Prospective Evaluation of Single-Operator Peroral Cholangioscopy

in Liver Transplant Recipients Requiring an Evaluation of the

Biliary Tract

Domingo Balderramo et alLiver Transplantation: Volume 19,

Issue 2, pages 199–206, February 2013Presented by:Dr. Amitesh Kumar Moderator:Dr. Neeraj Saraf

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 strictureso treatment of large, difficult to remove common bile duct

stones high procedure success rate high accuracy in distinguishing benign and malignant lesions

[12-17] 

SPYGLASS

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

Study Design

Prospective

Descriptive

Single center - Hospital Clinic in Barcelona, a tertiary care hospital

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

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 changesb) 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)

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

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.

Summary of demographic and clinical characteristics and cholangioscopic findings

SL NO

SEX/ AGE

ETIOLOGY

COMPLICATION

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 - -

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)

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

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

Time from LT to ERCP (months) 14.9(9.5) 24.7(15.1) 0.24

Time from LT to ERCP >12 MONTHS [n(%)]

6(66.7) 2(66.7) >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 and pattern B

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

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

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

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

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

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

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

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