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Biliary Stricture

The Achilles Heel of Pediatric Living Donor Liver Transplantation

Yoshizumi, Tomoharu MD1; Harada, Noboru MD1; Mori, Masaki MD11

doi: 10.1097/TP.0000000000002573
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Since a 1989 report demonstrating successful living donor liver transplantation (LDLT), living donors have been increasingly used to overcome the disparity between organ supply and demand, especially in the cases of pediatric patients. Although short-term graft outcomes after LDLT have improved significantly because of progress in surgical techniques and immunosuppression, biliary stricture (BS) remains the Achilles heel of pediatric LDLT and is the major cause of significant long-term morbidity. BS results in poor quality of life or even in graft loss after LDLT, with a reported incidence of BS after pediatric LDLT of 10% to 35%. The suggested risk factors for BS after LDLT are hepatic arterial thrombosis, bile duct ischemia, acute cellular rejection, older donor age, and ABO incompatibility. Duct-to-duct biliary reconstruction, which enables an endoscopic approach to be attempted after BS, is the preferred technique for LDLT. Endoscopic approaches are less invasive and more convenient for recipients than surgical and percutaneous interventions. However, the major cause of end-stage liver disease in pediatric recipients is biliary atresia, and hepaticojejunostomy is needed to reconstruct the bile duct because of the lack of recipient bile duct. Endoscopic approaches for BS are usually less favorable in patients with hepaticojejunostomy than in those with duct-to-duct biliary reconstruction. Treatment options for BS after hepaticojejunostomy at many centers thus involve interventional radiology or surgical reintervention. Although endoscopic approaches remain controversial in pediatric recipients, several reports have shown them to be safe and less invasive.

1 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Received 16 October 2018. Revision received 2 November 2018.

Accepted 4 December 2018.

The authors declare no funding or conflicts of interest.

T.Y. wrote the paper. N.H. and M.M. gave critical comments.

Correspondence: Tomoharu Yoshizumi, MD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. (yosizumi@surg2.med.kyushu-u.ac.jp).

In this issue of Transplantation, Sanada et al1 reported a retrospective analysis of 15 years’ experience focusing on the risk factors, treatments, and long-term prognosis for biliary anastomotic strictures (AS) in pediatric living donor liver transplantation (LDLT) (n = 290). They classified biliary stricture (BS) into AS or nonanastomotic stricture (NAS), defined as hepaticojejunal AS and intrahepatic bile duct stricture, respectively. The overall incidence of BS was 17.9%, including AS in 46 cases (15.9%) and NAS in 6 cases (2%).

The cause of posttransplant NAS, which often leads to graft loss, is still unclear, though immunological injuries, such as recurrent primary sclerosing cholangitis or ABO incompatibility, and hepatic arterial problems are thought to increase the risk of this severe complication. However, the cause and treatment of NAS remain unclear in a small number of patients who develop NAS. Given that Sanada et al were unable to address these issues regarding NAS sufficiently in their previous work, we have also avoided discussing them here.

The 5-year cumulative incidences of AS in the lost stent and no-biliary stent groups were 16.2% and 24.5%, respectively, compared with 4.2% in the external stent group. Although Sanada et al did not present P values for the differences between the groups, hepaticojejunostomy without an external stent was an independent risk factor for AS. Their first choice of treatment for AS was nonsurgical, such as percutaneous transhepatic biliary drainage (PTBD) or double balloon enteroscopy (DBE), followed by surgical reanastomosis. DBE was applied in patients with a body weight >15 kg with mild intrahepatic bile duct dilatation, because of instrumental and technical limitations. A total of 103 interventions using DBE were performed in 37 patients aged 13.1 years (age range 3.7 to 23.8 y), with success and recurrence rates of 76.8% and 69.9%, respectively.

Sanada et al clearly demonstrated that an external stent reduced the incidence of AS. A Japanese group has exclusively used transcholedocal external biliary stents for duct-to-duct (DD) biliary anastomosis in LDLT since 2003 and recently reported an incidence of AS of 8.5% in right lobe LDLT.2 A Korean group recently reported that absence of biliary stents was an independent risk factor for biliary complications in adult LDLT with DD biliary reconstruction.3 In contrast, a Taiwanese group reported that they did not use biliary stents, even in pediatric LDLT, because a single microsurgeon routinely performed microsurgical techniques without the need for biliary stents.4 Microsurgical biliary reconstruction is an alternative technique in LDLT and could reduce BS without the need for biliary stents. However, it is necessary to bear in mind that although microsurgical biliary reconstruction may be possible under certain situations, the appropriate use of external stents remains the easiest way to reduce BS in LDLT, regardless of technical expertise.

Advances in endoscopic instruments and techniques have led us to consider DBE for the endoscopic treatment of BS. According to Sanada et al, the recurrence rate of AS after DBE was 69.9%, whereas that after PTBD was 18.8%. They stated that endoscopic intervention was only performed by balloon dilatation without stent placement, resulting in the high incidence of recurrence after DBE compared with PTBD.1 The period of bile duct patency could be prolonged following endoscopic balloon dilatation combined with stenting using single or multiple plastic tubes, compared with balloon dilatation alone.5,6 Balloon dilatation and stent replacement should be performed every 2-4 months until the stricture is resolved. Indeed, the common therapy for BS with DD biliary reconstruction after liver transplantation involves endoscopic balloon dilatation and multiple stents placements followed by periodic replacement of the stents.7 Sanada et al did not describe the detailed technical problems associated with DBE in this issue. Report of DBE after LDLT are lacking; however, reports of DBE in patients with altered gastrointestinal anatomy, such as Whipple procedure, have been increasing.6,8,9 The success rate of scope insertion to the anastomotic site varies from 76% to 100%,6,9 with excessive looping of the endoscope, excessive afferent loop length, and afferent loop adhesions all contributing to failed insertion.6 Adverse event such as cholangitis, biliary laceration, or microperforation occurred in 4% to 7% of patients who underwent DBE.6,8 DBE-related morbidity and mortality, quality of life, and retransplantation rates are important parameters to consider when assessing the respective treatment modalities and should be clarified by a large cohort or prospective study.

In summary, instrumental innovations will make DBE the first choice of treatment for BS and increase the success rate, even in pediatric patients, while stent placement after dilatation may decrease the recurrence rate.

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Acknowledgments

We thank Cathel Kerr, PhD, and Susan Furness, PhD, from Edanz Group (www.edanzediting.com/ac) for editing drafts of this manuscript.

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