Translational Study of Liver Cancer and Hypertrophy: TranSLiCH

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 \u3e 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

Patient survival after simultaneous ALPPS and colorectal resection

BACKGROUND: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. METHODS: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. RESULTS: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. CONCLUSIONS: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score: is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?

Background Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively. Methods Thirteen high-volume centers participated in this retrospective multicentric study. A risk analysis based on patient characteristics, underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score. A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index (CCI), the age-adjusted CCI (aCCI), the ALPPS risk score before Stage 1 (ALPPS-RS1) and Stage 2 (ALPPS-RS2). The model was internally validated applying bootstrapping. Results A total of 451 patients were included. Mortality was 14.4%. The CAPRA score is calculated based on the following formula: (0.1 × age) - (2 × BSA) + 1 (in the presence of primary liver tumor) + 1 (in the presence of severe cardiovascular disease) + 2 (in the presence of moderate or severe diabetes) + 2 (in the presence of renal disease) + 2 (if classic ALPPS is planned). The predictive ability was 0.837 for the CAPRA score, 0.443 for CCI, 0.519 for aCCI, 0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2. After 1,000 cycles of bootstrapping the C statistic was 0.793. The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70. Conclusions Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure. By assessing the patient's preoperative condition in relation to ALPPS, the CAPRA score has a very good ability to predict postoperative mortality