This Study Will Investigate Whether En Bloc Resection of the Liver and Pancreas with a "non-touch" Technique Followed by Liver Transplantation Will Improve the Overall Survival in Patients with Non-resectable Hilar Cholangiocarcinoma Beyond the Mayo Clinic Transplant Criteria

Last updated: February 28, 2025
Sponsor: Oslo University Hospital
Overall Status: Active - Recruiting

Phase

N/A

Condition

Abdominal Cancer

Digestive System Neoplasms

Liver Cancer

Treatment

Liver transplantation after en bloc resection of the liver and pancreas

Clinical Study ID

NCT06850753
REK743190
  • Ages 18-70
  • All Genders

Study Summary

Surgery for hilar cholangiocarcinoma (phCCA) remains a significant challenge. The minority of patients who are eligible for resection are exposed to high procedure-related morbidity and mortality, and despite apparent R0 resection, cancer recurrence is common. The benefit of R1 resection compared to the best palliative chemotherapy has been questioned. The concept of extended surgery to achieve better radicality is controversial and in many instances, associated with higher procedure-related risk and unclarified oncological benefit. For unresectable patients, liver transplantation, per the Mayo protocol, remains the only alternative for a few patients.

Optimal staging pre- and intraoperatively is problematic since only the local biliary ductal involvement and, to a certain extent, lymph node dissemination can be reasonably correctly assessed. The reliability and validity of the intraoperative frozen section have been questioned. Furthermore, microscopic tumor cell affection leading to recurrent disease has been found in 16% of presumed N0 lymph nodes when analyzed by immunohistochemistry, and patients with nodal micrometastasis showed the same dismal survival as those with positive nodes on regular pathology (pN1).

Taken together, there is a lack of good surgical options for patients with marginally or unresectable phCCA that do not satisfy current criteria for liver transplantation.

The practical problem in the current surgical techniques for hilar cholangiocarcinoma, particularly in locally advanced disease, is that the hepatoduodenal ligament, in most instances, represents an incompletely staged operative field, making the probability of obtaining true free margins uncertain.

An alternative procedure must, therefore, consider the anatomical and multidimensional pattern of dissemination and the limitations in the accurate staging of phCCA, and this suggests that a wider surgical margin is needed to obtain radical resection in locally advanced phCCA.

The aim of the current study is tho these the following hypothesis:

Locally advanced hilar cholangiocarcinoma without M1 lymph node metastatic disease can be radically resected by extending the surgical margin to include the complete hepatobiliary axis and the main anatomical trajectories of local and regional dissemination through an "en-bloc" surgical approach.

M1 metastatic disease is defined as positive nodes in the following locations at staging:

  • Station 9: lymph nodes around the celiac axis.

  • Station 14: lymph nodes along the superior mesenteric artery or vein.

  • Station 15: lymph nodes along the middle colic vein.

  • Station 16: para-aortic lymph nodes.

Patients will be treated by chemotherapy and radiation therapy with an observation period of at least 6 months showing response or stable disease before final inclusion.

The operative procedure consists of a superior right abdominal exenteration, including the liver, pancreas, spleen, and vena cava + liver transplantation. If islets are available from the same donor, this will be administered postoperatively according to the institutional protocol.

Main enpoint is overall survival at 1, 3 and 5 years

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically verified or strong suspicion of cholangiocarcinoma based on radiologyand endoscopy and elevated Ca 19-9 > 100U/L

  • Perihilar cholangiocarcinoma that is deemed unresectable based on tumor location orseverity of the underlying liver disease. Perihilar recurrence in PSC patients morethan 24 months following the previous resection (N0, R0, no macrovascularinvolvement) is accepted.

  • Patients should not be eligible for liver transplantation according to the Mayoprotocol criteria.

  • Tumor involvement of the hepatic artery distal to the gastroduodenal artery or theportal vein without tumor thrombus is accepted.

  • No evidence of distant metastasis or metastatic lymph node (M1) involvement (para-aortic, coeliac or para-colic)

  • Good performance status Eastern Cooperative Oncology Group (ECOG) performance statusscore 0 or 1

  • At least 6 months of observation time during which the patient should be treated bychemotherapy and radiation (hyperfractioned 30-50 Gy) with response or stabledisease before listing for LT. Patients with PSC and significant liver dysfunctionthat restricts the tolerability of chemoradiotherapy may be considered on anindividual basis

Exclusion

Exclusion Criteria:

  • Radiological signs of tumor invasion along intended resection borders

  • Direct tumor invasion of the pancreatic head

  • Signs of spread to the para-aortic, superior mesenteric, or coeliac lymph nodes

  • Perforation of the visceral peritoneum

  • Weight loss >10% in the last six months

  • Patient BMI > 30 kg/m2

  • Other malignancies, except curatively treated basal cell carcinoma or other tumorswith disease-free interval > five years without relapse. The final decision onacceptable previous cancer diagnoses is at the principal investigator's discretion.

  • Known history of human immunodeficiency virus (HIV) infection

  • Substance abuse, medical, psychological, or social conditions that may interferewith the patient's participation in the study or evaluation of the study results

  • Known hypersensitivity to rapamycin

  • Prior metastatic disease

  • Women who are pregnant or breastfeeding

  • Any reason why, in the opinion of the investigator, the patient should notparticipate

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: Liver transplantation after en bloc resection of the liver and pancreas
Phase:
Study Start date:
January 01, 2025
Estimated Completion Date:
December 31, 2030

Connect with a study center

  • Oslo University Hospital

    Oslo, 0424
    Norway

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.