Trial Information

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

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.