Liver Transplantation for Cholangiocarcinoma: An Effective Therapy
Our hypothesis is that select patients undergoing liver transplantation for CCA, in the context of multi-modality neoadjuvant therapy, exhibit survival equivalent to other established indications for liver transplantation as previously demonstrated31. We will also attempt to extend previously published criteria for liver transplantation in the setting of CCA by offering this protocol to patients with evidence of intrahepatic disease and regional nodal disease. Patients undergoing transplantation for CCA will be followed longitudinally for their entire post-transplant course, and compared with a matched cohort of liver transplant recipients in regard to post-transplant survival, survival on the waiting list, as well as complications pre-and post-transplantation. Explanted livers will be examined for the presence of residual tumor.
We will investigate the additional hypothesis that a sequence of events occurs in the biliary epithelium as it progresses from normal histology, to PSC, to CCA, akin to the polyp-cancer sequence described in certain types of colorectal cancer32. Accordingly, we will examine resection specimens from patients undergoing liver resection for non-biliary tract malignancy; PSC patients undergoing diagnostic brushings, biliary aspirates, or biopsy; and liver biopsies obtained at operation in patients with inflammatory bowel disease. These will be compared to patients enrolled in the liver transplant protocol (see below) with a known, biopsy-proven diagnosis of cholangiocarcinoma. Finally, to study the effects of chronic bile exposure on the biliary epithelium, gene expression in the proximal biliary tree will be compared to more distal segments in those resection specimens obtained from patients with non-biliary tract malignancies.
- Participants must be 16 years or older
- Study will include four groups of participants
- Subjects without cholangiocarcinoma that are NOT undergoing the liver transplant protocol will complete a different consent form from those in the liver transplant protocol. The protocol and consent for obtaining tissue in these subjects will be under the umbrella of IRB_00019568. We summarize both parts of the study in this protocol such that the reviewer can understand how each piece fits into the whole study schema.
- Patients harboring a diagnosis of PSC without evidence of malignancy will be enrolled as control patients for the comparison of immunohistochemistry and microarray data from their biliary aspirates or from biopsies performed for diagnostic purposes.
- A third group of patients will be enrolled who are undergoing liver resection for non-biliary tract malignancies (i.e. colorectal metastases).
- Additional patients will be enrolled who have been diagnosed with inflammatory bowel disease (Crohn's disease and ulcerative colitis), who will undergo surgical intervention for resection of diseased bowel, or who will undergo creation of ileal-anal pouch procedures.
- Patients are eligible for the protocol once they have attained their sixteenth birthday. Patients will be excluded for medical co-morbidities that would preclude the use of general anesthesia. Pregnant patients and those patients hoping to become pregnant will not be eligible for the study.
Guidelines for Ineligibility:
- Patients with metastatic disease are not eligible for this trial. **
- Patients who have previously undergone chemotherapy or radiotherapy.
- Patients with an uncontrolled infection.
- Patients with a previous malignance other than non-melanoma skin cancer or in situ cervical cancer within the last five years.
- Patients with medical conditions precluding transplantation.
- Patients with metastatic disease (including N2 disease).
- Patients with hilar tumors extending below the cystic duct
Liver Transplant Protocol:
- The surgical protocol will initially be offered to liver transplant candidates with de novo hilar CCA or CCA arising in the setting of PSC.
- Diagnosis of CCA will be established by intraluminal brush cytology, intraluminal biopsy, or a carcinoma antigen (CA) 19.9 level greater than 100 ng / mL in the setting of a radiographic malignant stricture.
- Biliary aneuploidy demonstrated with DIA and FISH will be considered equivalent to cytology.
- All patients with CCA will be evaluated by the liver transplant team which includes experienced hepatobiliary and liver transplant surgeons.
- Patients will be presented at the weekly liver transplant selection conference to assess their candidacy, as well as the weekly GI Multidisciplinary Tumor Conference at the Huntsman Cancer Institute. Clinical staging prior to neoadjuvant therapy will include chest and abdominal computed tomography, liver ultrasound, and bone scan. Patients will also undergo endoscopic ultrasound with fine needle aspiration of suspicious lymph nodes.
- All patients will undergo staging laparoscopy to rule out the presence of peritoneal disease followed by staging laparotomy.
- Patients with N1 disease (metastasis to lymph nodes within hepatoduodenal ligament) will remain eligible for the protocol.
- Tumor size will not be included in the exclusion criteria. Patients with evidence of disease progression beyond study criteria will not be eligible to continue on to liver transplantation.
How long does it run?
Trials will run until March 2010
Location(s) of clinical trial
University of Utah/Huntsman Cancer Institute
Salt Lake City, Utah, United States, 8411
Status: Open Enrollment
Name, Phone, Email
Contact: Diane Gardner 801-585-0431 email@example.com
Contact: Jenny Hatch 801-585-3098 firstname.lastname@example.org
Principal Investigator: Jason Schwartz, M.D., University of Utah
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