Preventive transhepatic tract embolisation (PTTE) after percutaneous biliary intervention (PBI) may reduce adverse events. The aim of this systematic review was to analyse feasibility, safety, and efficacy of PTTE with different embolic agents. A systematic literature research was performed according to the PRISMA guidelines. The identified studies were analysed concerning study quality, number of cases, indication, embolic agent, embolisation technique, success, and embolisation-related adverse events. Out of 62 identified records, 7 studies of mainly moderate study quality published through 2019 were included for further analysis. Cyanoacrylate (
Percutaneous biliary intervention (PBI) can be associated with high rates of different adverse events [
Case example with fluoroscopy images of a patient with hemihepatectomy for cholangiocellular carcinoma who received PTTE with gelatin foam after percutaneous transhepatic balloon dilation of a stenosis of the hepaticojejunal anastomosis (Department of Diagnostic and Interventional Radiology of University Hospital of Heidelberg). (a) The 6 F-sheath is withdrawn from a dilated biliary duct (black arrow) by continuous injection of a contrast agent. (b) Injection of gelatin foam through a side port of the sheath into the transhepatic tract (black brackets). (c) Detachment of gelfoam (white arrow) from the sheath tip marks the liver capsule.
This systematic review was performed in accordance with the PRISMA guidelines [
An experienced medical librarian (V. B.) developed the search strategy and performed the literature search. PubMed, Embase, and Cochrane database were searched using a search strategy developed to identify all papers on embolisation in association with PBI regardless of study design. The following search terms were used: “Percutaneous Biliary Intervention,” “Embolization, Therapeutic,” “Embolotherapy,” “Embolization,” “Closure” and “Liver,” “Liver Tract,” “Transhepatic Tract,” “Bile Duct,” “Biliary Duct.” The search included all articles published through 16 May 2019. All results were downloaded into EndNote X9 (Clarivate Analytics, Boston, USA), a bibliographic database manager. To further increase our possible search results, we manually searched articles through the references of the retrieved publications. Based on the title and abstract, we selected articles for full-text review. Duplicate publications and articles not published in English or German were removed.
The following criteria were defined as inclusion criteria: comparative and noncomparative studies concerning preventive liver tract embolisation after PBI using any kind of embolic agent should be included. Case reports or case series less than 3 cases on preventive transhepatic tract embolisation as well as studies on percutaneous therapeutic bile duct embolisation in biliary leak should be excluded as the aim of this study was preventive embolisation. Studies had to report at least 1 of the following: technical success which was defined as successful closure of the transhepatic tract proven by injected contrast medium during fluoroscopy; clinical success which was defined as a reduction of PBI-associated adverse events in comparison with a control group without preventive transhepatic tract embolisation, or embolisation-related adverse events.
Two reviewers (DS, DC) independently assessed the eligibility and validity of each study as well as the extracted data. Extracted data included study design, year of the study, number of cases, indications for PBI, the embolic agent used, the technique of embolisation, technical as well as clinical success of embolisation, PBI-associated adverse events, and embolisation-related adverse events. Embolisation-related adverse events were retrospectively classified according to the CIRSE classification system of complications in interventional radiology [
For study quality assessment, we used the Newcastle-Ottawa scale (NOS) [
Fifty-nine records were identified through database searching, and 5 additional records were identified through other sources. After having removed all duplicated records, all 62 search results were screened. Fifty-five records concerning liver tract embolisation after liver biopsy (
Screening and inclusion process are shown in a flow diagram according to the PRISMA statement (
All 7 studies were single center based. A total of 314 patients with embolisation were included in the analysis. Meta-analysis was not performed since only two studies had controls without embolisation comprising a further 123 patients.
Based on the Newcastle-Ottawa scale assessment, 1 study was of high quality [
Summary of critical appraisals of included studies using the Newcastle-Ottawa quality assessment scale.
