The influence of the gastrointestinal microbiome on colorectal metastasis: a narrative review.

INTRODUCTION: The gastrointestinal microbiome has been suggested to contribute to the development of both primary and secondary colorectal cancer. Despite advances in understanding the prognostic and predictive value of clinico-pathological parameters, the underlying mechanisms that result in progression to metastatic disease have yet to be defined. The metastatic cascade involves a number of sequential steps, including detachment of tumour cells from the primary site, intravasation and dissemination within the circulatory and lymphatic systems, with extravasation and proliferation at a secondary site. OBJECTIVE: An analysis of the literature relating to the gastrointestinal microbiome and its role in colorectal metastasis was conducted. This review aims to examine the current evidence supporting a role for the microbiome in colorectal metastasis and to describe the mechanisms by which it may contribute to metastatic progression. CONCLUSION: The invasive pathways utilized by bacteria and how they may be manipulated by tumour cells for migration and metastasis are presented and the potential of the intestinal microbiome as a therapeutic target in colorectal carcinogenesis and metastasis is detailed here.

Systematic review of outcomes after total neoadjuvant therapy for locally advanced rectal cancer.

BACKGROUND: Advances in surgical technique and the development of combined-modality therapy have led to significantly improved local control in rectal cancer. Distant failure rates however, remain high, ranging between 20 and 30 per cent. Additional systemic chemotherapy in the preoperative period has been proposed as a means of eradicating subclinical micrometastases and improving long-term survival. The purpose of this systematic review was to evaluate the current evidence regarding induction chemotherapy in combination with standard neoadjuvant chemoradiotherapy, in terms of oncological outcomes, in patients with rectal cancer. METHODS: A systematic review of the literature was performed to evaluate oncological outcomes and survival in patients with rectal cancer who underwent induction chemotherapy and neoadjuvant chemoradiotherapy, followed by surgical resection. Four major databases (PubMed, Embase, Scopus and Cochrane) were searched. The review included all original articles published in English reporting long-term outcomes, specifically survival data, and was limited to prospective studies only. RESULTS: A total of 686 studies were identified. After applying inclusion and exclusion criteria, ten studies involving 648 patients were included. Median follow-up was 53·7 (range 26-80) months. Five-year overall and disease-free survival rates were 74·4 and 65·4 per cent respectively. Weighted mean local recurrence and distant failure rates were 3·5 (range 0-7) and 20·6 (range 5-31) per cent respectively. CONCLUSION: Total neoadjuvant therapy should be considered in patients with high-risk locally advanced rectal cancer owing to improved chemotherapy compliance and disease control. Further prospective studies are required to determine whether this approach translates into improved disease-related survival or increases the proportion of patients suitable for non-operative management.