2. 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.
4. To describe both cholangioscopic and
histological findings of biliary lesions in liver
transplant recipients using the SOC-
SpyGlass direct visualization system
6. 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
7. 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)
8. 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
9. 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.
10. SL
NO
SEX/
AGE
ETIO
LOG
Y
COMPL
ICATIO
N
A.S.
TYPE
BORDE
R
A.S.
PATTERN
ADDITIONA
L FINDINGS
NEED
FOR
SURGER
Y
TIME FROM
LT to ERCP
(MNTH)
STENTIN
G
PERIOD
(DAYS)
ERCP
WITH
STENTIN
G
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
11. 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)
12. 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
13. 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
14. 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
16. 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
17. 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
18. 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
20. 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
21. 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
22. 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
23. 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.
24. 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.