Selection | Comparability | Outcome | Study quality (number of stars) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Embolic agent | Study | Representativeness of the intervention group | Selection of nonintervention group | Documentation of intervention | Outcome is not present at the beginning of the study | Most important endpoint | Additional endpoints | Assessment of outcome | Follow-up long enough | Follow-up complete | |
Cyanoacrylate | Schmitz-R 2000 |
|
|
|
|
|
|
Moderate (6) | |||
Lyon 2006 |
|
|
|
|
|
|
|
Moderate (7) | |||
Seif 2013 |
|
|
|
|
|
|
Moderate (6) | ||||
Hwang 2019 |
|
|
|
|
|
Moderate (5) | |||||
Gelatin | Dale 2015 |
|
|
|
|
|
|
|
|
High (8) | |
Augustin 2019 |
|
|
|
|
|
Moderate (5) | |||||
Coils | Sofue 2012 |
|
|
|
|
Low (4) |
The indication for PBI was mainly malign bile duct obstruction (not always specified) in all studies with 252/314 (80.3%, range: 61.9–100%). Patients with malign bile duct obstruction were mixed with patients with an underlying benign disease such as bile duct stones in 5 of 7 studies [
Cyanoacrylate followed by
Overall, the technical success of embolisation was very high in all studies with 99.0 (96.0–100%).
Adverse events related to embolisation were rare (10/314 (3.2%)) and were exclusively observed in two patients with glue migration after cyanoacrylate embolisation. In one patient, a small amount of fragmented glue was detected by a CT scan outside the biliary stent but did not cause any symptoms [
In the two studies with patients with malign ascites, embolisation was combined with the insertion of a self-expandable metal stent as a one step-procedure [
Techniques of preventive transhepatic tract embolisation, technical success, and embolisation-related adverse events graded according to the CIRSE classification.
Embolic agent | Author/year | Technique of transhepatic tract embolisation | Technical success (%) | Embolisation-related adverse events (%) |
---|---|---|---|---|
Cyanoacrylate | Schmitz-R 2000 | NBCA and iodised oil (50 : 50); injected through a 3F-PTFE-catheter; 7F-or 9F-port | 20/20 (100.0%) | 0/20 (0.0%) |
Lyon 2006 | NBCA and iodised oil (50 : 50); injected through an 8F-dilator catheter | 21/21 (100.0%) | 0/20 (0.0%) | |
Seif 2013 | NBCA and iodised oil (80 : 20); injected through a 6F-dilator catheter | 24/25 (96.0%) | Glue migration: CIRSE 3°: 1/25 (4.0%) | |
Hwang 2019 | NBCA/iodised oil (50 : 50; 40 : 60; 33 : 66), autologous blood, injected through an 8/14F-dilator catheter | 41/42 (97.6%) | 1/42 (2.4%) glue migration: CIRSE 1°, pain: 8/42 (19.0%) | |
Gelatin | Dale 2015 | Gelatin foam pledgets, 14G/2 cm length, 2-3, one with radiopaque marker, push rod stylet, 8F-port | 92/92 (100.0%) | 0/92 (0.0%) |
Augustin 2019 | Gelatin sponge torpedoes, manually prepared, delivered by pushing catheter/flushing, 8/11F-port | 97/98 (98.9%) | 0/98 (0.0%) | |
Coils | Sofue 2012 | Metallic coils: 1–3 (5 mm × 5 cm; 4 mm × 3 cm; 3 mm × 4 cm); 6.5F-port | 16/16 (100.0%) | 0/16 (0.0%) |
All | 311/314 (99.0%) | 10/314 (3.2%) |
Clinical efficacy of PTTE could be assessed in two studies with controls without embolisation [
PBI-related adverse events after percutaneous biliary intervention, preventable by transhepatic tract embolisation or not. The follow-up period in days (median).
Embolic agent | Author/year | Follow-up (days) | Biliary leak | Liver tract bleeding | PBI-related pain | Adverse events not preventable by tract embolisation |
---|---|---|---|---|---|---|
Cyanoacrylate | Schmitz-R 2000 | 95 | 1/20 (5.0%) | 0/20 (0.0%) | Not tested | 1/20 (5.0%): tract metastasis after 30 days |
Lyon 2006 | 1 | Not reported | Not reported | 6/21 (28.6%) | 3/21 (14.3%): biliary sepsis (2), haemobilia (1) | |
Seif 2013 | 182 | 2/25 (8.0%) | 0/25 (0.0%) | 11/25 (44.0%) | 4/25 (16.0%): cholangitis | |
Hwang 2019 | 58 | 1/42 (2.4%) | 0/42 (0.0%) | Not tested | Not reported | |
Gelatin | Dale 2015 | 10 | Not reported | 1/92 (1.9%) | Not tested | Not reported |
Augustin 2019 | 361 | 3/98 (3.1%) | 0/98 (0.0%) | Not tested | 7/98 (7.1%): cholangitis (5), arterial haemorrhage (1), tract metastasis (1) after 12 months | |
Coils | Sofue 2012 | 66 | 0/16 (0.0%) | 0/16 (0.0%) | Not tested | 8/16 (50.0%): pleural effusion (4), cholangitis (2), haemobilia (2) |
All | 7/201 (3.5%) | 1/293 (0.3%) | 17/46 (36.9%) | 23/180 (12.8%) |
Furthermore, adverse events that probably could not have been prevented by PTTE such as cholangitis, 2 tract metastasis after 30 days and 12 months, arterial intrahepatic haemorrhage, haemobilia, and nonbiliary pleural effusion were observed in 23/180 (12.8%) patients. As mentioned above, PBI-related pain was quantified in only two studies [
Preventive liver tract embolisation after PBIs was technically successful in almost all patients, and embolisation-related adverse events were rare. These review results suggest that PTTE is feasible and safe. However, the efficacy of PTTE cannot be clearly assessed on the basis of the present seven studies as only two of them had a control group without embolisation.
