The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer

529 Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.

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Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

Cancers ◽

10.3390/cancers13102418 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2418

Author(s):

Xuezhen Zeng ◽

Simon E. Ward ◽

Jingying Zhou ◽

Alfred S. L. Cheng

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Cancer Patients ◽

High Recurrence Rate ◽

Immune Microenvironment ◽

Liver Sinusoidal Endothelial Cells ◽

Premetastatic Niche ◽

Cancer Pathogenesis ◽

Colorectal Cancer Patients ◽

The Impact

A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.

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Coadjuvant Anti-VEGF A Therapy Improves Survival in Patients with Colorectal Cancer with Liver Metastasis: A Systematic Review

Gastrointestinal Disorders ◽

10.3390/gidisord2020007 ◽

2020 ◽

Vol 2 (2) ◽

pp. 71-85

Author(s):

Isabel Novo ◽

Bárbara Campos ◽

Filipa Pinto-Ribeiro ◽

Sandra F. Martins

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Liver Metastasis ◽

Survival Rates ◽

Progression Free Survival ◽

Vascular Endothelial ◽

Inclusion Criteria ◽

Effective Treatment Modality ◽

Endothelial Growth Factor ◽

The Impact

Background: the presence of liver metastasis in colorectal cancer (CRC) remains one of the most significant prognostic factors. Objective: systematically review the results of studies evaluating the benefit of adding bevacizumab to a normal chemotherapy regime in the survival of patients with colorectal-cancer liver metastasis (CRLM). Search methods: Pubmed and Google Scholar databases were searched for eligible articles (from inception up to the 2 April 2019). Inclusion criteria: studies including patients with CRLM receiving anti-vascular endothelial growth factor (VEGF; bevacizumab) as treatment, overall survival as an outcome; regarding language restrictions, only articles in English were accepted. Main results: Eleven studies met the inclusion criteria. In 73% of these cases, chemotherapy with bevacizumab was an effective treatment modality for treating CRLM, and its administration significantly extended both overall survival (OS) and/or progression-free survival (PFS). Nevertheless, three articles showed no influence on survival rates of bevacizumab-associated chemotherapy. Author conclusions: It is necessary to standardize methodologies that aim to evaluate the impact of bevacizumab administration on the survival of patients with CRLM. Furthermore, follow-up time and the cause of a patient’s death should be recorded, specified, and cleared in order to better calculate the survival rate and provide a comparison between the produced literature.

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The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

International Journal of Molecular Sciences ◽

10.3390/ijms19123711 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3711 ◽

Cited By ~ 22

Author(s):

Ovidiu Balacescu ◽

Daniel Sur ◽

Calin Cainap ◽

Simona Visan ◽

Daniel Cruceriu ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Cancer Progression ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Cancer Management ◽

Incidence And Mortality ◽

The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.

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The impact of laparoscopic surgery in colorectal cancer resection with respect to the development of liver metastasis in the long-term

Journal of Coloproctology ◽

10.1016/j.jcol.2015.12.002 ◽

2016 ◽

Vol 36 (1) ◽

pp. 8-15 ◽

Cited By ~ 1

Author(s):

Renata Rostirolla ◽

Paulo Fontes ◽

Mauro Pinho ◽

Miguel Pedroso ◽

Tatiana Masuko ◽

...

Keyword(s):

Colorectal Cancer ◽

Laparoscopic Surgery ◽

Liver Metastasis ◽

Cancer Resection ◽

Colorectal Cancer Resection ◽

The Impact

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The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases

10.20944/preprints201810.0659.v1 ◽

2018 ◽

Author(s):

Ovidiu Balacescu ◽

Daniel Sur ◽

Calin Cainap ◽

Simona Visan ◽

Daniel Cruceriu ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Beta Catenin ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Cancer Management ◽

Incidence And Mortality ◽

The Impact

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis, published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial-mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.  

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