ORIGINAL ARTICLE: Clinical Endoscopy

Abbrscopstain

DISCto th

See C

Copy0016http:

Rece

322

A case series on the use of circumferential radiofrequencyablation for early esophageal squamous neoplasias in patientswith esophageal varices

eviatioic submed lesio

LOSURis publi

ME se

right ª-5107/$//dx.do

ived Ma

GAST

Wen-Lun Wang, MD, PhD,1 I-Wei Chang, MD, PhD,2 Chien-Chuan Chen, MD,3 Chi-Yang Chang, MD, PhD,1

Lein-Ray Mo, MD,1 Jaw-Town Lin, MD, PhD,1,3,4 Hsiu-Po Wang, MD,3 Ching-Tai Lee, MD1

Kaohsiung, Taipei, Taiwan

Background and Aims: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality forearly esophageal squamous cell neoplasias (ESCNs). However, the feasibility of RFA for ESCNs in the setting ofesophageal varices has not been reported.

Methods: We retrospectively enrolled 8 consecutive patients with cirrhosis (Child-Pugh score �6) with early flat-type ESCNs (high-grade intraepithelial neoplasia/intramucosal cancer, and Lugol unstained lesion [USL] length �3cm extending �1/2 the circumference) on or adjacent to esophageal varices, for which circumferential RFA wasapplied as the initial treatment. The primary endpoint was a complete response at 12 months, and the secondaryendpoints were adverse events and procedure-related mortality.

Results: The mean USL length was 5.3 cm (range, 3–10 cm), and the average length of the treatment area was 7.5cm (range, 5–12 cm), with an average procedure time of 31.9 min (range, 25–40 min). After circumferential RFA, 3adverse events were recorded, including 2 intramucosal hematomas and 1 mucosal laceration, all of which spon-taneously resolved without further management. No massive bleeding, perforation, stricture, or hepatic failureoccurred after the procedure. Six of the 8 patients achieved a complete response after single circumferentialRFA, but 2 had residual squamous neoplasias. After additional focal-type RFA treatment, all achieved a completeresponse at 12 months. No neoplastic progression or recurrence occurred during a median follow-up period of21.6 months (range, 13–42 months).

Conclusions: RFA was associated with good treatment results, no neoplastic progression, and an acceptableadverse event profile for the treatment of early ESCNs in patients with well-compensated cirrhosis and esophagealvarices. (Gastrointest Endosc 2017;85:322-9.)

Heavy alcohol consumption is a well-known cause of expectancy, interventions for early esophageal squamous

esophageal cancer and liver cirrhosis.1 Recent advancesin imaging-enhanced endoscopy have made the early diag-nosis of superficial esophageal cancer possible,2,3 and thuspatients with alcoholic cirrhosis associated with superficialesophageal cancer spreading over esophageal varices havebeen increasingly reported.4-6 Even though patients withcirrhosis and portal hypertension have a shortened life

ns: ESCN, esophageal squamous cell neoplasia; ESD, endo-ucosal dissection; RFA, radiofrequency ablation; USL, un-n.

E: All authors disclosed no financial relationships relevantcation.

ction; p. 427.

2017 by the American Society for Gastrointestinal Endoscopy36.00i.org/10.1016/j.gie.2016.06.045

rch 1, 2016. Accepted June 17, 2016.

ROINTESTINAL ENDOSCOPY Volume 85, No. 2 : 2017

cell neoplasias (ESCNs) on or adjacent to esophageal vari-ces are still warranted, especially in those with well-compensated cirrhosis and those who may be candidatesfor liver transplantation.

Endoscopic resection is a well-established treatmentmodality for early ESCNs.7,8 However, treating ESCNswith esophageal varices is challenging because of the risk

Current affiliations: Department of Internal Medicine, E-Da Hospital/I-ShouUniversity, Kaohsiung (1), Department of Pathology, E-Da Hospital/I-ShouUniversity, Kaohsiung (2), Department of Internal Medicine, NationalTaiwan University Hospital, Taipei (3), School of Medicine and Big DataResearch Centre, Fu Jen Catholic University, New Taipei City, Taiwan (4).

Reprint requests: Hsiu-Po Wang, MD, Department of Internal Medicine,National Taiwan University, No.1, Changde St., Zhongzheng Dist., TaipeiCity 10048, Taiwan. Alternate contact: Ching-Tai Lee, MD, Department ofInternal Medicine, E-Da Hospital/I-Shou University, No.1, Yida Road,Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan.

www.giejournal.org

Figure 1. A representative patient (case 2) with early esophageal squamous neoplasia on small esophageal varices who was treated with circumferentialRFA. A, Conventional white-light imaging showing an esophageal varix at 6 o’clock. B, Lugol staining showing multiple Lugol-voiding lesions on or adja-cent to the varices, C, After RFA, the epithelium and the neoplasia were ablated. D, Close-up image of mucosa and esophageal varices after RFA. E, Onemonth after primary RFA, the epithelium had almost recovered with ulcer scarring. F, Lugol staining showing no residual lesions, and a biopsy alsoconfirmed complete remission. RFA, radiofrequency ablation.

Wang et al RFA for early ESCN with esophageal varices

of hemorrhage associated with many endoscopic thera-pies, along with the intrinsic coagulopathy seen in patientswith cirrhosis. As a result, most endoscopists are hesitantto use this technically challenging procedure.

Endoscopic radiofrequency ablation (RFA) is a rapidlyevolving therapeutic modality, and recent studies haveshown its efficacy and safety in eradicating dysplastic

www.giejournal.org

Barrett esophagus,9,10 as well as flat-type early ESCNs.11-15

However, the feasibility regarding its use in the settingof esophageal varices and cirrhosis has not previouslybeen reported. Therefore, in this pilot study we aimed toassess the efficacy and safety of RFA for early ESCNs inpatients with well-compensated cirrhosis accompanied byesophageal varices.

Volume 85, No. 2 : 2017 GASTROINTESTINAL ENDOSCOPY 323

Figure 2. A representative patient (case 3) with early ESCN on large esophageal varices. A, Conventional white-light imaging showing a flat reddish lesionon several large varices. B, Lugol staining showing a Lugol-voiding lesion occupying half of the esophageal circumference with a mosaic small Lugol-voiding background. C, Two months before the RFA procedure, band ligation was performed to eradicate the varices. D and E, White-light and Lugolchromoendoscopy imaging showing that the varices had become flattened. F, Circumferential RFA was performed, and easy bleeding was notedwhen moving down to another diseased segment. However, the bleeding stopped spontaneously after the procedure. G and H, One month after primaryRFA, the epithelium had almost recovered with ulcer scaring. I, At 12 months, Lugol staining showed no residual lesions. ESCN, esophageal squamous cellneoplasia; RFA, radiofrequency ablation.

RFA for early ESCN with esophageal varices Wang et al

METHODS

Patient selectionAn endoscopic RFA system was installed at our institu-

tion in 2011. From January 2011 to December 2014, 95 pa-tients were diagnosed with early ESCNs at EDa Hospital.Fourteen had cirrhosis and esophageal varices. From thiscohort, we retrospectively identified 8 consecutive patientswith well-compensated cirrhosis (Child-Pugh score �6)with esophageal varices and concomitant newly diagnosedhistologically proven early-stage ESCNs (squamous high-grade intraepithelial neoplasms and intramucosal squa-mous carcinomas), who received balloon-based RFA asthe initial treatment. All of the enrolled patients had

324 GASTROINTESTINAL ENDOSCOPY Volume 85, No. 2 : 2017

completely flat (type 0–IIb) early ESCNs, located overlyingor adjacent (beside or at the same longitudinal level of theesophagus) to the small esophageal varices (Fig. 1). Inaddition, Lugol chromoendoscopy (1.5%) showedunstained lesions (USL) occupying more than 50% of thecircumference of the esophagus and extending morethan 3 cm longitudinally in each case. The histologicresults were obtained by carefully taking 2 biopsysamples at the lesions away from the varices. Weevaluated the severity of the esophageal varices based onthe endoscopic findings according to the classificationdefined by the Japanese Research Society of PortalHypertension.16 If the varices were large or tortuous,band ligation to eradicate the varices was performed

www.giejournal.org

Wang et al RFA for early ESCN with esophageal varices

2 cm away from the distal side of the early ESCN 2 monthsbefore the RFA procedure (Fig. 2). Patients wereexcluded if any of the following exclusion criteria weremet: (1) those having varices with red wale marks or ahistory of variceal bleeding; (2) magnifying endoscopyshowed the intraepithelial papillary capillary loop as typeV3 (m3 invasion) or Vn (submucosal invasion) pattern,according to the classification of the microvasculararchitecture of superficial esophageal carcinoma17;(3) length of USL-bearing esophagus >12 cm; (4) endo-scopic US or CT showed lymphadenopathy. The Institu-tional Review Board of E-Da Hospital approved the study.All patients provided informed consent after a full explana-tion of the use of RFA and alternative treatment options.

