Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection (BEEPER)

Prospektiv-randomisierter Vergleich Von En-bloc- Versus Piecemeal-Resektion Von Barrett Neoplasien Des Ösophagus Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection

The study will compare EMR versus ESD technique (both combined with subsequent ablative therapy) of mucosal resection in Barrett's esophagus with regard to efficacy and risk in a long term setting.

Study Overview

• Status: Recruiting
• Conditions: Barrett Esophagus; Barrett Adenocarcinoma; Esophagus Neoplasm
• Intervention / Treatment: Procedure: Endoscopic mucosal resection; Procedure: Endoscopic submucosal dissection

Detailed Description

For Barrett's Esophagus neoplasia of at least LGIN up to early adenocarcinoma, the aim is to debulk or completely treat polypoid dysplastic or malignant lesions in Barrett's esophagus. The Endoscopic Mucosal Resection EMR has been established to be a less invasive, safe, and effective nonsurgical therapy. The most commonly employed modalities of EMR include snare resection with and without prior submucosal injection of fluid, and resection using a cap. Since resection of larger areas can only be done piece - by- piece this kind or resection is also called piecemeal resection or piecemeal EMR. Meanwhile, another endoscopic resection has been developed called Endoscopic Submucosal Dissection ESD.It enables complete resection of neoplasms that were impossible to resect en bloc by EMR. After circumferential cutting of the surrounding mucosa of the lesion, fluid is injected into the submucosa to elevate the lesion from the muscle layer, and subsequently the connective tissue beneath the lesion is dissected. As a basic principle on histopathological and oncological terms, the en bloc resection is to be preferred since resection integrity can be evaluated much more securely. However, complexity of this kind of resection technique as well as complication rates can be different and sometimes higher than with EMR. Current approach treating Barrett's esophagus is to eradicate both neoplastic as well as pre neoplastic or non neoplastic Barrett mucosa in order to lower the relapse risk. Current treatment standard is to combine resection of visible neoplastic areas with subsequent thermo-ablation such as RFA or APC, so this approach will also be the basis of the present study. Since RFA has the largest volume of data screened it shall be the preferred method of ablation in this study.In total, data situation ist inconsistent. Short- and Long term of EMR is excellent in centres(Pech et al, Gastroenterology 2014) whereas ESD achieved only suboptimal outcomes in tree minor western studies (Neuhaus et al. Endoscopy 2012, Höbel et al., Surg Endosc 2015, Chevaux et al. Endoscopy 2015). One randomised study published in 2016 (Terheggen et al. Gut 2016) had a higher rate of R0 resections with ESD on 40 patients but no difference in complete remissions in combination with RFA. Although, this study was not empowered sufficientliy, and also showed a higher complication rate on ESD . At present no randomised study data are availale to allow statements about long term developments, so we will set up this current randomised study. We will compare data with regard to efficacy (histological completeness and relapse rates), as well as risks, e.g. perforations and strictures or stenosis by scarring.

• Study Type: Interventional
• Enrollment (Estimated): 407
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Rösch, Prof. Dr.; Phone Number: 50098 + 49 40 7410; Email: t.roesch@uke.de
• Study Contact Backup: Name: Hanno Ehlken, Dr.; Phone Number: 18232 + 49 40 7410; Email: h.ehlken@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
    • Sub-Investigator: Katharina Zimmermann-Fraedrich, Dr.
    • Sub-Investigator: Guido Schachschal, PD Dr.
    • Sub-Investigator: Philip Dautel, Dr.
    • Contact: Thomas Rösch, Prof. Dr.; Phone Number: 50098 + 49 40 7410; Email: t.roesch@uke.de
    • Contact: Tania Ruppenthal; Phone Number: 50089 + 49 40 7410; Email: t.ruppenthal@uke.de
    • Sub-Investigator: Yuki B. Werner, Dr.
    • Sub-Investigator: Hanno Ehlken, PD Dr.
    • Sub-Investigator: Jocelyn de Heer, Dr.
    • Principal Investigator: Thomas Rösch, Prof. Dr.
    • Sub-Investigator: Karsten Ohlhoff, Dr.
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health
      • Contact: Pamela Beck; Phone Number: 321-841-6696; Email: Pamela.Beck@orlandohealth.com
      • Contact: Ginette Garcia De Djuro, CCMA; Phone Number: 321- 841-6649; Email: Ginette.GarciaDeDjuro@orlandohealth.com
      • Principal Investigator: Ji Young Bang, MD MPH
      • Sub-Investigator: Shyam Varadarajulu, MD
      • Sub-Investigator: Robert Hawes, MD
      • Sub-Investigator: Udayakumar Navaneethan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients to be treated for Barrett's esophagus by mucosal resection and following ablative therapy
• Barrett's mucosal extension up to 10 cm maximum.
• patient's ability for compliance to therapy
• signed Informed Consent

Exclusion Criteria:

