Neoplastic Barrett Esophagus: Endoscopic Piecemeal vs. En Bloc Resection

NCT ID: NCT03427346

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 407 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2025-10-31

Brief Summary

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.

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.

Conditions

Barrett Esophagus; Barrett Adenocarcinoma; Esophagus Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EMR

Endoscopic mucosal resection

Group Type: ACTIVE_COMPARATOR

Endoscopic mucosal resection

Intervention Type: PROCEDURE

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.

ESD

Endoscopic submucosal dissection

Group Type: ACTIVE_COMPARATOR

Endoscopic submucosal dissection

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Other Intervention Names

EMR; Piecemeal EMR; ESD

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Thomas Rösch

Director of Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Rösch, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Ph D, Director, Head of department

Locations

Orlando Health

Orlando, Florida, United States

Site Status: RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Site Status: RECRUITING

Countries

United States; Germany

Central Contacts

Thomas Rösch, Prof. Dr.

Role: CONTACT

t.roesch@uke.de

+ 49 40 7410 ext. 50098

Hanno Ehlken, Dr.

Role: CONTACT

h.ehlken@uke.de

+ 49 40 7410 ext. 18232

Facility Contacts

Pamela Beck

Role: primary

Pamela.Beck@orlandohealth.com

321-841-6696

Ginette Garcia De Djuro, CCMA

Role: backup

Ginette.GarciaDeDjuro@orlandohealth.com

321- 841-6649

Thomas Rösch, Prof. Dr.

Role: primary

t.roesch@uke.de

+ 49 40 7410 ext. 50098

Tania Ruppenthal

Role: backup

t.ruppenthal@uke.de

+ 49 40 7410 ext. 50089

References

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.

Reference Type: BACKGROUND

PMID: 24389236 (View on PubMed)

BARRETT NR. The oesophagus lined by columnar epithelium. Gastroenterologia. 1956;86(3):183-6. doi: 10.1159/000200553. No abstract available.

Reference Type: BACKGROUND

PMID: 13384591 (View on PubMed)

BARRETT NR. The lower esophagus lined by columnar epithelium. Surgery. 1957 Jun;41(6):881-94. No abstract available.

Reference Type: BACKGROUND

PMID: 13442856 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24867396 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22917659 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25294533 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25869347 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20886404 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24269290 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25731874 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25162890 (View on PubMed)

Other Identifiers

PV5387

Identifier Type: -

Identifier Source: org_study_id