neoplasia
For many years, surgery was considered the treatment of choice for all patients who had esophageal cancer, including high-grade intraepithelial neoplasia (HGIN) and esophageal cancer confined to the mucosa. Histologic examination of surgical specimens showed, however, that there was no or only a minimal risk of metastases in mucosal esophageal cancer. Moreover, surgery is associated with a mortality of 3% to 5% and a morbidity of 30% to 40% in high-volume centers (>20 procedures/y) or with experienced surgeons. In low-volume centers (≤20 procedures/y) or with less experienced surgeons, the mortality rate of esophageal resection may increase to above 20%.
The endoscopic treatment options for HGIN or early esophageal cancer include ablative therapies and endoscopic mucosal resection (EMR). Ablative therapies are based on the premise that injury to the metaplastic and dysplastic Barrett’s epithelium will lead to the restoration of the normal squamous epithelium in an anacid environment. EMR involves local snare excision of the lesion. It has also been used to resect the entire at-risk BE segment to reduce the risk of recurrence. The advantage of EMR compared with ablative techniques is that complete histopathologic assessment of the resected specimen is possible.
Ablative Therapy
The most commonly used ablative techniques in BE in the last 5 years have been photochemical destruction by photodynamic therapy and thermal destruction by argon plasma coagulation. Other techniques include multipolar electrocoagulation and destruction of BE by liquid nitrogen or ultrasonic energy. These techniques are associated with local complications (such as strictures) due to the deep thermal injury (mainly photodynamic therapy) and the possibility of buried glandular mucosa (all methods).
Recently, a balloon-based circumferential endoscopic radiofrequency device (HALO360) was introduced (BARRX Medical, Sunnyvale, California) ( Fig. 4 ). It consists of a high-power radiofrequency energy generator, sizing balloon catheters, and ablation catheters. Sharma and colleagues were the first to report 1-year findings of a study that assessed dose response, safety, and efficacy of circumferential endoscopic radiofrequency ablation (RFA) of metaplastic BE without dysplasia using the HALO360 system. In the first phase of the study, the dosimetry phase, an energy level of 10 J/cm 2 was found to be optimal, and this level was used for the effectiveness phase. A second RFA procedure was performed when BE was still present at 1 or 3 months. In the effectiveness phase, 70 patients were enrolled. At 12 months’ follow-up, complete BE eradication was achieved in 70% of patients. There were no strictures and no buried glandular mucosa. In a follow-up study, with the help of a more focal RFA device (HALO90), a 98% eradication rate of BE was achieved. Another large United States series that included cases of HGIN achieved an eradication rate of HGIN of 90%, with only moderate results for eradicating all BE (54%). These rates were achieved using only the circumferential RFA device.
