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Presented by:
Dr. Amitesh
Kumar
Moderator:
Dr. Neeraj Saraf
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]
To describe both cholangioscopic and
histological findings of biliary lesions in liver
transplant recipients using the SOC-
SpyGlass direct visualization system
Prospective
Descriptive
Single center - Hospital Clinic in Barcelona,
a tertiary care hospital
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
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)
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
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.
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
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)
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
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
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
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
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
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
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
Suggested treatment algorithm based on findings
of SOC
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
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
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
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Prospective evaluation of single operator peroral cholangioscopy in liver

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Prospective evaluation of single operator peroral cholangioscopy in liver

  • 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
  • 5. Prospective Descriptive Single center - Hospital Clinic in Barcelona, a tertiary care hospital
  • 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
  • 15. 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
  • 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
  • 19. Suggested treatment algorithm based on findings of SOC
  • 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
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