• any lesion questionable to be resectable by mucosectomy, e.g. bulky lesions ≥10 mm in endoscopy und endosonography, suspected deep submucosal infiltration, ulcers, suspected or by FNA confirmed lymph node infiltration
• Barrett's esophagus > 10 cm
• lesions that would afford resection of more than 2/3rd of esophagal circumference
• two or more single Barrett's lesions with bulky HGIN or early cancer histology, not to be resectable in one half of esophageal circumference
• planned circumferencial resections
• very serious general illness and metastatic carcinoma
• coagulation disorder or anticoagulants that make biopsies and resections impossible
• American Society of Anesthesiologists (ASA) status > III
• pregnancy and lactation
• remainders or recurrences after therapeutic history of Barrett's espohagus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EMR; Endoscopic mucosal resection	Procedure: Endoscopic mucosal resection; Endoscopic resection is carried out using a double-channel scope. The lesion borders are marked with a coagulator. Saline liquid and sometimes epinephrine are injected into the submucosal layer to swell the area containing the lesion and elucidate the markings. The resected mucosa is lifted, then trapped and strangulated with a snare, and subsequently resected by electrocautery. Another method of EMR employs the use of a clear cap and prelooped snare inside the cap. After insertion, the cap is placed on the lesion and the mucosa containing the lesion is drawn up inside the cap by aspiration. The mucosa is caught by the snare and strangulated, and finally resected by electrocautery.; Other Names: EMR; Piecemeal EMR
Active Comparator: ESD; Endoscopic submucosal dissection	Procedure: Endoscopic submucosal dissection; After circumferential cutting of the surrounding mucosa of the lesion, fluid is injected into the submucosa to elevate the lesion from the muscle layer, and the connective tissue of the submucosa beneath the lesion is dissected subsequently.; Other Names: ESD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate of neoplastic Barrett's Esophagus, initial therapy success	Rate of complete and curative eradication, free of recurrence of neoplastic Barrett's Esophagus. Endoscopical diagnostic and negative histologies for any kind of neoplasia, measured in follow up control EGD 3 months after end of treatment	3 months after end of therapy (resection and ablation)
Eradication rate of neoplastic Barrett's Esophagus, initial therapy success	Rate of complete and curative eradication, free of recurrence of neoplastic Barrett's Esophagus. Endoscopical diagnostic and negative histologies for any kind of neoplasia, measured in follow up control EGD 9 months after end of treatment	9 months after end of therapy (resection and ablation)
Eradication rate of neoplastic Barrett's Esophagus	Rate of complete and curative eradication, free of recurrence of neoplastic Barrett's Esophagus. Endoscopical diagnostic and negative histologies for any kind of neoplasia, measured in follow up control 24 months after end of treatment	24 months after end of therapy (resection and ablation)
Eradication rate of neoplastic Barrett's Esophagus	Rate of complete and curative eradication, free of recurrence of neoplastic Barrett's Esophagus. Endoscopical diagnostic and negative histologies for any kind of neoplasia, measured in follow up control EGD 33 months after end of treatment	33 months after end of therapy (resection and ablation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate of complete Barrett's Esophagus, initial therapy success	Rate of complete and curative eradication, free of recurrence of neoplastic and non-neoplastic Barrett's Esophagus. Endoscopical diagnostics and negative histologies for any kind of neoplasia and Barrett's metaplasia measured in follow up control EGD 3 months after end of treatment	3 months after end of treatment (resection and ablation)
Eradication rate of complete Barrett's Esophagus, initial therapy success	Rate of complete and curative eradication, free of recurrence of neoplastic and non-neoplastic Barrett's Esophagus. Endoscopical diagnostics and negative histologies for any kind of neoplasia and Barrett's metaplasia measured in follow up control EGD 9 months after end of treatment	9 months after end of treatment (resection and ablation)
Eradication rate of complete Barrett's Esophagus, freedom of recurrence	Rate of complete and curative eradication, free of recurrence of neoplastic and non-neoplastic Barrett's Esophagus. Endoscopical diagnostics and negative histologies for any kind of neoplasia and Barrett's metaplasia measured in follow up control EGD 24 months after end of treatment	24 months after end of treatment (resection and ablation)
Eradication rate of complete Barrett's Esophagus, freedom of recurrence	Rate of complete and curative eradication, free of recurrence of neoplastic and non-neoplastic Barrett's Esophagus. Endoscopical diagnostics and negative histologies for any kind of neoplasia and Barrett's metaplasia measured in follow up control EGD 33 months after end of treatment	33 months after end of treatment (resection and ablation)
Recurrence rate of neoplastic Barrett's Esophagus, initial therapy success	rate of complete and curative eradication of neoplastic Barrett's Esophagus measured in follow up control EGD 3 months, Endoscopical diagnostic and negative histologies for any kind of neoplasia.	3 months after end of therapy (resection and ablation)
Recurrence rate of neoplastic Barrett's Esophagus, initial therapy success	rate of complete and curative eradication of neoplastic Barrett's Esophagus measured in follow up control EGD 9 months , Endoscopical diagnostic and negative histologies for any kind of neoplasia.	9 months after end of therapy (resection and ablation)
freedom of recurrence rate of complete Barrett's Esophagus, initial therapy success	Freedom of recurrence rate of neoplastic and non-neoplastic Barrett's Esophagus. Endoscopical diagnostics and negative histologies for any kind of neoplasia and Barrett's metaplasia measured in follow up control EGD 9 months (initial therapy success) after end of treatment	9 months after end of treatment (resection and ablation)
ESD success of resection	rate of en bloc and R0 resections among the initially by ESD resected tissues	2 days
EMR success of resection	Since with EMR resection success can only be measured for the depth of base initially, the second control EGD with negative histology has been chosen for Gold standard indication for resection success. After 2 negative bioptic controls a piecemeal resection of early carcinoma is classified as complete.	9 months after end of treatment (resection and ablation)
Surveillance of Barrett's mucosa after incomplete resections and recurrences	follow up of all cases with initially incomplete EMR or ESD resections as well as recurrences after resection and ablation	51 months
conclusions of Tumor Board in case of re resection and outcome if postitive cancer histology	any Treatment and follow up in case of positive cancer histology	51 months
Determination of differences in Barrett's esophagus subtypes: size	size of Barrett's mucosa, e.g. Prague Classification	3 months
Determination of differences in Barrett's esophagus subtypes: form	form of Barrett's mucosa	3 months
Determination of differences in Barrett's esophagus subtypes: patterns	patterns of Barrett's mucosa, e,g, Kudo Classification	3 months
Determination of differences in Barrett's esophagus subtypes: histologies	histological assessment of Barrett's mucosa	3 months
Intervention time	time requested for each resection and ablative sessions	18 months

