Cell Biochem Biophys DOI 10.1007/s12013-014-0473-8

ORIGINAL PAPER

The Efficacy and Safety of Endoscopic Balloon Dilation Combined with Stenting in Patients with Biliary Anastomotic Strictures After Orthotopic Liver Transplantation Chunyan Peng • Chao Ma • Guifang Xu • Shanshan Shen • Ying Lv • Xiaoping Zou

Ó Springer Science+Business Media New York 2015

Abstract Endoscopic balloon dilation combined with stenting has been increasingly used in managing biliary anastomotic strictures (BAS) after orthotopic liver transplantation (OLT). However, data on the efficacy and safety vary among different studies. To obtain reliable estimates for the efficacy and safety of this endoscopic combination therapy in post-OLT BAS. A systematic search was conducted in the literature published until June 2012. The outcomes of individual study were transformed into comparable data using the Freeman–Tukey double arcsine transformation method. Fixed-effect or random-effect models were built to simulate the outcomes. Subgroup analysis and meta-regression were used to explore the sources of clinical heterogeneity. Clinical resolution and recurrence were defined as the primary outcomes and complications and mortality as secondary outcomes. Nineteen studies (15 retrospective, 4 prospective; 17 fulltexts, 2 abstracts) were included, with a total of 745 patients. Fully covered self-expandable metal stent was only reported in one study, achieving a resolution rate of 92.3 %, recurrence rate of 8.3 %, and complication rate of 7.7 %. For 18 studies using plastic stents, the pooled resolution rate was 86 % (95 % CI 80–91 %; I2 = 74.7 %).

Chunyan Peng and Chao Ma consider are co-first authors. C. Peng  G. Xu  S. Shen  Y. Lv  X. Zou (&) Department of Gastroenterology, The Drum Tower Hospital Affiliated to Medical School of Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, People’s Republic of China e-mail: [email protected] C. Peng  C. Ma Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China

Abstracts, study design, and the delay from OLT to BAS diagnosis were contributing factors for heterogeneity in resolution. The pooled recurrence rate was 9 % (95 % CI 5–13 %; I2 = 59.6 %). Longer stenting duration predicted less recurrence (OR = 0.95, p = 0.002). The pooled complication rate was 14 % (95 % CI 8–21 %, I2 = 71.2 %). No procedure-related mortality was reported. Endoscopic balloon dilation combined with stenting is a relatively effective and safe modality in post-OLT BAS. Keywords Endoscopic balloon dilation  Stent  Biliary anastomotic stricture  Liver transplantation

Introduction Choledochocholedochostomy has become the preferred method of biliary reconstruction in adults undergoing orthotopic liver transplantation (OLT) for liver diseases except sclerosing cholangitis. Its advantages include preserving sphincter of Oddi function while providing easy endoscopic access to the biliary system [1]. However, this modality is still associated with high rates of biliary anastomotic stricture (BAS) [2]. BAS has been reported to occur in 4–9 % of OLT patients [3–6] and accounts for approximately 80 % of biliary strictures. It affects the longterm prognosis of post-OLT patients, which causes complications from graft loss to even death. Long-term management of post-OLT BAS remains clinically challenging, though it has evolved from primary surgical management to predominant endoscopic treatment. Currently, endoscopic retrograde cholangiopancreatography (ERCP) has been advocated as the first-line approach for BAS after choledochocholedochostomy [7]. Previous studies have indicated that endoscopic balloon

123

Cell Biochem Biophys

dilation followed by stenting with periodic exchange can achieve resolution rates of 50–100 % [7–11] and maintain more durable bile duct patency than monotherapy of balloon dilation [8, 12]. However, there is still no consensus on the optimal endoscopic management strategy, including stent number, stenting duration, and stent types (e.g., plastic versus metal stent). Individual studies with multiple stents used in post-OLT BAS reported improved outcomes, which may be explained by the fact that multiple stents can maintain maximal dilation in luminal diameter, better remodel bile ducts, and possibly decrease the collapsibility of biliary strictures after stent removal [13]. Although a recent systematic review favored multiple stents in treating benign biliary strictures [14], these results should be viewed with discretion. In this study, a fixed-effect model was performed to pool the outcomes in spite of an anticipated heterogeneity across the included studies. Further, it did not separate patients with BAS from those with other forms of stricture. The reported stent number and stenting duration were also controversial. With the conventional approach, the stent is kept in bile duct for at least 12 months. However, using an accelerated exchange approach (every 2 weeks) in the study by Morelli et al., stenting duration was reduced to 107.6 days, with a satisfactory resolution rate of 87 % [15]. Still, the optimal stenting duration and its impact on clinical outcomes remain elusive. In addition to the controversies about stent number and duration, stent type is also disputable. Covered self-expandable metal stents (CSEMS) seem to be attractive alternatives for plastic stents for benign biliary strictures in previous studies [16, 17], but there is no comparable study available on plastic stents with CSEMS for the treatment of post-OLT BAS. The aforementioned studies are predominantly retrospective and limited by their small sample sizes. More importantly, considerable heterogeneity exists in the published studies because of discrepancies in study design, therapeutic routes, no differentiation of patients with BAS and non-BAS, stent types, stent numbers, and stenting duration. Therefore, we conducted this meta-analysis of the relevant studies to investigate possible sources of disagreement in stenting variables and to estimate the efficacy and safety in endoscopic balloon dilation and stenting in treating patients with post-OLT BAS.

