Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis – Systematic review and meta-analysis

Pavel, Mihai-Calin; Casanova, Raquel; Estalella, Laia; Memba, Robert; Llàcer-Millán, Erik; Julià, Elisabet; Merino, Sandra; Geoghegan, Justin; Jorba, Rosa

doi:10.1016/j.ejso.2022.12.017

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…However, some conflicting evidence exists regarding chemotherapy's impact on liver regeneration. A recent meta-analysis suggests that neoadjuvant chemotherapy has no negative impact on post-hepatectomy liver regeneration [9,22]. Such findings contradict our current study, which revealed a significant decrease in regenerated liver volume among patients with CRLM who underwent chemotherapy when compared to controls who underwent surgery for benign pathology.…”

Section: Discussioncontrasting

confidence: 99%

“…A substantial number of CRLM patients, previously categorized as unresectable, can now undergo complete resection due to the implementation of innovative strategies that facilitate the manipulation of liver volume (4). However, chemotherapy's impact on liver regeneration remains controversial, with conflicting evidence existing [2,8,9]. A healthy liver rapidly restores its mass, particularly within the initial week following a major resection.…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients

Račkauskas,

Lukšaitė-Lukštė,

Stulpinas

et al. 2024

JPM

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An ongoing debate surrounds the impact of chemotherapy on post-hepatectomy liver regeneration in patients with colorectal cancer liver metastases (CRLM), with unclear regulatory mechanisms. This study sought to delve into liver regeneration post-resection in CRLM patients, specifically examining the roles of hepatocyte growth factor (HGF) and transforming growth factor β1 (TGF-β1). In this longitudinal observational study, 17 patients undergoing major liver resection for CRLM and 17 with benign indications as controls were enrolled. Liver regeneration within 30 postoperative days was assessed via CT, considering clinicopathological characteristics, liver enzymes, liver stiffness by elastography, and the impact of HGF and TGF-β1 on liver regeneration. The results revealed that the control group exhibited significantly higher mean liver regeneration volume (200 ± 180 mL) within 30 days postoperatively compared to the CRLM group (72 ± 154 mL); p = 0.03. Baseline alkaline phosphatase (AP) and TGF-β1 blood levels were notably higher in the CRLM group. Immunohistochemical analysis indicated a higher proportion of CRLM patients with high TGF-β1 expression in liver tissues compared to the control group (p = 0.034). Correlation analysis showed that resected liver volume, baseline plasma HGF, AP, and albumin levels significantly correlated with liver regeneration volume. However, in multivariable analysis, only resected liver volume (β: 0.31; 95% CI: 0.14–0.47, p = 0.01) remained significant. In conclusion, this study highlights compromised liver regeneration in CRLM patients post-chemotherapy. Additionally, these patients exhibited lower serum TGF-β1 levels and reduced TGF-β1 expression in liver tissue, suggesting TGF-β1 involvement in mechanisms hindering liver regeneration capacity following major resection after chemotherapy.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients

Račkauskas,

Lukšaitė-Lukštė,

Stulpinas

et al. 2024

JPM

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Using machine learning approach for screening metastatic biomarkers in colorectal cancer and predictive modeling with experimental validation

Ahmadieh-Yazdi,

Mahdavinezhad,

Tapak

et al. 2023

Sci Rep

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Colorectal cancer (CRC) liver metastasis accounts for the majority of fatalities associated with CRC. Early detection of metastasis is crucial for improving patient outcomes but can be delayed due to a lack of symptoms. In this research, we aimed to investigate CRC metastasis-related biomarkers by employing a machine learning (ML) approach and experimental validation. The gene expression profile of CRC patients with liver metastasis was obtained using the GSE41568 dataset, and the differentially expressed genes between primary and metastatic samples were screened. Subsequently, we carried out feature selection to identify the most relevant DEGs using LASSO and Penalized-SVM methods. DEGs commonly selected by these methods were selected for further analysis. Finally, the experimental validation was done through qRT-PCR. 11 genes were commonly selected by LASSO and P-SVM algorithms, among which seven had prognostic value in colorectal cancer. It was found that the expression of the MMP3 gene decreases in stage IV of colorectal cancer compared to other stages (P value < 0.01). Also, the expression level of the WNT11 gene was observed to increase significantly in this stage (P value < 0.001). It was also found that the expression of WNT5a, TNFSF11, and MMP3 is significantly lower, and the expression level of WNT11 is significantly higher in liver metastasis samples compared to primary tumors. In summary, this study has identified a set of potential biomarkers for CRC metastasis using ML algorithms. The findings of this research may provide new insights into identifying biomarkers for CRC metastasis and may potentially lay the groundwork for innovative therapeutic strategies for treatment of this disease.

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TGF β1 negatively impacts liver regeneration under chemotherapy

Račkauskas,

Lukšaitė-Lukštė,

Stulpinas

et al. 2023

Preprint

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Background: In the modern surgical and chemotherapy era metastatic liver disease is in the renaissance, enabling to extend patient's life with metastatic liver disease. However, the primary limiting factor to more radical surgical treatment is liver volume, particularly in patients with chemotherapy-induced liver damage. Since results regarding whether chemotherapy has an impact on liver volume regeneration are ambiguous, we have aimed to analyze liver regeneration and the factors influencing it. Methods: A prospective cohort study was performed. Patient inclusion criteria were as follows: patients between 18 and 90 years; liver resection of at least 2 segments either for benign or colorectal cancer metastasis; patients who underwent liver resection due to metastatic disease had to have previous chemotherapy treatment. All patients were divided into 2 groups – control and chemotherapy groups. Analysis of demographics, perioperative data, liver enzymes, liver stiffness, and liver volume was carried out, as well as the impact on regeneration marker expression in serum and liver tissue. Results: 34 patients in all were involved in this trial, and they were split into two groups: chemotherapy and control. The two groups were similar. Except for comorbidities, there were no variations between the perioperative and demographic data. In the chemotherapy group, regenerated liver volume was lower compared to control, 1240.5±69.6 vs 1525.3±106.6 ml p-0.039. Further analysis revealed that the chemotherapy group had increased anti-regenerative TGF β1 expression compared to control in serum and liver tissue, p-0.02 and p-0.034. Conclusions: The present study showed that chemotherapy is associated with lower regenerated volume in patients who received resection. Anti-regenerative TGFβ1 marker expression in liver tissue and serum might have an impact on regenerated liver volume, however, the exact mechanisms involved in decreased regeneration are further to be studied.

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Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis – Systematic review and meta-analysis

Cited by 3 publications

References 51 publications

The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients

The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients

Using machine learning approach for screening metastatic biomarkers in colorectal cancer and predictive modeling with experimental validation

TGF β1 negatively impacts liver regeneration under chemotherapy

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