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Thomas Rösch, Prof. Dr., Ph D, Director, Head of department

Publications and helpful links

General Publications

• Spechler SJ, Souza RF. Barrett's esophagus. N Engl J Med. 2014 Aug 28;371(9):836-45. doi: 10.1056/NEJMra1314704. No abstract available.
• Anders M, Bahr C, El-Masry MA, Marx AH, Koch M, Seewald S, Schachschal G, Adler A, Soehendra N, Izbicki J, Neuhaus P, Pohl H, Rosch T. Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection. Gut. 2014 Oct;63(10):1535-43. doi: 10.1136/gutjnl-2013-305538. Epub 2014 Jan 3.
• BARRETT NR. The oesophagus lined by columnar epithelium. Gastroenterologia. 1956;86(3):183-6. doi: 10.1159/000200553. No abstract available.
• BARRETT NR. The lower esophagus lined by columnar epithelium. Surgery. 1957 Jun;41(6):881-94. No abstract available.
• Dunbar KB, Spechler SJ. Controversies in Barrett esophagus. Mayo Clin Proc. 2014 Jul;89(7):973-84. doi: 10.1016/j.mayocp.2014.01.022. Epub 2014 May 24.
• Edgren G, Adami HO, Weiderpass E, Nyren O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut. 2013 Oct;62(10):1406-14. doi: 10.1136/gutjnl-2012-302412. Epub 2012 Aug 23. Erratum In: Gut. 2013 Dec;62(12):1820. Weiderpass Vainio, Elisabete [corrected to Weiderpass, Elisabete].
• Hobel S, Dautel P, Baumbach R, Oldhafer KJ, Stang A, Feyerabend B, Yahagi N, Schrader C, Faiss S. Single center experience of endoscopic submucosal dissection (ESD) in early Barrett's adenocarcinoma. Surg Endosc. 2015 Jun;29(6):1591-7. doi: 10.1007/s00464-014-3847-5. Epub 2014 Oct 8.
• Labenz J, Koop H, Tannapfel A, Kiesslich R, Holscher AH. The epidemiology, diagnosis, and treatment of Barrett's carcinoma. Dtsch Arztebl Int. 2015 Mar 27;112(13):224-33; quiz 234. doi: 10.3238/arztebl.2015.0224.
• Neuhaus H. Endoscopic mucosal resection and endoscopic submucosal dissection in the West--too many concerns and caveats? Endoscopy. 2010 Oct;42(10):859-61. doi: 10.1055/s-0030-1255724. Epub 2010 Sep 30. No abstract available.
• Pech O, May A, Manner H, Behrens A, Pohl J, Weferling M, Hartmann U, Manner N, Huijsmans J, Gossner L, Rabenstein T, Vieth M, Stolte M, Ell C. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology. 2014 Mar;146(3):652-660.e1. doi: 10.1053/j.gastro.2013.11.006. Epub 2013 Nov 20.
• Phoa KN, Pouw RE, Bisschops R, Pech O, Ragunath K, Weusten BL, Schumacher B, Rembacken B, Meining A, Messmann H, Schoon EJ, Gossner L, Mannath J, Seldenrijk CA, Visser M, Lerut T, Seewald S, ten Kate FJ, Ell C, Neuhaus H, Bergman JJ. Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II). Gut. 2016 Apr;65(4):555-62. doi: 10.1136/gutjnl-2015-309298. Epub 2015 Mar 2.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: ESD; EMR; Barrett Esophagus; Esophagus Neoplasm; endoscopic resection technique; ablation of esophageal mucosa
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Precancerous Conditions; Esophageal Neoplasms; Barrett Esophagus
• Other Study ID Numbers: PV5387

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO