The study evaluated the use of single-operator peroral cholangioscopy (SOC) using the SpyGlass system in 16 liver transplant recipients with biliary complications. Two distinct cholangioscopic patterns of anastomotic strictures were identified - pattern A with mild findings and pattern B with severe findings. Patients with pattern A responded better to endoscopic therapy, requiring shorter stenting durations than pattern B. SOC allowed direct visualization of lesions, acquisition of biopsies, and identification of additional stones. The findings suggest SOC may help predict and guide management of biliary complications after liver transplant.

1. Prospective Evaluation of Single-
Operator Peroral Cholangioscopy in
Liver Transplant Recipients Requiring an
Evaluation of the Biliary Tract
Domingo Balderramo et al
Liver Transplantation: Volume 19, Issue 2, pages
199–206, February 2013
Presented by:
Dr. Amitesh Kumar
Moderator:
Dr. Neeraj Saraf

2. Introduction
• Biliary complications occur in upto 20% patients after deceased donor LT
• ERCP
 first-line therapeutic approach
- confirms diagnosis
- allows therapy
- success rate - 80% to 100% [1, 4, 6]
 limitations
- cannot directly visualize the bile duct
- cannot specify characteristics of stricture or filling defect
• Single-operator cholangioscopy (SOC) system using the SpyGlass direct
visualization system (Boston Scientific Corp., Natick, MA)
 Main indication:
o evaluation of indeterminate pancreatico- biliary strictures
o treatment of large, difficult to remove common bile duct stones
 high procedure success rate
 high accuracy in distinguishing benign and malignant lesions [12-17]

3. Aim of the study
To describe both cholangioscopic and
histological findings of biliary lesions in liver
transplant recipients using the SOC-SpyGlass
direct visualization system

4. Study Design
• Prospective
• Descriptive
• Single center - Hospital Clinic in Barcelona, a
tertiary care hospital

5. Study Population
• Inclusion criteria:
Adult recipients of deceased donor liver transplant with biliary
complications referred for ERCP between June 2009 and July 2011
• Exclusion criteria:
refusal to participate in the study
inability to provide informed consent
pregnancy
living donor liver transplant
previous Roux-en-Y hepaticojejunostomy
confirmed malignancy of the biliary tree
advanced liver failure
coagulopathy
hemodynamic instability
sepsis

6. Procedures
• ERCP and cholangioscopy - all patients
• Biliary sphincterotomy - if not done previously
• If anastomotic stricture present
 following were evaluated
-Borders -Ulcers -concentricity versus eccentricity
 2 patterns
a) scarring and minimal inflammatory changes
b) edema, ulceration and severe inflammatory changes
 2 - 4 biopsies taken
 stents placed as required
• If anastomotic stricture absent
 descriptive findings of anastomosis and bile duct recorded
 2 to 4 biopsies of anastomosis taken
 endoscopic therapy of any biliary complication (eg: stone removal)

7. Outcomes and Definitions
• Main outcome measure:
-feasibility of procedure
-adequate visualization
-ability to obtain biopsy
• Secondary outcomes
-impact on endoscopic therapy
-incidence of adverse events
-total cholangioscopy time
• Plastic stents removed every 3 months  stricture evaluated  If A.S. still
present  further therapy with balloon dilation and stent placement
• Stricture considered to be relieved- if no evidence of stenosis on
cholangiography and free passage of extraction balloon
• ERCP therapy defined as failing - when there was indication for percutaneous
transhepatic cholangiography or surgery during follow-up

8. RESULTS
• 23 patients met the inclusion criteria
• 7 patients were excluded
 hemodynamic instability (n = 2)
 bacterial infection (n = 2), cytomegalovirus infection (n = 1)
 recent T-tube extraction (n = 1)
 previous postsphincterotomy bleeding (n = 1)
• Finally, 16 patients were included
 anastomotic stricture -12
 CBD stones - 2
 bile leak - 1
 SOD – 1
• Complete SOC successful in 15 of 16 (93.8%)
In 1 patient, cholangioscope could not be advanced across the stricture
• 5patients - T-tube placed previously
• Total cholangioscopy time was 26.8 ± 10.1 minutes.

9. Summary of demographic and clinical
characteristics and cholangioscopic findings
SL
NO
SEX/
AGE
ETIOL
OGY
COMPLI
CATION
A.S.
TYPE
BORDER A.S. PATTERN ADDITIONAL
FINDINGS
NEED FOR
SURGERY
TIME FROM
LT to ERCP
(MNTH)
STENTING
PERIOD
(DAYS)
ERCP WITH
STENTING
1 M/54 HCV AS CONC IRR A STONES NO 13.8 238 4
2 M/65 HCV AS CONC IRR A NO NO 28.3 309 5
3 M/47 ALD AS CONC REG A NO NO 5.8 113 2
4 M/48 HCV AS ECC IRR A STONES NO 12.2 131 2
5 M/64 HCV AS CONC IRR A NO NO 4.2 175 3
6 M/65 HCV AS CONC IRR A NO YES 12.6 * *
7 F/49 HCV AS CONC IRR A NO NO 27.1 124 2
8 M/60 HCV,
HBV
AS CONC IRR A NO NO 64.5 195 3
9 M/45 HCV AS ECC IRR A NO NO 2.1 178 2
10 F/66 HCV AS CONC IRR B STONES YES 30.4 720 8
11 M/43 HCV AS ECC IRR B STONES NO 36.2 443 5
12 M/51 HCV AS ECC IRR B NO YES 7.6 207 3
13 F/73 HCV STONE REG CONT NO 153.8 - -
14 F/41` ALF STONE REG CONT NO 230.1 - -
15 F/45 ALF BILE
LEAK
REG CONT NO 1.9 101 1
16 M/48 HCV SOD REG CONT STONES 13.8 - -

10. Cholangioscopy Findings
• Two patterns in A.S.
(A) mild erythema and scarring
(n = 9)
(B) severe edema, erythema,
ulceration with sloughing (n = 3)
• Patients without A.S. - pale
mucosa, mild edema, no stenosis
(C)
• Biliary epithelium of native or
graft bile duct outside the
anastomosis - no significant
abnormalities
• Additional CBD stones noted
which were not seen in initial
cholangiograms for 5 patients
(31%) (D)

11. Clinical evolution according to cholangioscopic
findings in patients with A.S.
Characteristic Pattern A (n=9) Pattern B (n=3) P Value
Duration of stenting (days) 167±87 457±257 0.01
ERCP procedures with stenting 2.7±1.2 5.3±2.5 0.03
Success of endoscopic therapy [n(%)] 8(88.9) 1(33.4) 0.13

12. Characteristics of patients with A.S.
Variable Pattern A (n=9) Pattern B(n=3) P value
Baseline data
Age (years 55.6±8.4 53.9±11.4 0.81
Male sex [n(%)] 8(88.9) 2(66.7) 0.45
HCV etiology [n(%)] 8(88.9) 3(100) >0.99
Post liver transplant data
Bile leak[n(%)] 2(22.2) 0(0) >0.99
T – tube use[n(%)] 3(33.3) 0(0) 0.51
Acute cellular rejection[n(%)] 1(11.1) 0(0) >0.99
CMV infection[n(%)] 2(22.2) 0(0) >0.99
Hepatic artery thrombosis[n(%)] 1(11.1) 0(0) >0.99
Immunosuppression at ERCP[n(%)]
Tacrolimus 3(33.3) 2(66.7) 0.53
Cyclosporine 3(33.3) 0(0) 0.51
Mammalian target of rapamycin inhibitor 2(22.2) 1(33.3) >0.99
Prednisolone 4(44.4) 0(0) 0.49
Mycophenolate mofetil 2(22.2) 0(0) >0.99
ERCP data

13. • All patients with A.S. - followed up until the A.S. was resolved or
surgery or percutaneous transhepatic cholangiography was needed
• Stenting period: pattern B (457 days) > pattern A (167 days) [P = 0.01]
• Maximum number of stents placed in any patient = 4
• Response to endoscopic therapy: pattern A(88.9%) > pattern
B(33.4%) [P = 0.13]
• Complications: 1 patient (6.2%) - cholangitis
• 3 patients with A.S. underwent hepaticojejunostomy because:
I. inability to traverse the stricture with a guide wire
II. development of a liver abscess (unrelated to procedure)
III. lack of a response despite multiple sessions
• No restenosis during follow-up
• No significant differences in age, sex, post liver transplant evolution,
or time from transplant to ERCP between pattern A and pattern B

14. Histopathological Findings
• Adequate tissue – 81% patients
• Pattern A:
(1) Nuclear pseudostratification,
prominent nucleoli, focal
mucinous metaplasia, and focal
intraepithelial inflammatory
cells (mostly neutrophils)
(2) Subepithelial mucinous biliary
glands associated with a chronic
inflammatory infiltrate

