Feasibility of Computer guided Volumetric Laser Endomicroscopy (VLE) Targeted Biopsies for Improved Detection of Early Barrett*s Neoplasia

Esophageal cancer (adenocarcinoma) is a amongst the deadliest cancers, with
5-year survival rates <15%. The incidence of esophageal cancer has rised
rapidly over the last decades. Patients with a condition called Barretts
esophagus are at increased risk of developing adenocarcinoma.
In BE the normal lining of squamous epithelium is replaced by metaplastic
columnar epithelium. BE is caused by gastrointestinal! acid reflux.

The estimated prevalence of BE in Europe is 1.6 per 100 people. The progression
to EAC develops through a stepwise process from BE to low-grade and high-grade
dysplasia, and eventually to EAC. Therefore, the standard of care for Barrett's
patients consists of regular surveillance with white-light endoscopy and
quadrantic random biopsies every two centimeter of the Barrett's segment, to
detect neoplasia in an early stage.

The current surveillance protocol is, however, hindered by several
difficulties. First, early esophageal neoplastic lesions are associated with
only subtte mucosa! changes and therefore difficult to detect upon white-light
endoscopy. The random biopsies one sample a small part of the Barrett segment,
leading to sample error. Third the current protocol is labarous and a burder
for the patient and the health care system.

The solution to improve the current surveillance protocol lies in enabling
better visualization of early neopltasia in BE, thereby increasing detection
rates. Volumetric Laser Endomicroscopy (VLE) is a system that enables 3D
scanning of the esophagus during an endoscopic procedure, showing subsurface
irregularities that are invisible during endoscopy. Furthermore, with the new
VLE laser marking system, suspicious area can directly be marked. This might
enable to take targeted biopsies in the future, instead of numerous random
biopsies. This will imrpove the current surveillance protocol.

Interpretation of a VLE scan, harboring a large amount of data, with the human
eye is complex. Therefore, the addition of a computer-assisted BE neoplasia
detection algorithm for VLE could further enhance the potential of the system
to improve BE surveillance.

The aim of this study is to test the feasibility of a VLE computer algorith
that could improve detection of early neoplasie in BE patients.

This study will be conducted at the Departments of Gastroenterology and
Hepatology of the Amsterdam AMC, location AMC/VUmc, the Catharina Hospital
Eindhoven, and St. Antonius Nieuwegein en de Videocoding group at the technical
university of Eindhoven.
The study consists of the following parts:

1) Performing a VLE scan during the endoscopy
2) Test the feasibility and its workflow of the computer algorithm for VLE, for
the detection of BE neoplasia.

Previous studies, of which one was conducted at the AMC (METC 2015_244,
METC_122) have evaluated the VLE laser marking system and found that the system
was feasible and safe. The NVision VLE System is non-invasive in nature. The
type of light delivered by the optical probe is equivalent in intensity to the
standard light source used and delivered by a standard endoscope; the
excitation of tissue by the light energy delivered by the optical biopsy system
is non-damaging and does not result in any thermal effects on tissue. The
expandable balloon of the guide sheath has the potential of causing lacerations
or * in very rare occasions * perforation of the esophagus when inflated above
maximum allowed pressure. A safety valve is included in the design ofthe
balloon to avoid this problem. In patients with an esophageal stricture, the
risk of laceration increases, and these patients are therefore excluded from
participation in this trial. The endoscopic procedure will take an estimated
30-60 minutes (estimated average 45 minutes) longer compared to the standard
endoscopy.

The VLE procedure is not expected to produce any additional discomfort or
unique risks to the subject as compared to those already associated with
endoscopy and biopsy.

The marking laser will have similar risks as the placement cautery marks with
the tip of an endoscopic snare, that is used in clinical setting to mark areas
or to delineate lesions. The risks of bleeding or perforation from marking the
site are minimal. The laser marks on the esophageal tissue will not affect
histopathological diagnosis, as the use of cautery marking in clinical setting
for delineation of lesions didn't affect histopathological diagnosis.

Below a brief summary is given of potential risks when using the NVision VLE
system. For extensive description, we direct you to the protocol, sections
Device Information and Structured Risk Analysis.

The NvisionVLE Imaging System contains two laser systems, one for imaging and a
second optional for marking tissue. The imaging laser is classified as Class
1M, while the marking laser is classified as a Class 4 Laser Product. Light
energy emitted by the NinePoint Medical! NvisionVLE Imaging System lies in the
invisible, near-infrared region of the electromagnetic spectrum. It cannot be
seen with the naked eye. Inadvertent exposure to laser light may cause skin or
eye damage. Precautions will be made to ensure that the optical probe portion
of the Optical Probe is inside the endoscope prior to transmitting laser energy
through the system. Laser energy can be transmitted during self-test, during
scanning (Ful! or Scout Scan) or marking (Manual Scan). Viewing the laser
output with certain optical instruments (for example eye loupes, magnifiers,
and microscopes) within a distance of 100 mm may pose an eye hazard. During
imaging, laser safety eyewear is not required. During laser marking, additional
safety steps must be taken (please see protocol). Warning: Always ensure the
distal end ofthe Optical Probe has been inserted into the body or an endoscope
prior to activating laser. Never look directly into the laser beam coming from
the system or reflected from a surface. Electrical and Mechanical Hazards: When
the exterior housing of the NvisionVLE Imaging System is not displaced, there
is no risk from high voltage risks from inside the system. Movement of the
system has to be done carefully and slowly. To reduce the risk of electric
shock, do not connect the system's input power connection to equipment that is
not protectively earth grounded. The participating expert endoscopists,
research nurses and researchers will receive training on the Nvision VLE
marking system prior to use.