ESD Versus EMR for Treatment of Early Barrett`s Adenocarcinoma

Barrett Adenocarcinoma Clinical Trial

Official title:

Water-jet Assisted Endoscopic Submucosal Dissection (ESD) Versus Endoscopic Mucosal Resection (EMR) for Treatment of Early Barrett`s Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01871636
• Other study ID #: EVKendo2013
• Status: Completed
• Phase: N/A
• First received: May 12, 2013
• Last updated: September 7, 2015
• Start date: December 2012
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: Evangelisches Krankenhaus Düsseldorf
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Conventional techniques of endoscopic mucosal resection (EMR) by snare resection do usually not achieve resection of gastrointestinal mucosal neoplastic lesions larger than 1 cm in diameter in a single piece. Complete R0 resection cannot be histologically confirmed. In contrast to EMR the technique of endoscopic submucosal dissection (ESD) allows en-bloc resection even of large neoplastic lesions. The waterjet-assisted ESD technology (WESD) allows pressure controlled injection of fluids through the tip of a recently developed HybridKnife®. Submucosal injection, circumferential cutting and dissection of lesions as well as coagulation of bleeding sources can be performed with the same device without need for changing the instrument. Our group reported on effective en-bloc resection of esophageal areas in all of 14 cases of an Erlangen porcine model. We subsequently compared WESD with EMR of predefined esophageal mucosal lesions in anesthetizised pigs in a randomized controlled trial. The results demonstrated that WESD more frequently achieved a complete resection with a significantly lower number of specimen. WESD caused no perforations and bleedings could be endoscopically managed during the procedure. In addition we recently reported on this technology in a first clinical trial on WESD for early Barrett`s neoplasia . The results indicated that WESD can be safely and effectively performed in the esophagus.

Therefore the primary objective of this study is to compare the R0 resection rate of ESD and EMR for visible lesions of HIgh grade intraepithelial neoplasia (HGIN) or esophageal adenocarcinoma (EAC). Secondary objectives are related to completeness of resection, safety of the procedures, the medium term outcome and comparison of costs.

Description:

Conventional techniques of endoscopic mucosal resection (EMR) by snare resection do usually not achieve resection of gastrointestinal mucosal neoplastic lesions larger than 1 cm in diameter in a single piece ("en-bloc"). En-bloc resection can even fail in cases of smaller lesions depending on their location and shape. Extension of EMR by piecemeal resection is therefore frequently required for removal of the targeted neoplastic area. However the histological evaluation of several specimen can usually not identify the outer margins of the neoplastic area. Thus complete R0 resection cannot be histologically confirmed. Histologically important additional information, e.g. infiltration of lymphatic vessels or submucosal infiltration may be missed in between resected specimen due to coagulation artifacts or left tissue bridges. In addition piecemeal EMR of early neoplasia in Barrett`s esophagus is associated with a high recurrence rate probably because of minor remnants of neoplastic tissue. In contrast to EMR the technique of endoscopic submucosal dissection (ESD) allows en-bloc resection even of large neoplastic lesions. Variations of this method have been increasingly used for various types of early gastrointestinal neoplasia mainly in Asian countries. In Japan ESD has been approved for treatment of selected cases of early gastric and colorectal neoplasia as an alternative to surgery. A recent meta-analysis of non-randomized controlled trials showed that ESD of early gastrointestinal tumors is superior to EMR in terms of en-bloc resection and curative resection rates but it is more time-consuming and is associated with higher rates of bleeding and perforation. A few small series on ESD were also reported from Western countries.

The waterjet-assisted ESD technology (WESD) allows pressure controlled injection of fluids through the tip of a recently developed HybridKnife®. Submucosal injection, circumferential cutting and dissection of lesions as well as coagulation of bleeding sources can be performed with the same device without need for changing the instrument. These options should accelerate the procedure and may increase its safety and efficacy. Experimental trials in ex vivo and in vivo pig models showed that the gastrointestinal mucosa of different sites can be effectively and safely lifted by gentle placement of the HybridKnife® on the wall and needleless injection of saline solution with pressures between 30 - 70 bar. Our group reported on effective en-bloc resection of esophageal areas in all of 14 cases of an Erlangen porcine model. We subsequently compared WESD with EMR of predefined esophageal mucosal lesions in anesthetizised pigs in a randomized controlled trial. The results demonstrated that WESD more frequently achieved a complete resection with a significantly lower number of specimen. WESD caused no perforations and bleedings could be endoscopically managed during the procedure.