Methods Search Methods and Study Selection Articles were identified by a computer-assisted search of the relevant medical literature published in English. This

123

review was performed independently by two of the authors (PCY and MC) using PubMed, Embase/Ovid, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Cochrane Database of Abstracts of Reviews of Effects from their inception until June 2012. Search terms used were ‘‘biliary stricture’’, ‘‘liver transplantation’’, and ‘‘endoscopic therapy’’. The Boolean term ‘‘and/or’’ was used to combine the above terms. Searches were restricted to studies conducted in humans. Also, we hand searched the reference lists of retrieved articles and published reviews for other relevant articles that might be missed during the initial search process. Additionally, the studies were screened for potential duplicates, and only the publications with the most recent data were considered. Studies published only in abstract form were also included. The studies were identified based on the following inclusion criteria: (1) included adults with post-OLT BAS, (2) involved endoscopic balloon dilation combined with stenting, (3) reported efficacy and recurrence data (e.g., the number or proportion of resolution in patients treated by this endoscopic approach, and the number or proportion of recurrence in patients achieving resolution after stent removal), and (4) reported at least ten consecutive patients treated by this endoscopic approach. Exclusion criteria were (1) patients who failed in previous endoscopic therapy or who were diagnosed as refactory anastomotic strictures, (2) studies with pooled data for BAS and NonBAS, (3) investigations with pooled data for endoscopic and percutaneous transhepatic procedures, and (4) balloon dilation and/or stenting only by percutaneous transhepatic procedures. Data Extraction Two authors (PCY and MC) reviewed article titles and abstracts to identify the relevant studies according to the prespecified criteria. We did not contact the authors of the studies to request incomplete or unpublished data. The same two authors reviewed the manuscripts and extracted the data independently. Disagreement was resolved by discussion with the senior author (ZXP). The following data were collected study design, author, year of publication, country of the study, enrollment period, mid-year (the median of the range of year during which the study was conducted), median time from OLT to BAS diagnosis, number of patients included, median or mean age, male proportion, sphincterotomy (yes or no), stent type (plastic or metal), stent number (single or multiple stents based on the endoscopic protocols provided in the studies), total ERCP procedures, median or mean number of ERCP per patient, median or mean number of maximal stents per patient, median or mean stenting duration, clinical

Cell Biochem Biophys

resolution, stricture recurrence, complications, mortality, and median or mean follow-up period. Outcomes and Definitions The primary outcomes were (1) clinical resolution, defined as no stricture in cholangiogram at the completion of stent removal and no subsequent requirement for any interventional procedures; and (2) recurrence, defined by both clinical documentation and ERCP-documented recurrence of stricture after removing stents. The secondary outcomes were (1) complications, defined as adverse events after endoscopic therapy (e.g., cholangitis, pancreatitis, perforation, stent migration, or hemorrhage); and (2) mortality, defined as ERCP- or stent-related death. Statistical Analysis The clinical resolution rate was evaluated by calculating the ratio between the absolute number of patients with resolution and the overall number of patients who received endoscopic balloon dilation combined with stenting. The recurrence rate was defined as the proportion of the number of patients with recurrence to the number of patients who achieved clinical resolution. The complication and mortality rates were calculated by dividing the number of adverse events and the number of ERCP- and stent-related deaths by the overall number of patients completing endoscopic procedures, respectively. The individual study proportions of outcomes were converted using the Freeman-Tukey double arcsine transformation method before the pooled analysis [18]. The summarized proportions in the original scales were calculated as the back-transformation of the pooled arcsinetransformed pooled estimates. Heterogeneity between studies was evaluated using the I2 statistic. Values less than 25, 50 %, and above 75 % were represented by ‘‘low,’’ ‘‘moderate,’’ and ‘‘high’’ levels of heterogeneity, respectively. If heterogeneity was significant in the studies, a random-effects model was built to calculate the pooled estimate with 95 % confidence intervals (CI) for resolution, recurrence, and complication rates based on the methods of Der Simonian and Laird [19]. In the absence of significant heterogeneity, a fixed-effect model was conducted to combine the outcomes. Studies potentially affecting heterogeneity were then removed from the analyses, and results were compared. Subgroup comparisons between retrospective and prospective studies, as well as between the studies with single and those with multiple stents, were performed using Pearson’s Chi-squared test. Meta-regression analyses were used to explore the potential sources of heterogeneity. Due to power considerations, only univariate mixed effects meta-regression

analysis was performed to investigate the influence of the explanatory factors on the effect size. These factors included study design, year, median or mean time from OLT to BAS diagnosis, median or mean age, male proportion, median or mean number of maximal stents per patient, median or mean stenting duration, and median follow-up period. Funnel plots and Egger’s test were used to investigate publication bias. All statistical analyses were conducted with using RV.2.15.1 (http://cran.r-project.org/).

Results Selection and Characteristics of the Included Studies Figure 1 summarizes the process of identifying eligible clinical studies. The initial search strategy identified 227 citations. After initial title and abstract review, 78 studies were retrieved for detailed review. Based on the aforementioned criteria, 19 studies were included in the final analysis (Table 1). Eight studies were conducted in the USA, four in Italy, and two in the UK. The remaining studies were one in Germany, one in Belgium, one in Argentina, one in the Netherlands, and one in China. All of these were single-center studies. There were 15 Total citations retrieved 227

Irrelevant and duplicate articles 149

Eligible abstracts 78 Case report 8

The Efficacy and Safety of Endoscopic Balloon Dilation Combined with Stenting in Patients with Biliary Anastomotic Strictures After Orthotopic Liver Transplantation.

Endoscopic balloon dilation combined with stenting has been increasingly used in managing biliary anastomotic strictures (BAS) after orthotopic liver ...
2MB Sizes 0 Downloads 37 Views