15. • Pattern B:
(1) Moderate fibrinous material
with scattered neutrophilic
aggregates
(2) Mild nuclear
pseudostratification and
abundant intraepithelial
neutrophils
• Patients without A.S. - normal
columnar epithelial biliary cells
with basal nuclei
• There were no findings
compatible with graft rejection,
fungal infection, cytomegalovirus
infection, or post transplant
lymphoproliferative disorder

16. Discussion
• Outcomes of patients who develop A.S. or other
complications after liver transplant has improved with
advances in surgical, endoscopic and radiological
management [2-5, 29]
• The main findings of this study indicate that
(1) ERCP-guided SOC with the SpyGlass system is feasible
and can successfully be performed in LT recipients with
biliary complications
(2) 2 different cholangioscopic AS patterns can be easily
identified and may help to predict responses to therapy
(3) histological findings in ASs show nonspecific
inflammatory changes

17. • Responses to endoscopic treatment in LT recipients with A.S.
may differ according to the cholangioscopy pattern
• Patients with pattern A:
 responded better than patients
 required fewer days of stenting to achieve a final response to
endoscopic therapy
• Patients with Pattern B
 needed more ERCP sessions with stenting
 require prolonged therapy
 should be considered for early surgery if there is no good
response after 1 or 2 sessions to prevent a prolonged course
of ERCP and it’s complications

18. Suggested treatment algorithm based on findings of SOC

19. Limitations of the study
• Small sample size
• Single-center study
• Presence of a learning curve with this procedure
• Patients who underwent living donor LT or recipients
of transplants from donors after cardiac death, who
have a higher incidence of A.S. versus recipients of
cadaveric donors were not included

20. Conclusion
• ERCP-guided SOC with the SpyGlass system is
feasible and can be successfully performed in
liver tranplant recipients with biliary
complications
• Cholangioscopic findings of A.S. may predict the
response to ERCP therapy

21. Suggested future studies
• Further prospective studies comparing ERCP
alone to ERCP plus SOC
• Large prospective, multicenter study that could
evaluate predetermined criteria based on patient
characteristics, surgical characteristics of
transplants, radiographic and cholangiographic
criteria, and visual characteristics under SOC as
well as correlations of specific endpoints with the
outcomes of endoscopic therapy, the need for
surgical reinterventions, and clinical outcomes

22. REFERENCES• 1Thuluvath PJ, Pfau PR, Kimmey MB, Ginsberg GG. Biliary complications after liver transplantation: the role of
endoscopy.Endoscopy 2005;37:857–863.
• 2Safdar K, Atiq M, Stewart C, Freeman ML. Biliary tract complications after liver transplantation. Expert Rev Gastroenterol
Hepatol2009;3:183–195.
• 3Ayoub WS, Esquivel CO, Martin P. Biliary complications following liver transplantation. Dig Dis Sci 2010;55:1540–1546.
• 4Krok KL, Cárdenas A, Thuluvath PJ. Endoscopic management of biliary complications after liver transplantation. Clin Liver Dis2010;14:359–
371.
• 5Sharma S, Gurakar A, Jabbour N. Biliary strictures following liver transplantation: past, present and preventive strategies. Liver
Transpl 2008;14:759–769. 6Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction, its complications and management of biliary
complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome. Transpl Int 2011;24:379–
392.
• 7Kawai K, Nakajima M, Akasaka Y, Shimamotu K, Murakami K. A new endoscopic method: the peroral choledocho-pancreatoscopy (author's
transl) [in German]. Leber Magen Darm 1976;6:121–124.
• 8Nakajima M, Akasaka Y, Fukumoto K, Mitsuyoshi Y, Kawai K. Peroral cholangiopancreatoscopy (PCPS) under duodenoscopic guidance. Am J
Gastroenterol 1976;66:241–247.
• 9Rösch W, Koch H, Demling L. Peroral cholangioscopy. Endoscopy 1976;8:172–175.
• 10Urakami Y, Seifert E, Butke H. Peroral direct cholangioscopy (PDCS) using routine straight-view endoscope: first
report.Endoscopy 1977;9:27–30.
• 11Chathadi KV, Chen YK. New kid on the block: development of a partially disposable system for cholangioscopy. Gastrointest Endosc Clin N
Am 2009;19:545–555.
• 12Draganov PV, Lin T, Chauhan S, Wagh MS, Hou W, Forsmark CE. Prospective evaluation of the clinical utility of ERCP-guided
cholangiopancreatoscopy with a new direct visualization system. Gastrointest Endosc 2011;73:971–979.
• 13Ramchandani M, Reddy DN, Gupta R, Lakhtakia S, Tandan M, Darisetty S, et al. Role of single-operator peroral cholangioscopy in the
diagnosis of indeterminate biliary lesions: a single-center, prospective study. Gastrointest Endosc 2011;74:511–519.
• 14Chen YK, Parsi MA, Binmoeller KF, Hawes RH, Pleskow DK, Slivka A, et al. Single-operator cholangioscopy in patients requiring evaluation
of bile duct disease or therapy of biliary stones (with videos). Gastrointest Endosc 2011;74:805–814.
• 15Maydeo A, Kwek BE, Bhandari S, Bapat M, Dhir V. Single-operator cholangioscopy-guided laser lithotripsy in patients with difficult biliary
and pancreatic ductal stones (with videos). Gastrointest Endosc 2011;74:1308–1314.
• 16Siddiqui AA, Mehendiratta V, Jackson W, Loren DE, Kowalski TE, Eloubeidi MA. Identification of cholangiocarcinoma by using the Spyglass
SpyScope system for peroral cholangioscopy and biopsy collection. Clin Gastroenterol Hepatol 2012;10:466–471.