Radiofrequency ablationAll the enrolled patients received balloon-based RFA as

the initial treatment, which was performed by a single en-doscopist (W.L.W.) using a HALO 360 system (Covidien GISolutions, Sunnyvale, Calif) as described previously.11,12

The HALO 360 system consists of a balloon ablation cath-eter, an energy generator, and a sizing balloon. All RFA pro-cedures were performed with the patients under conscioussedation or anesthesia. Before the RFA procedure, Lugolstaining was performed to determine the location andsize of the lesions. We used a 12 J/cm2, clean, 12 J/cm2

regimen to treat the first 4 patients, and double ablation(12 J/cm2) without cleaning14 for the others to minimizethe risk of bleeding.

Outcome measures and follow-upAfter the RFA procedures, the patients were given eso-

meprazole 40 mg daily and sucralfate suspension 5 mL(200 mg/mL) 4 times daily for 1 month. The patientsthen received follow-up endoscopy at 1, 3, and 6 monthsafter the procedure and every 6 months thereafter. If resid-ual squamous intraepithelial neoplasms were detected,focal-type RFA (Halo 90 system, Covidien) (12 J/cm2, 3applications) for high-grade dysplasia/mucosal cancer orargon plasma coagulation (ENDOPLASMA, Olympus,Tokyo, Japan; 1.5 L/min, 35 W) for low-grade dysplasiawere applied every 3 months until complete remissionwas achieved. The primary endpoint was a histologicallycomplete response at 12 months, defined as the absenceof squamous neoplasia in Lugol staining and any biopsysample. The secondary endpoints were adverse eventsincluding bleeding, perforation, stenosis (when a standard9.8-mm diameter endoscope failed to pass through thestenosis), and procedure-related mortality.

RESULTS

Clinical and endoscopic characteristics of thepatients

The clinical and endoscopic characteristics of the 8 pa-tients with early ESCNs are shown in Table 1. The

www.giejournal.org

average age at the time of detection was 55.9 years(range, 42–63 years). All the patients were male, and allhad alcoholic cirrhosis (Child-Pugh score �6) and anESCN located overlying or beside the esophageal varices.Five of the patients had a baseline diagnosis of high-grade dysplasia, and 3 had a diagnosis of mucosal squa-mous cell carcinoma. The mean length of Lugol USLswas 5.3 cm (range, 3–10 cm), and the average length ofthe treatment area was 7.5 cm (range, 5–12 cm). One pa-tient (case 3) received band ligation to eradicate the vari-ces 2 months before the procedure (Fig. 2). All thepatients underwent balloon-based circumferential RFA asthe initial treatment. Four patients were treated with a 12J/cm2, clean, 12 J/cm2 regimen, and the others were treatedwith double ablation (12 J/cm2) without cleaning. Theaverage procedure time from insertion of the sizingballoon to ablation was 31.9 min (range, 25–40 minutes;Table 2).

Adverse events and outcomes after RFAThree of the 8 patients developed adverse events imme-

diately, including 2with intramucosal hematomas and 1withmucosal laceration (Table 2). The 2 cases of intramuralhematomas were self-limiting without causing massivebleeding (Fig. 3). One case with mucosal laceration wasobserved during sizing. The patient was then admitted for2 days for observation and administration of prophylacticantibiotics. No further endoscopic or surgical interventionwas required. All the patients tolerated the procedure,with an uneventful postoperative course. In the patientstreated with the 12 J/cm2, clean, 12 J/cm2 regimen, easybleeding was detected during scraping of the coagulum.However, the bleeding was stopped after a secondablation in all of these patients. There were no reports ofmassive bleeding, perforation or stricture, and none of thepatients developed decompensated cirrhosis or hepaticfailure after the procedure. After single circumferentialRFA, 6 of the 8 patients achieved a complete response;however, 2 had residual high-grade intraepithelial squa-mous neoplasias. After additional therapy with focal-typeRFA (Halo 90) for thosewith residual high-grade intraepithe-lial squamous neoplasias, and argon plasma coagulation for apatient with residual small low-grade dysplasia, all 8 patientsachieved a complete response at 12 months. No neoplasticprogression was noted during a median follow-up periodof 21.6 months (range, 13–42 months). However, 1 patientwas diagnosed with multiple hepatocellular carcinomas at3 months after RFA, and died at 18 months after transarterialchemoembolization treatment (case 4).

