Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

Weber, Jean-Christophe; Nakano, Hiroshi; Bachellier, Philippe; Oussoultzoglou, Elíe; Inoue, Keiichiro; Shimura, Hiroshi; Wolf, Philippe; Chenard-Neu, Marie-Pierre; Jaeck, Daniel

doi:10.1016/s0002-9610(01)00656-0

Cited by 61 publications

(53 citation statements)

References 28 publications

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“…A recent large meta-analysis examining nearly 10000 patients reported a 5-year survival of only 17.1% for patients with four or more CLMs [28] . Other studies have found no difference in survival based on the number of tumors with 5-year survival ranging from 40%-50% regardless of tumor burden [9,27,[29][30][31][32] . The reason for these differences may be related to patient selection, differences in surgical approach (resection only, resection plus ablation, etc.…”

Section: Number Of Liver Metastasesmentioning

confidence: 87%

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Surgery for colorectal liver metastases: The evolution of determining prognosis

Spolverato

Ejaz

Azad

et al. 2013

WJGO

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Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative factors, these have been inconsistent in accurately determining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcriptase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predicting survival after surgical resection have been supported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver metastasis. We herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergoing resection with curative intent.© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Colorectal; Metastasis; Prognosis; Risk score; Molecular markers; Outcomes Core tip: Historically, prognosis after resection has been largely assessed based on preoperative clinicopathologic features. Data validating the prognostic value of patient and tumor specific factors have been mixed, with many recent studies showing these scoring systems to correlate poorly with survival. Rather, there has been an emerging interest in biological or molecular markers of prognosis to more effectively assess patient prognosis after resection of colorectal liver metastasis. In this review, we discuss past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergoing resection with curative intent.

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Section: Number Of Liver Metastasesmentioning

confidence: 87%

“…Several studies have reported that a higher number of CRLM lesions is a poor prognostic factor [28][29][30][31][32] . A recent large meta-analysis examining nearly 10000 patients reported a 5-year survival of only 17.1% for patients with four or more CLMs [28] .…”

Section: Number Of Liver Metastasesmentioning

confidence: 99%

Surgery for colorectal liver metastases: The evolution of determining prognosis

Spolverato

Ejaz

Azad

et al. 2013

WJGO

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“…The Ki67 labelling index was significantly higher in the PVE group than controls. A high Ki67 labelling index is an adverse prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (Weber et al, 2001). Identification of the Ki67 labelling index before and after PVE in the same patient would have been of interest, but pre-PVE biopsy was not carried out for ethical reasons as it carries a risk of tumour seeding.…”

Section: Discussionmentioning

confidence: 99%

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

et al. 2009

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Portal vein embolisation (PVE) is used to increase the remnant liver volume before major liver resection for colorectal metastases. The resection rate after PVE is 60 -70%, mainly limited by disease progression. The effect of PVE on tumour growth rate has not been investigated. The objective of this study was to compare the growth characteristics of resected colorectal liver metastases in patients undergoing pre-operative PVE with those of matched controls who had not undergone PVE. There were 22 patients who had undergone preoperative PVE and 20 matched controls. Tumour growth rate was calculated by the change in tumour volume (CT/MRI volumetric assessment) from diagnosis to resection. Resected histological specimens were examined by two histopathologists independently for cell differentiation, percentage tumour cell necrosis and mitotic rate. Immunochemical staining with Ki67 was carried out using the MIB-1 monoclonal antibody and quantified using a Glasgow cell-counting graticule. The groups were comparable in demographics, stage of primary disease, volume of liver metastases at presentation and chemotherapy received. The tumour growth rate calculated from imaging was more rapid in the PVE group compared with that in controls (control: 0.05 ± 0.25 ml day À1 , PVE: 0.36 ± 0.68 ml day À1 , P ¼ 0.06). Histology showed no difference in the degree of differentiation, extent of necrosis or apoptosis between the two groups. However, mitotic rate was higher post PVE, as was the proliferation index Ki67 (P ¼ 0.04). This study has confirmed that tumour growth rate increased following PVE and that this is related to increased tumour cell division.

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“…It is well described that desmoplastic encapsulation of colorectal liver metastases corresponds with good survival, a minimal risk of local recurrence, and small tumor size. 3,[7][8][9][10][11][12][13] It has even been reported that the thicker the desmoplastic rim is, the better the prognosis. 11,12 These data corroborate that the desmoplastic pattern might teleologically represent a hepatic defense mechanism, at least as the general rule.…”

Section: Figurementioning

confidence: 99%

“…Several studies comparing metastases with and without desmoplastic encapsulation have reported a positive impact on survival of desmoplasia per se. [7][8][9][10][11][12][13] In consequence, the aim of the present study was in a population treated according to modern guidelines and indications to examine the prognostic value of the histological growth patterns for survival.…”

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confidence: 99%

The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

et al. 2014

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Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217 consecutive patients, liver resected between 2007 and 2011 due to hepatic metastases from colorectal adenocarcinoma. The growth patterns were assessed on archival hematoxylin and eosin-stained tissue sections. In 150 metastases, the density of the immune cell infiltrate at the tumor periphery was judged by a semi-quantitative method. The prevalence of the pushing-type, the desmoplastic-type, and the replacement-type was 33%, 32%, and 11%, respectively; 24% of the metastases displayed a mixed pattern. Kaplan-Meier analysis and Cox regression demonstrated a prognostic significance of the growth patterns (P ¼ 0.0006, log-rank test), as the replacement pattern appeared as an independent predictor of poor overall survival. For patients with replacement growth, the hazard of death was 2-2.5 times higher than for patients with pushing growth (P ¼ 0.004, cox regression) or mixed growth (P ¼ 0.01), and nearly four times higher than for patients with desmoplastic growth (Po0.0001). The negative prognostic effect of the replacement growth pattern was even more pronounced after adjusting for tumor size. Desmoplastic growth corresponded with small tumor size, dense lymphocytic infiltration and a more favorable prognosis. Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases. Modern Pathology (2014) 27, 1641-1648; doi:10.1038/modpathol.2014.4; published online 23 May 2014Keywords: colorectal cancer; growth pattern; histopathology; liver; metastasis; prognosis; survival During the last 5-10 years, major advances have been made in both the medical and surgical treatment of liver metastases from colorectal carcinoma. The number of patients who undergo liver resection with curative intent has therefore increased significantly. However, so far, little is known on the biological, clinical, and histopathological features that determine prognosis after hepatic resection. The revised and more active treatment strategy has thus fostered a demand for new and better prognostic and predictive markers that can be used for selecting the right treatment regimen for each patient. For primary colorectal cancer, the malignant transformation from adenoma to carcinoma is by now very well described; far less described are the events that govern the progression of metastases in the liver. A greater understanding of the diverse infiltration mechanisms of the metastases, including the intricate interaction with the hepatic microenvironment, might lead to new prognostic and therapeutic prospects.Vermeulen et al 1 identified three histological growth patterns for colorectal liver metastases, suggesting biological differences: (i) a pushing growth pattern, in which the metastasis e...

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Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

Cited by 61 publications

References 28 publications

Surgery for colorectal liver metastases: The evolution of determining prognosis

Surgery for colorectal liver metastases: The evolution of determining prognosis

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

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