Limitations in resectability of colorectal liver metastases 2020 - A systematic approach for clinicians and patients.

Colorectal liver metastases (CRLM) affect over 50 % of all patients with colorectal cancer, which is the second leading cause of cancer in the western world. Resection of CRLM may provide cure and improves survival over chemotherapy alone. However, resectability of CLRM has to be decided in multidisciplinary tumor boards and is based on oncological factors, technical factors and patient factors. The advances of chemotherapy lead to the abolition of contraindications to resection in favor of technical resectability, but somatic mutations and molecular subtyping may improve selection of patients for resection in the future. Technical factors center around anatomy of the lesions, volume of the remnant liver and quality of the liver parenchymal. Multiple strategies have been developed to overcome volume limitations and they are reviewed here. The least investigated topic is how to select the right patients among an elderly and frail patient population for the large variety of technical options specifically for bi-lobar CRLM to keep 90-day mortality as low as possible. The review is an overview over the current state-of-the art and a systematic guide to the topic of resectability of CRLM for both clinicians and patients.

Debulking Hepatectomy for Colorectal Liver Metastasis Conveys Survival Benefit.

(1) Background: Despite advances in surgical technique and systemic chemotherapy, some patients with multifocal, bilobar colorectal liver metastases (CRLM) remain unresectable. These patients may benefit from surgical debulking of liver tumors in combination with chemotherapy compared to chemotherapy alone. (2) Methods: A retrospective study including patients evaluated for curative intent resection of CRLM was performed. Patients were divided into three groups: those who underwent liver resection with recurrence within 6 months (subtotal debulked, SD), those who had the first stage only of a two-stage hepatectomy (partially debulked, PD), and those never debulked (ND). Kaplan-Meier survival curves and log-rank test were performed to assess the median survival of each group. (3) Results: 174 patients underwent liver resection, and 34 patients recurred within 6 months. Of the patients planned for two-stage hepatectomy, 35 underwent the first stage only. Thirty-two patients were never resected. Median survival of the SD, PD, and ND groups was 31 months, 31 months, and 19.5 months, respectively (p = 0.012); (4) Conclusions: Patients who underwent a debulking of CRLM demonstrated a survival benefit compared to patients who did not undergo any surgical resection. This study provides support for the evaluation of intentional debulking versus palliative chemotherapy alone in a randomized trial.

A Retrospective Study on the Role of Metformin in Colorectal Cancer Liver Metastases.

Colorectal cancer liver metastases (CRCLMs) have two main histopathological growth patterns (HPGs): desmoplastic (DHGP) and replacement (RHGP). The vascularization in DHGP tumours is angiogenic, while the RHGP tumours exert vessel co-option vasculature. The presence of vessel co-option tumours is associated with poor response to anti-angiogenic agents and chemotherapy, as well as a worse prognosis. Metformin has been shown to influence the progression and vasculature of tumours in different cancers. However, its role in CRCLM is poorly understood. Herein, we conducted a retrospective cohort study to examine the role of metformin in CRCLM. A dataset of 108 patients was screened, of which 20 patients used metformin. The metformin user patients did not use metformin as an anticancer agent. We noticed a significantly lower percentage of CRCLM patients with vessel co-opting RHGP tumours in the population that used metformin compared to CRCLM patients who did not use metformin. Similar results were obtained when we compared the ratio of recurrence and extrahepatic metastases incidence. Moreover, the metformin user patients had significantly higher survival outcome compared to nonusers. Collectively, our data suggest that metformin administration is likely associated with better prognosis of CRCLM.

Targeting Liver Metastases to Potentiate Immunotherapy in MS-Stable Colorectal Cancer-A Review of the Literature.

Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective for 95% of patients with microsatellite-stable disease. Recent evidence suggests that the liver's immune microenvironment plays a pivotal role in limiting the effectiveness of immunotherapy. There is also evidence to show that targeting liver metastases with locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy for these patients. This review presents evidence from preclinical studies regarding the underlying mechanisms and from clinical studies that support this approach. Furthermore, we outline potential directions for future clinical trials. This innovative strategy could potentially establish immunotherapy as an effective treatment for MS-stable colorectal cancer patients, which are currently considered resistant.