DISCUSSION

In this pilot study, we investigated the efficacy andsafety of RFA for early ESCNs in patients with cirrhosiscomplicated with esophageal varices. All the ESCNs were

Volume 85, No. 2 : 2017 GASTROINTESTINAL ENDOSCOPY 325

TABLE 1. The clinical and endoscopic characteristics of 8 patients who received radiofrequency ablation

Patient Age (years) Cause of cirrhosis Child-Pugh score PT/INR (s) Platelet count (1000/mm3)

1 53 ALC 5 11.6/1.18 110

2 42 ALC þ HBV 6 13.7/1.34 97

3 52 ALC 5 12.2/1.19 116

4 76 ALC 6 12.1/1.18 129

5 57 ALC 5 10.2/0.97 119

6 61 ALC 6 10.1/1.0 124

7 47 ALC þ HCV 5 10.2/1.01 109

8 59 ALC 6 14.1/1.39 106

Mean/median 55.9 � 10.2 – 5.5 11.8/1.16 114 � 10.3

PT, Prothrombin time; INR, international normalized ratio; EV, esophageal varix; ALC, alcohol consumption; M, middle esophagus; L, low esophagus; SCC, squamous cellcarcinoma; HBV, hepatitis B virus; HGD, high-grade dysplasia; HCV, hepatitis C virus.

RFA for early ESCN with esophageal varices Wang et al

eradicated by RFA at 12 months, and the safety profileswere satisfactory. No neoplastic progression occurred dur-ing the follow-up period, and although the adverse eventrate was higher than that reported for patients withoutcirrhosis who received RFA,11-15 most of the adverse eventswere self-limiting and acceptable.

Patients with alcoholic cirrhosis have been reported tobe at high risk of ESCN due to alcohol abuse or thepossible carcinogenic effects of previous endoscopic injec-tion sclerotherapy.18,19 Although patients with cirrhosisand portal hypertension have a shortened life expectancy,interventions for ESCNs on or adjacent to esophageal vari-ces are still warranted, especially in those with well-compensated cirrhosis and those who may be candidatesfor liver transplantation. Patients with liver cirrhosis whoundergo esophagectomy still have high rates of operativemorbidity and mortality despite advancements in surgicalcritical care.20 Thus, endoscopic resection is currently themost commonly used method to treat early ESCNs, withthe advantages of large resection and histologic staging.7

Some case reports and series have reported thesuccessful use of EMR or endoscopic submucosaldissection (ESD) for early esophageal neoplasias inpatients with cirrhosis and esophageal varices.21-23

However, the procedures were done only after completeeradication of the esophageal varices. Two studiesdescribed successful ESD for early ESCNs with esophagealvarices, but the procedure required a high level of tech-nical expertise.5,6 However, endoscopic resection, eitherEMR or ESD, carries a high risk of disturbing the underly-ing esophageal varices in patients with cirrhotic portalhypertension, which may lead to a high risk of bleeding.In addition, a high level of endoscopic expertise is requiredfor such procedures. As a result, most endoscopists arehesitant to use this procedure, and more convenient andsafer methods to treat these high-risk patients are needed.

Endoscopic RFA is an effective and safe procedure totreat early esophageal flat-type neoplasia. To the best ofour knowledge, the present study is the first to investigate

326 GASTROINTESTINAL ENDOSCOPY Volume 85, No. 2 : 2017

the feasibility of RFA for treating ESCNs on or adjacent toesophageal varices. The complete response rates weresatisfactory and comparable with those in previous reportsthat demonstrated the clinical outcomes of endoscopicresection for ESCNs in typical cases.5 Diligent monitoringfor hemostasis is still indicated, however the safetyprofiles were favorable. In our series, 2 of the 8 patients(25%) developed intramural hematomas during the RFAprocedure, which is higher than previous reportsincluding patients without esophageal varices (<1%).11-15

We speculate that intramural hematomas may developdue to bleeding from perforated veins connecting the vari-ces, and that this could be stopped by the coagulation ef-fect of RFA. Thus, both cases were self-limiting withoutbleeding or the need for further management. Whetherbanding all varices before the RFA procedure could be asafer strategy to eliminate the adverse events requiresfurther studies in the future.

