Per-Oral Cholangioscopy (POCS) in Liver Transplantation Patients

Liver transplantation is a life-saving procedure for patients with liver
failure or end-stage liver disease. More than 25,000 liver transplant surgeries
are performed around the globe annually, with the majority taking place in
Europe (approx. 9000) and the Americas (approx. 9000). Among the most common
complications in both live donor and deceased donor liver transplantation
recipients are those of the biliary system, with an incidence of 5-32%. More
than half of the biliary complications observed in this population occur within
3 months postsurgery and contribute significantly to morbidity and mortality.
Multiple studies have described the nature of biliary complications of patients
after liver transplantation surgery. The most commonly reported biliary
complications are strictures and leaks. Biliary strictures account for up to
40-50% of biliary complications among liver transplantation patients. The
incidence of stricture differs depending on the type of liver transplant
performed. The incidence of biliary stricture among live donor liver recipients
is typically higher than the incidence among deceased donor liver recipients
(28-32% vs 5-15%). Furthermore, anastomotic strictures are observed among 5-15%
of deceased donor liver transplant recipients and 13-36% among live donor liver
transplant recipients, while non-anastomotic strictures are observed in up to
11% of the transplant recipient. Anastomotic strictures typically occur 3 or
more months post-surgery and may be due to a particularly small bile duct, the
use of inappropriate suture material, inadequate surgical technique, or
mucosa-to-mucosa anastomosis. These strictures occur more frequently among
deceased donor liver transplant patients (DDLT), are usually short and/or
localized, and endoscopic management yields excellent response rates.
Non-anastomotic strictures, on the other hand, are usually secondary to
immunologic or ischemic events and are usually longer than anastomotic
strictures. They may be present at multiple sites and, when visualized, may
appear diffuse. As the etiology of non-anastomotic strictures frequently
involves disrupted blood flow and more severe inflammatory processes, hepatic
artery stenosis and immunologic reaction due to ABO incompatibility may be
associated with these strictures. Non-anastomotic strictures are also less
responsive to endoscopic treatment with ERCP and present with a higher
recurrence rate than anastomotic strictures. Standard treatment for post-liver
transplant strictures includes balloon dilation and multiple stent placement
with monitoring at every 3 months. Patients with anastomotic strictures who
undergo balloon dilation and stenting have a successful outcome in up to 90% of
cases. Endoscopic management is, therefore, the first-line treatment in this
group of patients. Nonanastomotic stricture cases are more difficult to manage
and in those patients, life-long
annual surveillance after stent removal is required. Biliary casts and stones
may develop in up to 18% of liver transplant patients. Casts and
stones usually occur at anastomotic sites and may result from debris build-up
at these locations. Symptomatic casts and stones are treated with endoscopic
cast and stone removal techniques.

The current standard for diagnosis of biliary complications in liver transplant
patients includes imaging with ultrasound, MRI, CT, and/or ERCP. ERCP-based
therapies have also
become the first-line approach to the treatment of post-surgical biliary
complications and have, in most cases, replaced surgical management of biliary
strictures. However, there are still significant challenges in both the
diagnosis and ERCP-based therapy of bile duct strictures.
ERCP provides imaging of the biliary system using fluoroscopy which does not
provide much insight into the aspect of the biliary mucosa and ERCP-guided
cannulation of narrow ducts and tight strictures may be difficult or impossible.

The first generation SpyGlass Direct Visualization System (SpyGlass DVS) has
consistently exhibited efficacy comparable to ERCP in helping diagnosis based
on visualization and tissue sampling from the biliary system. Investigators
have shown that the SpyGlass DVS can help reliably diagnose biliary system
abnormalities as part of patient evaluation prior to or post-liver
transplantation. In an American cohort of 6 patients with suspicion of
malignancy and 4 patients with biliary complications post-liver transplantation
surgery,
investigators were able to visualize the biliary system with SpyGlass DVS and
take adequate biopsy samples, when needed, in 100% of cases. Further, in a
European cohort of 16 patients, epithelial mucosa patterns visualized with
SpyGlass DVS were associated with time to resolution of biliary complications
post-liver transplant surgery as well as with patient outcome. In a Korean
cohort of 15 patients post-living donor liver transplant (LDLT) surgery,
visualization of the hepatobiliary ducts with SpyGlass DVS was achieved in 93%
of cases and guidewire placement was successful in 60% of cases in which
guidewire placement by conventional methods had failed. In addition, published
case studies affirm that the evaluation and treatment of the hepatobiliary
system with conventional methods fails, success can be achieved with SpyGlass
DVS. Cholangioscopy in post-liver transplantation patients may be further
improved using the second-generation SpyGlass DS system due to its improved
image quality and catheter maneuverability.
A multi-center study is warranted to establish whether visualization with Spy
DS can provide clinically meaningful additional information to that gained from
an ERCP alone in patients with post-liver transplantation biliary
complications.

• To demonstrate the clinical utility of POCS in cadaveric donor or live donor
liver transplantation patients referred for endoscopic
retrograde cholangiopancreatography (ERCP) in the setting of a clinical
suspicion of post-liver transplant bile duct stricture(s).

• To generate a hypothesis for a possible randomized controlled trial (RCT)
comparing ERCP alone to ERCP with POCS in
patients referred for ERCP post-liver transplantation.

This is a prospective, multi-center, non-randomized, observational, consecutive
case series,
which will compare ERCP and cholangioscopy with SpyGlass DS or DS II procedure
at 5-10 centers.

or

This is a prospective, multi-center, non-randomized, observational, consecutive
case series,
which will determine the relevance of combining an ERCP procedure with POCS
(cholangioscopy) using SpyGlass DS or DS II which will be done in 5-10 centers.

not applicable

Nature and Exctent of Burden:
• ERCP and ERCP/PCCS procedure: 30 min.
• Follow-up 72 hour post-procedure: 30 min.
•• Liver Function Tests Assessment
• Follow-up 30 days post-procedure: 30 min.
•• Liver Function Tests Assessment
•• If required: US/MRI/CT/MRCP
• Follow-up 3 months post-procedure: 30 min.
•• Liver Function Tests Assessment
•• If required: US/MRI/CT/MRCP
• Follow-up 12 months post-procedure: 30 min.
•• Liver Function Tests Assessment
•• If required: US/MRI/CT/MRCP

Risks and Benefits Associated with participation:
The SpyGlass* DS and its equivalent SpyGlass* DS II are intended to provide
direct visualization of the pancreaticobiliary system, including the hepatic
ducts as stated in the DFU.

Benefits to the subject could potentially include better diagnostic accuracy
and therapeutic efficacy as compared to ERCP alone when SpyScope* DS Access and
Delivery Catheter or the SpyScope* DS II Access and Delivery Catheter is used
with SpyGlass* DS or DS II.

Digital Controller. Indeed, potential benefits may include, for example,
successful visualization and diagnosis of lesions, better identification of
filling defects, and removal of large and/or impacted bile duct stone(s).

The risks associated with the use of the SpyGlass DS or DS II are documented in
the Directions for Use and clinical data for the system is currently reviewed
by the Sponsor. The following conclusion was reported as it pertains to
SpyGlass-related adverse events:
Evaluation of bile duct disease and biliary stone therapy can be safely
performed with a high
success rate by using the single-operated cholangioscopy system.