Furthermore, we applied WESD for early gastric neoplasia in a prospective single center study. This study involved 29 consecutive patients. The results confirmed the experimental findings that WESD simplifies the ESD procedure and can be effectively and safely performed. Repici et al. applied the WESD methodology to colorectal neoplasia larger than 3 cm in diameter. Also this clinical study showed that WESD is a safe and effective method to provide en-bloc and curative resection of selected cases of colorectal neoplastic lesions.

In addition we recently reported on this technology in a first clinical trial on WESD for early Barrett`s neoplasia. The results indicated that WESD can be safely and effectively performed in the esophagus. It achieved en-bloc resection of early BE neoplasia in 27 of 30 patients. The rate of histologically complete resection (R0) was 38.5 % which was higher than previously reported for focal EMR of BE-EAC. We discussed that higher rates can be expected in case of well delineated lesions and definition of R0 resection as histologically complete resection of adenocarcinoma or HGIN. This definition would not consider LGIN at lateral margins as incomplete resection which is in accordance to a recent trial on ESD of early colorectal neoplasia. Possible remnants of LGIN seem to be clinically irrelevant because they are not considered as exclusion criteria for RFA after complete endoscopic removal of HGIN or EAC. RFA is considered to be the best available ablation technique for eradication of residual BE mucosa after focal EMR. On the other hand R0 resection of HGIN or EAC is considered to be important because a complete histological evaluation of the specimen minimizes the risk of overlooking criteria for advanced tumor stages (e.g. cancerous infiltration of lymphatic vessels or submucosal tissue) which are related with an increased risk of lymph node metastases thus requiring major surgery. The risk of a more advanced lesion is increased in visible lumps or nodules consisting of HGIN. In this context it should be considered that there is poor inter-observer agreement among pathologists in distinguishing HGD from intra-mucosal adenocarcinoma.

Therefore the primary objective of this study is to compare the R0 resection rate of ESD and EMR for visible lesions of HGIN or EAC. Secondary objectives are related to completeness of resection, safety of the procedures, the medium term outcome and comparison of costs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2015
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male, Female

• At least 18 years old

Exclusion Criteria:

• - Age under 18 years

• Health status ASA 4

• Pregnancy

• INR>2.0, Platelets < 70/nl

• Previous endoscopic or surgical treatment of BE neoplasia

• Neoplastic lesions which do not meet the inclusion criteria, in particular flat lesions (type 0-IIb)

• Additional areas of HGIN or AC

• Absence of a signed informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Barrett Adenocarcinoma
• Carcinoma in Situ
• High Grade Intraepithelial Neoplasia

Intervention

Procedure:
• Endoscopic mucosal resection
Endoscopic mucosal resection removes tissue in a piece meal technique or by snare limited to the mucosa.
• Waterjet-assisted ESD
The waterjet-assisted endoscopic submucosal dissection (WESD) technology allows pressure controlled injection of fluids through the tip of a recently developed HybridKnife®. Submucosal injection, circumferential cutting and dissection of lesions.

Device:
• HybridKnife
The waterjet-assisted endoscopic submucosal dissection (WESD) technology allows pressure controlled injection of fluids through the tip of a recently developed HybridKnife®. Submucosal injection, circumferential cutting and dissection of lesions.

Locations

Country	Name	City	State
Germany	Evangelisches Krankenhaus	Duesseldorf

Sponsors (1)

Lead Sponsor	Collaborator
Evangelisches Krankenhaus Düsseldorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histologically complete resection (R0 resection) of BE - HGIN or EAC		6 month	No
Secondary	Complete resection of the targeted neoplastic area		6 month	No
Secondary	Complete en-bloc resection of the targeted neoplastic area		6 month	No
Secondary	Determination of the procedural duration		6 month	No
Secondary	Determination of the 30-day morbidity and mortality		6 month	No
Secondary	Determination of the costs to achieve CR from HGIN or EAC		6 month	No