Compared with other tissue-destructive treatments suchas argon plasma coagulation or photodynamic therapy,24,25

RFA has some advantages, including a uniform, controlledablation depth and lower adverse event rate. An increasingnumber of studies have shown good efficacy and safety ofRFA in treating early ESCNs. Several studies have reportedthat the maximal ablation depth of RFA should reach themuscularis mucosa layer only,26,27 and thus theoreticallyit should be safe for superficial neoplasias over the esoph-ageal varices, which are located in the submucosal layer.Based on our results, the application of RFA may not injurethe varices, using double ablation with or without a clean-ing regimen. Both regimens are effective and had a goodsafety profile. A recent study compared the efficacy andsafety of RFA in treating ESCNs; they found Lugol stainingand a single hit with 12 J/cm2 (single application, no clean-ing) was the favored circumferential RFA technique.14 Thecleaning step with scraping of the coagulum maypotentially increase the risk of bleeding in patients withcirrhosis. Although the complete eradication rate inpatients who did not undergo cleaning was relatively

www.giejournal.org

TABLE 1. Continued

Serum albumin(g/dL)

Locationof EVs

Location ofneoplasia

(level from incisor, cm)Grade ofneoplasia

Maximal degree ofcircumferenceextension (%)

Length ofunstained lesions (cm)

3.6 M þ L 26-34 SCC 50 8

3.4 L 32-37 SCC 75 6

4.1 M þ L (ligation) 26_29 HGD 50 3

3.2 M þ L 26_31 HGD 50 5

3.9 M þ L 26-29 HGD 50 3

3.2 M þ L 22-32 HGD 100 10

4.1 L 32-35 SCC 75 3

3.0 M þ L 31-35 HGD 50 4

3.5 � 0.4 – – – – 5.3 � 2.6

TABLE 2. Outcome and adverse events after radiofrequency ablation

Patient

Length oftreatmentarea (cm)

Balloonsize (mm) Regimens of RFA

Proceduretime (min) Adverse events

CR afterprimary RFA

Additionaltreatment

CR at12 months

1 10 25 12 J–12 J 29 IH – HALO 90 þ2 8 28 12 J–12 J 28 ML – HALO 90 þ3 5 28 12 J–12 J 25 – þ – þ4 6 25 12 J–12 J 30 – þ – þ5 5 22 12 J–clean–12 J 32 – þ – þ6 12 22 12 J–clean–12 J 40 – þ APC (LGD) þ7 5 22 12 J–clean–12 J 35 – þ – þ8 5 25 12 J–clean–12 J 36 IH þ – þMean/median 7.0 � 2.7 25 – 31.9 � 4.9 3/8 (37.5%) 2/8 (25%) – 8/8 (100%)

RFA, Radiofrequency ablation; ESCN, esophageal squamous cell neoplasias; CR, complete response; IH, intramural hematoma; HALO 90, focal-type RFA; ML, mucosal laceration;APC, argon plasma coagulation; LGD, low-grade dysplasia.

Wang et al RFA for early ESCN with esophageal varices

lower, the residual lesions could still be totally eradicatedwith additional focal-type RFA. However, the number ofpatients included is very small, so the conclusionsregarding the efficacy of the different treatment regimensin patients with esophageal varices may require furtherinvestigation.

Optimal staging of early ESCNs before the RFA proce-dure is of paramount importance, yet is inevitably impairedin cases with underlying varices. Assessing depth of inva-sion is based on the combination of endoscopic stagingand taking biopsy samples. Yet taking biopsy samples inthe presence of varices is probably dangerous, and thismay lead to fewer samples taken and a risk for sampling er-ror. So, our data should not be considered as evidence forusing RFA in non–flat-type lesions (type IIa/IIc). Alternativeapproaches should be considered for these lesions, suchas (1) rubber-band ligation without resection for small le-sions and especially in the case of severe comorbidity,23

www.giejournal.org

(2) temporary transjugular intrahepatic portosystemicshunt with subsequent endoscopic resection, or (3)(chemo)radiotherapy.

