| 1. |
- Latacz, Emily, et al.
(författare)
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Histopathological growth patterns of liver metastasis : updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:6, s. 988-1013
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Forskningsöversikt (refereegranskat)abstract
- The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
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| 2. |
- Frentzas, Sophia, et al.
(författare)
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Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases
- 2016
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 22:11, s. 1294-1302
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.
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| 3. |
- van Dam, Pieter-Jan, et al.
(författare)
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International consensus guidelines for scoring the histopathological growth patterns of liver metastasis
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 117:10, s. 1427-1441
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Tidskriftsartikel (refereegranskat)abstract
- Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.
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| 4. |
- Heil, Jan, et al.
(författare)
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Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection-A DRAGON collaborative analysis of 306 patients
- 2022
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 24:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR >2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.
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