23. REFERENCES contd…
• 17Draganov PV, Chauhan S, Wagh MS, Gupte AR, Lin T, Hou W, Forsmark CE. Diagnostic accuracy of conventional and cholangioscopy-guided sampling
of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study.Gastrointest Endosc 2012;75:347–353.
• 18Wright H, Sharma S, Gurakar A, Sebastian A, Kohli V, Jabbour N. Management of biliary stricture guided by the SpyGlass direct visualization system in
a liver transplant recipient: an innovative approach. Gastrointest Endosc 2008;67:1201–1203
• 19Parsi MA, Guardino J, Vargo JJ. Peroral cholangioscopy-guided stricture therapy in living donor liver transplantation. Liver Transpl2009;15:263–
265.Direct Link:
• 20Hoffman A, Kiesslich R, Moench C, Bittinger F, Otto G, Galle PR, Neurath MF. Methylene blue-aided cholangioscopy unravels the endoscopic features
of ischemic-type biliary lesions after liver transplantation. Gastrointest Endosc 2007;66:1052–1058.
• 21Siddique I, Galati J, Ankoma-Sey V, Wood RP, Ozaki C, Monsour H, Raijman I. The role of choledochoscopy in the diagnosis and management of biliary
tract diseases. Gastrointest Endosc 1999;50:67–73
• 22Gürakar A, Wright H, Camci C, Jaboour N. The application of SpyScope® technology in evaluation of pre and post liver transplant biliary
problems. Turk J Gastroenterol 2010;21:428–432.
• 23Rerknimitr R, Sherman S, Fogel EL, Kalayci C, Lumeng L, Chalasani N, et al. Biliary tract complications after orthotopic liver transplantation with
choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc2002;55:224–231.
• 24Pfau PR, Kochman ML, Lewis JD, Long WB, Lucey MR, Olthoff K, et al. Endoscopic management of postoperative biliary complications in orthotopic
liver transplantation. Gastrointest Endosc 2000;52:55–63
• 25Thuluvath PJ, Atassi T, Lee J. An endoscopic approach to biliary complications following orthotopic liver transplantation. Liver Int2003;23:156–
162.Direct Link:
• 26Costamagna G, Tringali A, Mutignani M, Perri V, Spada C, Pandolfi M, Galasso D. Endotherapy of postoperative biliary strictures with multiple stents:
results after more than 10 years of follow-up. Gastrointest Endosc 2010;72:551–557.
• 27Dumonceau JM, Tringali A, Blero D, Devière J, Laugiers R, Heresbach D, Costamagna G; for European Society of Gastrointestinal Endoscopy. Biliary
stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2012;44:277–
298.
• 28Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, et al. A lexicon for endoscopic adverse events: report of an ASGE
workshop. Gastrointest Endosc 2010;71:446–454.
• 29Londoño MC, Balderramo D, Cárdenas A. Management of biliary complications after orthotopic liver transplantation: the role of endoscopy. World J
Gastroenterol 2008;14:493–497.