Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study

Chiou, Wen‐Yen; Chang, Chun Ming; Tseng, Kuo‐Chih; Hung, Shih‐Kai; Lin, Hsing Ying; Chen, Yi Chun; Su, Yu Chieh; Tseng, Chih‐Wei; Tsai, Shiang Jiun; Lee, Moon Sing; Li, Chung‐Yi

doi:10.1093/jjco/hyu178

Cited by 21 publications

(21 citation statements)

References 26 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although liver metastasis can occur in CRC patients without NAFLD, a recent large prospective human cohort analyzing 2,715 CRC patients with liver metastasis as well as other retrospective studies have suggested that the patients with NAFLD have an increased risk of liver metastasis and for the recurrence of liver metastasis after resection, when compared with patients without NAFLD . Moreover, higher recurrence rate of liver metastasis in patients with fibrosis have also been reported in recent studies . However, previous studies underestimated the risk of liver metastasis or have reported contradictory results in patients with underlying fatty liver and fibrosis .…”

Section: Discussionmentioning

confidence: 96%

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Ohashi¹,

Wang

Yang

et al. 2019

Hepatology

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) enhances the growth and recurrence of colorectal cancer (CRC) liver metastasis. With the rising prevalence of NAFLD, a better understanding of the molecular mechanism underlying NAFLD‐associated liver metastasis is crucial. Tumor‐associated macrophages (TAMs) constitute a large portion of the tumor microenvironment that promotes tumor growth. NOD‐like receptor C4 (NLRC4), a component of an inflammasome complex, plays a role in macrophage activation and interleukin (IL)‐1β processing. We aimed to investigate whether NLRC4‐mediated TAM polarization contributes to metastatic liver tumor growth in NAFLD. Wild‐type and NLRC4‐/‐ mice were fed low‐fat or high‐fat diet for 6 weeks followed by splenic injection of mouse CRC MC38 cells. The tumors were analyzed 2 weeks after CRC cell injection. High‐fat diet–induced NAFLD significantly increased the number and size of CRC liver metastasis. TAMs and CD206‐expressing M2 macrophages accumulated markedly in tumors in the presence of NAFLD. NAFLD up‐regulated the expression of IL‐1β, NLRC4, and M2 markers in tumors. In NAFLD, but not normal livers, deletion of NLRC4 decreased liver tumor growth accompanied by decreased M2 TAMs and IL‐1β expression in tumors. Wild‐type mice showed increased vascularity and vascular endothelial growth factor (VEGF) expression in tumors with NAFLD, but these were reduced in NLRC4‐/‐ mice. When IL‐1 signaling was blocked by recombinant IL‐1 receptor antagonist, liver tumor formation and M2‐type macrophages were reduced, suggesting that IL‐1 signaling contributes to M2 polarization and tumor growth in NAFLD. Finally, we found that TAMs, but not liver macrophages, produced more IL‐1β and VEGF following palmitate challenge. Conclusion: In NAFLD, NLRC4 contributes to M2 polarization, IL‐1β, and VEGF production in TAMs, which promote metastatic liver tumor growth.

show abstract

Section: Discussionmentioning

confidence: 96%

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Ohashi¹,

Wang

Yang

et al. 2019

Hepatology

View full text Add to dashboard Cite

show abstract

“…A recent report showed that liver metastasis risk was underestimated and it was even higher in patients with CRC with cirrhosis of the liver [ 14 ]. In the report, however, neither diagnostic modalities for liver metastasis nor occurrence of HCC were specified.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma incidentally detected at second hepatectomy for repeated colorectal liver metastasis in a patient with hepatitis C virus-related cirrhosis: a case report

et al. 2016

View full text Add to dashboard Cite

BackgroundIt has been reported that liver metastasis rarely occurs in a cirrhotic/hepatitic liver. Thus, coexistence of liver metastasis and hepatocellular carcinoma has been scarcely reported. To the best of our knowledge, there are no cases with hepatocellular carcinoma, which developed during an observational period after hepatectomy for colorectal liver metastasis, in the worldwide English literature. Here we present a case of hepatocellular carcinoma which occurred during a period between the first and second hepatectomy for repeated colorectal liver metastasis.Case presentationA 65-year-old Japanese woman underwent rectal resection for advanced rectal cancer. Hepatitis C cirrhosis was diagnosed at that time and antiviral therapy was offered but rejected because of socioeconomic reasons. At the age of 68, she developed two colorectal liver metastases originating from the rectal cancer, which were treated by local ablation and partial hepatectomy. At the age of 71, solitary recurrent colorectal liver metastasis was observed adjacent to the previously ablated lesion in segment 4, and thus segmentectomy 4 was performed. During surgery, a small tumor in segment 8 was incidentally identified. Taking into account her history, the tumor was considered to be recurrent colorectal liver metastasis and it was extirpated by partial hepatectomy. However, the segment 4 tumor was diagnosed as recurrent colorectal liver metastasis on the basis of histological findings and the segment 8 tumor was diagnosed as hepatocellular carcinoma. Although she had a cut surface abscess postoperatively, she was discharged from hospital 21 days after the surgery and is currently doing well 18 months after the second hepatectomy. She is currently receiving interferon and ribavirin therapy to eliminate hepatitis C virus.ConclusionsIf antiviral therapy was performed earlier for the present case and viral elimination was achieved, hepatocellular carcinoma might not have developed. This case reemphasizes the importance of antiviral therapy for preventing carcinogenesis of hepatocellular carcinoma in patients with viral hepatitis even if they have other cancers.

show abstract

“…Aging may also contribute to changes in liver tissue stiffness, as well as increase the likelihood of tissue fibrosis following an acute injury or illness [8][9][10]. The literature on the effect of such biomechanical alterations on tumor growth in the liver is seemingly inconsistent: some report low incidence of CRC metastases in cirrhotic livers (with accompanying fibrosis) [11], while others have reported that the risk of CRC liver metastases may be higher in patients with cirrhosis [12]. Still others report that stiff tissues can promote tumor growth and metastasis in the liver (e.g., [13]).…”

Section: Introductionmentioning

confidence: 99%

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

Brodin

Nishii

Frieboes

et al. 2020

Preprint

View full text Add to dashboard Cite

Colorectal carcinoma (CRC) and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect primary and metastatic tumor growth in liver tissues, the role of these properties in driving or inhibiting metastatic inception remains poorly understood. This study uses a multi-model approach to study the effect of tumor-parenchyma biomechanical interactions on metastatic seeding and growth; the framework also allows investigating the impact of changing tissue biomechanics on tumor dormancy and "reawakening." We employ a detailed poroviscoelastic (PVE) model to study how tumor metastases deform the surrounding tissue, induce pressure increases, and alter interstitial fluid flow in and near the metastases. Results from these short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for use in an agent-based model of metastatic seeding and growth in centimeter-scale tissue over months-long time scales. We find that biomechanical tumor-parenchyma interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) may play a key role in tumor cell seeding and growth within liver tissue. These interactions may arrest the growth of micrometastases in a dormant state and can prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors can "reawaken" after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach can yield insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, with the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer. 4/25

show abstract

Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study

Cited by 21 publications

References 26 publications

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

NOD‐like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD

Hepatocellular carcinoma incidentally detected at second hepatectomy for repeated colorectal liver metastasis in a patient with hepatitis C virus-related cirrhosis: a case report

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

Contact Info

Product

Resources

About