Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Surgery

Supervisor

Dr. Roberto Hernandez-Alejandro

Abstract

Abstract

Background: Associating liver partition with portal vein ligation for staged-hepatectomy (ALPPS) is a technique for inducing accelerated hypertrophy in patients with insufficient future liver remnant (FLR). It remains unknown whether this hypertrophy may lead to rapid cancer cell dissemination and/or alteration of immune cell/function reconstitution in the FLR. We aimed to determine if the rapid hypertrophy during ALPPS procedure results in more circulating tumour cell (CTCs) dissemination and whether the FLR remains immunologically competent in patients with CRLM.

Methods: In our prospective, observational, 2-arm study, we assessed the utility of CTCs as an evaluation tool for disease dissemination. Moreover, mucosa-associated invariant T (MAIT) cells were used as a marker of liver immune competency of the FLR in patients undergoing to ALPPS (Arm-1) or single stage liver resection (Arm-2; control) from July 2015-June 2016. Blood samples and liver tissue were collected at different time points. CTCs were measured by the CellSearch System. CTC positivity was defined as > 1 CTCs in a 7.5-ml blood sample. Frequency of MAIT cells were measured in both groups (blood, liver and tumour) using flow cytometry.

Results Among 24 potential patients, 17 met the criteria and underwent curative hepatic resection: 7 in Arm-1 and 10 in Arm-2. Baseline demographics were similar between groups. In stage-1 ALPPS, CTCs were present in two patients (28.6%), one of whom continued to be positive after completion of both stages, whereas four patients (44.4%) in Arm-2 were positive, p=0.289. Patients with positive CTCs (one each-Arms) at follow up developed early recurrence and died, p=0.0083. In addition, we found a trend towards an increase in MAIT cells within the liver in Arm-1 compared to Arm-2 (28 %vs17.42%; respectively), (p=0.067), and within the tumor (17.42%vs10.42%, respectively, p=0.308).

Conclusion: Accelerated and extensive liver hypertrophy during ALPPS was not associated with CTC dissemination. Persistent positivity of CTCs at follow-up was significantly associated with disease progression and cancer-related death. Presence and upward trend in the frequency of the MAIT cells in the ALPPS group suggest immune cell restoration in the FLR. Nevertheless, given the small sample size, a larger cohort is needed to validate these findings.

Keywords: Circulating tumor cells (CTCs), Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS), colorectal liver metastases (CRLM), CellSearch System, the mucosa-associated invariant T (MAIT) cells.

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