Primary percutaneous placement of metal stents for palliative biliary drainage in patients with a primary malignant perihilar stricture

Rationale: Most patients with perihilar cholangiocarcinoma (pCCA) are ineligible for curative-intent resection because of metastatic disease, locally advanced disease, or due to comorbidity. The key to successful palliative treatment is adequate biliary drainage to improve the patient’s wellbeing and to allow for palliative systemic therapy. Endoscopic biliary drainage with plastic stents is the most common technique in the Netherlands. The main problem of this approach is that the stents cause bacterial colonization of the previously sterile intrahepatic bile ducts, because the stents cross the ampulla. Cholangitis often develops, especially if undrained segments become colonized. This is reflected by a 35% mortality within 3 months after diagnosis in patients who are ineligible for curative-intent resection. Most of these patients die from biliary obstruction and cholangitis without known metastatic disease. The only method to avoid colonization of the bile ducts is percutaneous placement of uncovered self-expandable metal stents (SEMS) that do not cross the ampulla.

Objective: To proof safety and feasibility of direct percutaneous SEMS placement for palliative treatment of primary malignant perihilar stricture.
Study design: In preparation of the design of a phase-II study, we aim to perform a proof-of-concept pilot study at Erasmus MC, including 10 patients. The expected inclusion period is 1 year.

Study population: Patients with unresectable primary malignant perihilar obstruction on imaging with histopathological confirmation or high clinical suspicion (as determined by the multidisciplinary hepatobiliary team) who did not undergo previous endoscopic or percutaneous drainage procedures and who have no signs of cholangitis.

Intervention: Percutaneous transhepatic biliary drainage, by bridging significant ductal obstruction by self-expandable fenestrated metal stents without cannulation of the ampulla.

Main study parameters/endpoints: Stent-related complications according to Clavien-Dindo grading system within 90 days (see Table 1.), absolute and relative (%) bilirubin decrease after 14 days and number of scheduled and unscheduled reinterventions within 90 days.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The percutaneous intervention is an alternative approach to the standard of care, which is endoscopic biliary drainage. Complications due to the transhepatic biliary drainage, i.e. bleeding, infection and bile leakage are uncommon (<5%).
We hypothesize that direct SEMS placement in patients with unresectable primary malignant perihilar obstruction minimizes post-drainage cholangitis and mortality, requires fewer reinterventions, and increases the rate of patients receiving palliative chemotherapy.
In this study, patients will undergo an invasive procedure with hospital discharge on the same day. This corresponds to the standard of care. Follow-up appointments are planned 14 days (T1), one month (T2) and three months (T3) after stent placement. These visits will take 30 minutes. T2 and T3 are extra visits compared to standard of care.

We hypothesize that direct SEMS placement in patients with unresectable primary malignant perihilar obstruction minimizes post-drainage cholangitis and mortality, requires fewer reinterventions, and increases the rate of patients receiving palliative chemotherapy.

Follow-up appointments are planned as deemed necessary by the treating specialist, but at least 14 days (T1), one month (T2) and three months (T3) after stent placement. Each follow-up will take 30 minutes. During T1, two blood samples (20 ml in total) will be taken. This corresponds to the standard of care. During the other visits blood samples will only be taken by discretion of the treating physician. If patients returned to their referring hospital or if visits are too stressfull, the T2 and T3 visits will be telephone calls. During these calls patients will answer questions about the presence of fever, jaundice and abdominal pain. 1 year after inclusion the treating physician will be contacted about late complications and vital status.

Preprocedural intravenous antibiotic prophylaxis is administered (cefuroxime 1500 mg/metronidazole 500 mg; conform institutional ERCP protocol). An interventional radiologist performs the percutaneous transhepatic biliary drainage, by bridging significant ductal strictures by self-expandable fenestrated metal stents without cannulation of the ampulla. Bile cultures are routinely taken. The tract is sealed with glue without leaving an external drain. When histological confirmation is lacking (on estimation about one third of all patients with primarily unresectable pCCA) during the same procedure percutaneous biopsies and brush cytology are taken to confirm the presence of pCCA by frozen section before SEMS-placement, to prevent the placement of non-removable SEMS in patients with non-malignant disease.
The radiologist reports whether stent placement was technically successful, the difficulty of the procedure (scale 1-10) and whether a second drainage procedure is indicated (e.g., in case the stricture cannot be passed in the first attempt). Technical success is defined as successful passage of the stricture. Successful drainage is defined as a bilirubin below 50 mmol/l or a reduction in bilirubin level of at least 50% within 14 days after drainage.