Dysplastic Barrett’s esophagus also occasionally de-velops in patients with varices4,28; however, no studieshave reported the feasibility of RFA in this population.Therefore, further studies are needed to elucidate whetherRFA can be used safely and effectively for Barrett’s esoph-agus with varices. This pilot study is limited by the rela-tively low number of cases from a single institution. Alarge-scale study with long-term follow-up is required tovalidate our findings.

In conclusion, RFA was associated with good treatmentresults, no neoplastic progression, and an acceptableadverse event profile for the treatment of early ESCNs inpatients with compensated cirrhosis and esophageal vari-ces. However, further studies with long-term follow-up toevaluate its efficacy and safety profile are needed.

Volume 85, No. 2 : 2017 GASTROINTESTINAL ENDOSCOPY 327

Figure 3. A representative patient (case 8) complicated with an intramural hematoma after RFA. A and B, White-light and Lugol chromoendoscopy im-aging showing a flat early ESCN on several small varices. C, After RFA, an intramural hematoma developed, which resolved spontaneously and did notrequire any treatment. D, At 6 months, Lugol staining showing a good treatment effect. RFA, radiofrequency ablation.

RFA for early ESCN with esophageal varices Wang et al

ACKNOWLEDGMENTS

This work was supported by a grant (MOST-103-2314-B-650-006) from the Ministry of Science and Technology,Taiwan and E-Da Hospital (EDAHP105024).

REFERENCES

1. World Health Organization. Global Status Report on Alcohol andHealth 2011. Available at: http://www.who.int/substance_abuse/publications/global_alcohol_report. Accessed April 16, 2014.

2. Lee CT, Chang CY, Lee YC, et al. Narrow-band imaging with magnifyingendoscopy for the screening of esophageal cancer in patients with pri-mary head and neck cancers. Endoscopy 2010;42:613-9.

3. Lee YC, Wang CP, Chen CC, et al. Transnasal endoscopy with narrow-band imaging and Lugol staining to screen patients with head andneck cancer whose condition limits oral intubation with standardendoscope (with video). Gastrointest Endosc 2009;69:408-17.

4. Palmer WC, Di Leo M, Jovani M, et al. Endoscopic management ofhigh-grade dysplastic Barrett’s esophagus with esophageal varices.Gastrointest Endosc 2015;81:997.

5. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopicsubmucosal dissection for superficial esophageal cancer in patientswith cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.

328 GASTROINTESTINAL ENDOSCOPY Volume 85, No. 2 : 2017

6. Hsu WH, Kuo CH, Wu IC, et al. Superficial esophageal squamous cellcarcinoma over esophageal varices treated by endoscopic submucosaldissection. Gastrointest Endosc 2014;79:833-4.

7. Fujishiro M, Yahagi N, Kakushima N, et al. Endoscopic submucosaldissection of esophageal squamous cell neoplasms. Clin GastroenterolHepatol 2006;4:688-94.

8. Lee CT, Chang CY, Tai CM, et al. Endoscopic submucosal dissection forearly esophageal neoplasia: a single center experience in SouthTaiwan. J Formos Med Assoc 2012;111:132-9.

9. Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation inBarrett’s esophagus with dysplasia. N Engl J Med 2009;360:2277-88.

10. Phoa KN, van Vilsteren FG, Weusten BL, et al. Radiofrequency ablationvs endoscopic surveillance for patients with Barrett esophagus andlow-grade dysplasia: a randomized clinical trial. JAMA 2014;311:1209-17.

11. Wang WL, Chang IW, Chang CY, et al. Circumferential balloon-basedradiofrequency ablation for ultralong and extensive flat esophagealsquamous neoplasia. Gastrointest Endosc 2014;80:1185-9.

12. Wang WL, Chang IW, Chen CC, et al. Radiofrequency ablation versusendoscopic submucosal dissection in treating large early esophagealsquamous cell neoplasia. Medicine 2015;94:e2240.

