The Influence of Liver Resection on Intrahepatic Tumor Growth

Brandt, Hannes Hermann; Nißler, Valérie; Croner, Roland S.

doi:10.3791/53946

Cited by 5 publications

(6 citation statements)

References 26 publications

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“…50% PH-induced acute liver injury. The mice were anesthetized by isoflurane inhalation (anesthetic induction on 5% isoflurane at a flow of 10 l/min, followed by anesthetic maintenance using an inspiratory fraction of 1.8-2.2% at a flow of 1 l/min) (19). The caudate lobe, left lateral lobe and left median lobe were then resected to generate the LR model (50% PH) (18,19).…”

Section: Methodsmentioning

confidence: 99%

Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy

Shao

Jiang

et al. 2021

Exp Ther Med

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Dysbiosis of the gut microbiota has important roles in various diseases and pathological states of the host. However, the changes of the gut microbiota during partial hepatectomy (PH)-induced acute liver injury have so far remained elusive. The present study investigated the gut microbiome and its related pathways following PH-induced acute liver injury. A total of 50 male C57/BL6 mice were divided into a normal control (NC), sham-operation and liver resection (LR) group (50% PH). Samples were collected at 3 and 14 days post-operation to obtain specimens for the Sham3, Sham14, LR3 and LR14 groups (10 mice/group). Specimens of NC group (n=10) were obtained at the same time as those of Sham3 group. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic chemical analyzer and the gut microbiota was assessed by 16S ribosomal RNA gene sequencing of small intestinal contents. The serum levels of ALT and AST in the LR3 group were significantly increased, while those in the LR14 group were decreased again to near-normal levels. In the LR3 group, the operational taxonomic units, species richness (Chao1) and species diversity (Shannon and Simpson indices) were decreased, although without any significant difference. Furthermore, in the LR3 group, significant Cyanobacteria enrichment and Fusobacteria depletion compared with the NC and Sham3 groups was observed, while in the LR14 group, a significant depletion of the abundance of Verrucomicrobia, Chloroflexi and Deferribacteres compared to the LR3 group was obtained. The abundance of Firmicutes was increased in the LR3 group and decreased again in the LR14 group. However, the abundance of Bacteroidetes and Actinobacteria decreased in the LR3 group and increased again in the LR14 group. The alterations of the gut microbiota at the genus level were also revealed, as significant increases in Chloroplast, Curvibacter, Pelomonas, Ruminococcaceae UCG-005 and Blautia and a sharp decrease in Akkermansia and Eubacterium coprostanoligenes were caused by acute liver injury. Furthermore, functional metagenome prediction was performed by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States based on the Greengenes database, revealing alterations in signal transduction, transcription and cell motility, as well as metabolism of amino acids, lipids, glucose, cofactors and terpenoids, and xenobiotics pathways. An improved understanding of the structural and functional changes of the gut microbiota following 50% PH-induced acute liver injury and repair may provide novel strategies for the recovery of hosts undergoing hepatectomy.

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Section: Methodsmentioning

confidence: 99%

Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy

Shao

Jiang

et al. 2021

Exp Ther Med

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“…As pHx has been linked to a potentially prometastatic effect in injection models of colorectal liver metastasis before ( 12 – 14 ), we were curious about the impact of resection in our model of orthograde metastasis. Regarding the metastatic burden in the animals, we found no difference in the total metastatic volume within the liver on POD7 between control, SHAM, and pHx mice.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, these models are rather artificial and exclude the crucial influence of the microenvironment of the primary tumor on CRC metastasis as well as the significant changes that cancer cells undergo before entering the bloodstream (e.g. epithelial-mesenchymal transition (EMT)) ( 12 – 15 ). As the liver is often the tumor manifestation defining the patients’s prognosis, in several cases of synchronous metastasis of CRC, resection of LM is performed prior to the resection of the primary tumor.…”

Section: Introductionmentioning

confidence: 99%

Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver

Luenstedt,

Hoping,

Feuerstein

et al. 2024

Front. Immunol.

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BackgroundResection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.MethodsCRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.ResultsMice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.ConclusionsRegenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.

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“…According to the liver structure of mice, it can be divided into 7 liver lobes in detail, or simply divided into 4 lobes, namely, left lobe, middle lobe, right lobe and caudate lobe. Although 70% of PH models are the most commonly used models for studying LR, 30%, 50%, and 90% of PH are performed according to different experimental designs ( Myronovych et al, 2008 ; Brandt et al, 2016 ; Shao et al, 2021 ). The literature shows that laparoscopic surgery has been carried out on this basis ( Ypsilantis et al, 2020 ).…”

Section: Injury Models For Lrmentioning

confidence: 99%

Unveiling the power of microenvironment in liver regeneration: an in-depth overview

Hu,

Wang,

et al. 2023

Front. Genet.

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The liver serves as a vital regulatory hub for various physiological processes, including sugar, protein, and fat metabolism, coagulation regulation, immune system maintenance, hormone inactivation, urea metabolism, and water-electrolyte acid-base balance control. These functions rely on coordinated communication among different liver cell types, particularly within the liver’s fundamental hepatic lobular structure. In the early stages of liver development, diverse liver cells differentiate from stem cells in a carefully orchestrated manner. Despite its susceptibility to damage, the liver possesses a remarkable regenerative capacity, with the hepatic lobule serving as a secure environment for cell division and proliferation during liver regeneration. This regenerative process depends on a complex microenvironment, involving liver resident cells, circulating cells, secreted cytokines, extracellular matrix, and biological forces. While hepatocytes proliferate under varying injury conditions, their sources may vary. It is well-established that hepatocytes with regenerative potential are distributed throughout the hepatic lobules. However, a comprehensive spatiotemporal model of liver regeneration remains elusive, despite recent advancements in genomics, lineage tracing, and microscopic imaging. This review summarizes the spatial distribution of cell gene expression within the regenerative microenvironment and its impact on liver regeneration patterns. It offers valuable insights into understanding the complex process of liver regeneration.

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The Influence of Liver Resection on Intrahepatic Tumor Growth

Cited by 5 publications

References 26 publications

Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy

Characteristics of mouse intestinal microbiota during acute liver injury and repair following 50% partial hepatectomy

Partial hepatectomy accelerates colorectal metastasis by priming an inflammatory premetastatic niche in the liver

Unveiling the power of microenvironment in liver regeneration: an in-depth overview

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