Prospective multi-site study of ultrasound-guided percutaneous biliary drainage and endoscopic ultrasound-guided biliary drainage with implantation of a self-expanding metal stent in patients with malignant, distal bile duct obstruction (PUMa-study)

In a recent systematic review and meta-analysis about the efficacy and safety of endoscopic ultrasound-guided biliary drainage (EUBD) in comparison with percutaneous transhepatic biliary drainage (PTBD), there was no difference in technical success between the two procedures, but PTBD was associated with a lower level of clinical success, a higher level of post-procedural adverse events and a higher rate of re-interventions. The authors concluded that EUBD should be favored for biliary drainage when endoscopic retrograde cholangiopancreaticography (ERCP) failed or wasn´t possible to perform due to anatomical reasons.

The hypothesis of this prospective multicenter study is that PTBD wasn´t performed in an appropriate way to compare it adequately with EUBD. The following improvements should be done. First, color Doppler ultrasound-guidance for cannulating the bile duct should be used in PTBD. The transgression of blood vessels with the risk of severe intrahepatic bleedings or hemobilia can be avoided, which are common adverse events in PTBDs when it is performed by fluoroscopic guidance. Second, the access to the bile duct from the left side of the liver should be favored. The access from the right liver side causes more adverse events such as biliary effusion or pneumothorax, as well as more patient discomfort and pain. Third, implantation of the self-expanding metal stent should be performed in the first session as a one-step procedure. This has the advantage that no further re-intervention is necessary after insertion of an external or an external/internal drainage, an outcome which can cause further adverse events such as bile duct leak along the catheter, biliary ascites or catheter dislocation. Fourth, stent release should be performed under endoscopic luminal guidance. In this way, the positioning and the correct expansion of the distal tip of the metal stent can be observed directly in comparison with the stent release which is only controlled by fluoroscopic guidance.

On the other hand, EUBD should be performed in its best manner (special metal stents included) with the three techniques that are usually necessary to perform a successful EUBD: EUS-guided antegrade transpapillary drainage, EUS-guided transhepatic drainage and EUS-guided choledochal drainage.

The study focuses on patients with malignant distal (infra-hilar) bile duct obstruction.

It is presumed that the technical and clinical success rate is equal (non-inferiority) but the adverse event rate, the number of re-interventions and the number of days of hospitalization may differ between the two interventions. An adequate number of cases (106 patients in each intervention, drop outs included) should be recruited to calculate relevant statistical differences.

Furthermore, patients will be followed over six months after the intervention to calculate an estimated survival analysis (with and without palliative chemotherapy).

Inclusion Criteria:

• Inoperable, malignant disease with extrahepatic bile duct obstruction (infra- hilar)
• ERCP was not successful or wasn´t possible due to anatomical reasons (for example status post-gastrectomy)
• At least twofold elevated bilirubin level (> 2mg/dl)
• Histologically verified malignant disease
• Abdominal ultrasound was performed
• Computed tomography or magnetic resonance imaging of the abdomen was performed
• A written consent was given

Exclusion Criteria:

• Relevant blood coagulation disorder (Quick < 50%, Partial thromboplastin time > 50 sec., thrombocytes < 50/nl)
• Extrahepatic cholangiocellular carcinoma (Klatskin tumor) Bismuth II-IV or intrahepatic cholangiocellular carcinoma
• Operable, malignant disease or disease which can be cured by chemotherapy (for example aggressive Non Hodgkin-lymphoma)
• Pregnancy or breastfeeding
• Participation in another trial concerning PTBD or EUBD