Growth pattern of colorectal liver metastasis as a marker of recurrence risk

Eefsen, Rikke Løvendahl; Vermeulen, Peter; Christensen, Ib Jarle; Lærum, Ole Didrik; Mogensen, Marie Benzon; Rolff, Hans Christian; Eynden, Gert G. Van den; Høyer‐Hansen, Gunilla; Østerlind, Kell; Vainer, Ben; Illemann, Martin

doi:10.1007/s10585-015-9715-4

Cited by 68 publications

(55 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Factors such as tumour growth pattern and collagen architecture, both closely associated with solid stress, have been shown to have prognostic values. Growth pattern, histologically categorized as pushing vs. replacing phenotypes, has been linked to overall survival [36] and recurrence risk [37]. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Solid stress and elastic energy as measures of tumour mechanopathology

et al. 2016

View full text Add to dashboard Cite

Solid stress and tissue stiffness affect tumour growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumours, the measurement of solid stresses is challenging. Here, we show that two-dimensional spatial mappings of solid stress and the resulting elastic energy in excised or in situ tumours with arbitrary shapes and wide size ranges can be obtained via three distinct and quantitative techniques that rely on the measurement of tissue displacement after disruption of the confining structures. Application of these methods in models of primary tumours and metastasis revealed that: (i) solid stress depends on both cancer cells and their microenvironment; (ii) solid stress increases with tumour size; and (iii) mechanical confinement by the surrounding tissue significantly contributes to intratumoural solid stress. Further study of the genesis and consequences of solid stress, facilitated by the engineering principles presented here, may lead to significant discoveries and new therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Solid stress and elastic energy as measures of tumour mechanopathology

et al. 2016

View full text Add to dashboard Cite

show abstract

“…uPAR is up-regulated at the invasive front of the tumour in primary CRC and a high uPAR expression has been correlated to an inferior outcome [25]. Therefore it is interesting that most uPAR is found in liver metastases with desmoplastic GP as this type of metastases has been shown to be associated to a longer recurrence free survival independent of neo-adjuvant therapy [33]. It is very likely that uPAR in desmoplastic liver metastases is involved in a tissue remodelling process.…”

Section: Discussionmentioning

confidence: 99%

“…Sections of 3 μm were cut from the formalin fixed paraffin embedded tissue blocks. The sections were stained with Haematoxylin & Eosin (H&E) and Gordon-Sweet reticulin [26,33]. A total of 45 tissue slides lacked a representative tumour-liver interface and were excluded from further analysis.…”

Section: Histologymentioning

confidence: 99%

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

Eefsen

Engelholm

Alpízar‐Alpízar

et al. 2015

Cancer Microenvironment

Self Cite

View full text Add to dashboard Cite

Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p=0.01) or replacement GP (p=0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p=0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p=0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p= 0.01) or pushing GP (p=0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated.

show abstract

“…Adam et al 30 Umeda et al 31 Huang et al 32 Mavros et al 33 Viganò et al 34 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Norén et al 38 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Dupré et al 41 Liang et al 43 Rhu et al 44 Sultana et al 45 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 Engstrand et al 50 Goffredo et al 51 lmai et al 52 Koch et al 53 Laengle et al 54 Ledys et al 55 Liao et al 56 Lionti et al 57 Loosen et al 58 Makowiec et al 59 Margonis et al 60 Marques et al 24 Oshi et al 61 Palkovics et al 62 Shigematsu et al 63 Vallance et al 64 Wang et al 23 Wang et al 65 Zheng et al 66 Prediction interval 0·1 0 ·5 1 2 10…”

Section: Fig 2 Forest Plots Showing Impact Of Primary Tumour Locatiomentioning

confidence: 99%

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Wang

Zhang

Wang

et al. 2019

British Journal of Surgery

View full text Add to dashboard Cite

Background Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta‐analysis was undertaken to evaluate its prognostic value. Methods References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease‐free survival after hepatic resection between patients with CRLM originating from right‐ or left‐sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random‐effects model. Meta‐regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. Results The final analysis included 21 953 patients from 45 study cohorts. Compared with left‐sided primary tumour location, right‐sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease‐free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right‐sided primary tumour location on overall survival was more prominent in the non‐Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). Conclusion This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.

show abstract

Growth pattern of colorectal liver metastasis as a marker of recurrence risk

Cited by 68 publications

References 50 publications

Solid stress and elastic energy as measures of tumour mechanopathology

Solid stress and elastic energy as measures of tumour mechanopathology

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Contact Info

Product

Resources

About