13. Bergman JJ, Zhang YM, He S, et al. Outcomes from a prospective trialof endoscopic radiofrequency ablation of early squamous cellneoplasia of the esophagus. Gastrointest Endosc 2011;74:1181-90.

14. He S, Bergman J, Zhang Y, et al. Endoscopic radiofrequency ablationfor early esophageal squamous cell neoplasia: report of safety and

www.giejournal.org

Wang et al RFA for early ESCN with esophageal varices

effectiveness from a large prospective trial. Endoscopy 2015;47:398-408.

15. van Vilsteren FG, Alvarez Herrero L, Pouw RE, et al. Radiofrequencyablation for the endoscopic eradication of esophageal squamoushigh grade intraepithelial neoplasia and mucosal squamous cell carci-noma. Endoscopy 2011;43:282-90.

16. The general rules for recording endoscopic findings on esophagealvarices. Jpn J Surg 1980;10:84-7.

17. Kumagai Y, Inoue H, Nagai K, et al. Magnifying endoscopy, stereo-scopic microscopy, and the microvascular architecture of superficialesophageal carcinoma. Endoscopy 2002;34:369-75.

18. Kokudo N, Sanjo K, Umekita N, et al. Squamous cell carcinoma afterendoscopic injection sclerotherapy for esophageal varices. Am JGastroenterol 1990;85:861-4.

19. Takasaki M, Horimi T, Takahashi I, et al. Superficial esophageal carci-noma detected on extensive esophageal varices before endoscopic in-jection sclerotherapy. Gastrointest Endosc 1997;45:96-8.

20. Lu MS, Liu YH, Wu YC, et al. Is it safe to perform esophagectomy inesophageal cancer patients combined with liver cirrhosis? InteractCardiovasc Thorac Surg 2005;4:423-5.

21. Inoue H, Endo M, Takeshita K, et al. Endoscopic resection of carcinomain situ of the esophagus accompanied by esophageal varices. SurgEndosc 1991;5:182-4.

GIE on Twitter

GIE now has a Twitter account. Followerposted and will receive up-to-the-minuteviews, podcasts, and articles. Search on Tof GIE’s tweets.

www.giejournal.org

22. Ciocirlan M, Chemali M, Lapalus MG, et al. Esophageal varices and earlyesophageal cancer: can we perform endoscopic mucosal resection(EMR)? Endoscopy 2008;40(Suppl 2):E91.

23. Kunzli HT, Weusten BL. Endoscopic resection of early esophagealneoplasia in patients with esophageal varices: how to succeedwhile preventing the bleed. Endoscopy 2014;46(Suppl 1 UCTN):E631-2.

24. Ido K, Yamamoto H, Kawamoto C, et al. Esophageal varices obliteratedby photodynamic therapy for coexisting early esophageal carcinoma.Gastrointest Endosc 1997;45:420-3.

25. Tahara K, Tanabe S, Ishido K, et al. Argon plasma coagulation for super-ficial esophageal squamous-cell carcinoma in high-risk patients. WorldJ Gastroenterol 2012;18:5412-7.

26. Ganz RA, Utley DS, Stern RA, et al. Complete ablation of esophagealepithelium with a balloon-based bipolar electrode: a phased evalua-tion in the porcine and in the human esophagus. Gastrointest Endosc2004;60:1002-10.

27. Dunkin BJ, Martinez J, Bejarano PA, et al. Thin-layer ablation of humanesophageal epithelium using a bipolar radiofrequency balloon device.Surg Endosc 2006;20:125-30.

28. Palmer WC, Di Leo M, Jovani M, et al. Management of high gradedysplasia in Barrett’s oesophagus with underlying oesophageal varices:a retrospective study. Dig Liver Dis 2015;47:763-8.

s will learn when the new issues arenews as well as links to author inter-witter for @GIE_Journal and follow all

Volume 85, No. 2 : 2017 GASTROINTESTINAL ENDOSCOPY 329

本文献由“学霸图书馆-文献云下载”收集自网络，仅供学习交流使用。

学霸图书馆（www.xuebalib.com）是一个“整合众多图书馆数据库资源，

提供一站式文献检索和下载服务”的24 小时在线不限IP

图书馆。

图书馆致力于便利、促进学习与科研，提供最强文献下载服务。

图书馆导航：

图书馆首页 文献云下载 图书馆入口 外文数据库大全 疑难文献辅助工具