Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

O-L01 Learning curve for laparoscopic liver resection: does it affect survival in colorectal liver metastasis?

Background After Gagner introduced laparoscopic liver resection (LLR) in 1992, it was not until 2004 that the first series with more than ten laparoscopic major liver resections was reported. Furthermore, a multicentre study by Allard et al., in 2015 revealed that laparoscopy was only used in 176 (6.7%) patients out of a total of 2620 patients treated for colorectal liver metastasis (CRLM). This lag time in the establishment of LLR was attributed to the steep learning curve (LC) due to technical complexity and caution about oncological safety. The aim of this study is to assess if the learning curve of LLR has affected survival of patients with CRLM. Methods All consecutive LLR performed by a single surgeon between 2000–2019 were retrospectively analysed. RA-CUSUM for conversion rate and the log regression analysis of the blood loss were used to identify two phases in the learning curve. LC was then applied to CRLM patients and the two subgroups were compared for oncological and survival outcomes. The analysis was repeated with propensity score-matched (PSM) groups Results A total of 286 patients were included in the learning curve analysis. Combining the results from the RA-CUSUM and the blood loss log curve identified two distinct phases in the learning curve. The early phase (EP, n = 68) represented the initial learning experience, and the late phase (LP, n = 218) represented increased competence and the introduction of more challenging cases. The LC was applied to 192 patients with colorectal liver metastasis (EPc n = 45, LPc n = 147). R0 resection was achieved in 93%; 100% in EPc and 90% in LPc (P = .02). The cohort median overall survival (OS) and was 60 months. The median recurrence-free survival (RFS) was 16 months. The 5- year OS and RFS were 51% and 33%, respectively. The overall and recurrence-free survival rates were not compromised by the learning curve; OS (HR: 0.78, 95% CI 0.51-1.2, p = .26), RFS (HR: 0.94, 95 % CI 0.64-1.37, p=.76). Results were replicated after PSM. Conclusions In our experience, the development of a laparoscopic liver resection program can be achieved without adverse effect on the long-term survival in CRLM.

Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.

Systematic Review Comparing the Effectiveness of Robotic verse Laparoscopic Liver Surgery in Colorectal Liver Metastasis (CRLM)

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world. The liver is the most common site of metastasis with 15 to 25% of patients presenting with synchronous colorectal liver metastasis (CRLM). This study is aimed at evaluating the long- and short-term outcomes of laparoscopic and robotic CRLM surgery, and directly comparing their respective effectiveness. Methodology: A literature search was performed and all studies that reported on operative characteristics, oncological outcomes for CRLM, morbidity or mortality and cost-effectiveness on robotic or laparoscopic surgery were included. The study design was in keeping with the PRISMA guidelines. Results: From the initial 606 manuscripts identified, 19 studies were included in the final qualitative analysis. A total of 1340 patients with 1194 LLR (Laparoscopic Liver Resection) and 146 RLR (Robotic Liver Resection) cases were analysed. Within the LLR group, the average tumour size excised was 32.1 mm compared to the RLR group of 33.8 mm. The average operative time in the LLR was 193 min, CI of 95% (147.4 min to 238.6 min) compared to RLR 257 min, CI of 95% (201.5 min to 313.8 min) with a p-value < 0.0001. Estimated blood loss was lower in the RLR group (210 mL) compared with the LLR group (246 mL). Conclusion: Despite the higher operative cost, RLRs do not result in statistically better treatment outcomes, with the exception of lower estimated blood loss and excision of larger CRLMs. Operative time and total complication rate are significantly more favourable with LLRs. Our study has shown that robotic liver surgery is safe and feasible in well-selected patients.