The only one prospective randomised study with a short follow-up of a few days using cyanoacrylate as an embolic agent showed a significant reduction of PBI-related pain. It did not report in which group other important adverse events as haemorrhage or biliary leak occurred [
The second controlled study, which was a retrospective before-after study focussing on haemorrhage as an adverse event, showed a significant reduction of bleeding complications from 12.0% to 3.0% when the number of blood transfusions was combined with the number of visualised bleeding events by imaging methods [
An effect of PTTE on biliary leak was not proven by any of the 7 studies as it was not tested, or negative control was lacking. Therefore, the true effect of PTTE on biliary leak still needs to be proven. However, the cumulative incidence of biliary leaks was quite low with 7/201 (3.5%) cases. Comparison with historical study data concerning biliary leak is difficult as multiple variables may influence the incidence of the biliary leak in PBIs such as by a remaining external catheter. However, a recent meta-analysis on PBI versus EUS-guided biliary drainage found an incidence of 30/151 (19.8%) biliary leaks in PBI without PTTE [
Adverse events that might be not preventable by transhepatic tract embolisation such as cholangitis or biliary sepsis, arterial intrahepatic haemorrhage, nonbiliary pleural effusion, or tract metastasis occurred in 23/180 (12.8%) of documented patients. These adverse events show the possible limitation of PTTE on the one side and the necessity of an adequate follow-up period on the other side as two of the tract metastases were observed several months after PBI.
Cyanoacrylate is successfully used in interventional radiology and gastrointestinal endoscopy for a long time and dedicated applications are commonly available. However, glue migration as an adverse event was reported in two studies. In one patient, the occluded biliary metal stent had to be reopened by the insertion of an angioplasty balloon catheter. Although cyanoacrylate-related adverse events were rare and without relevant severe consequences, it has to be kept in mind that cyanoacrylate glue deposition is inherently not always predictable, and nontarget embolisation, venous migration, microcatheter blockage, and catheter retention might occur [
Manually prepared gelatin torpedoes or gelatin pledgets approved for liver tract sealing after liver biopsy were applied in two retrospective, uncontrolled cohort studies [
The one available study on PTTE with coils showed no bile leak and no transhepatic tract bleeding in 16 patients with malign ascites although bile fluid or bleeding was not routinely ruled out by paracentesis [
The significance of this review is weakened by the few available studies (
A prospective, randomised (multicentre) study should be performed that examines all three likely relevant adverse events such as haemorrhage, biliary leak, and pain (quantified pain score). This study should have an adequate case number to show a significant impact of PTTE on PBI-related adverse events. Keeping in mind reported incidences of haemorrhage (without haemobilia) and biliary leak in PBI with PTTE in this review of 0.3% and 3.5%, respectively, compared with the reported data on PBI without PTTE of 3.3% and 19.8%, respectively, in the abovementioned meta-analysis [
PTTE is feasible and safe. It is effective concerning the prevention of PBI-related pain, and it may be effective concerning haemorrhage. The prevention of biliary leak is not proven. It remains unclear which embolic agent should be preferred. A prospective randomised trial including all preventable adverse events is lacking.
All available data are included in the manuscript.
Svetlana Hetjens and Matthias P. A. Ebert share the last authorship.
The authors declare that they have no conflicts of interest.
The authors would like to thank the medical librarian Volker Braun from the Library of Mannheim University Hospital (Germany) for conducting the literature search.