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© Ordem dos Médicos 2015, Introduction: Surgery is the only potentially curative treatment for patients with colorectal liver metastases, resulting in 5-year survival rates of 36 - 58. Although many studies have been performed to determine prognostic factors for tumor recurrence and survival after resection of colorectal liver metastases, there are few prognostic scoring systems stratifying patients undergoing surgery for colorectal liver metastases into risk group models. Objectives: To identify, evaluate and compare the existing prognostic scores for survival after surgery for resection of colorectal liver metastases. Material and methods: Electronic search in PubMed, Cochrane and Embase from 1990 to 2013 using the terms ' hepatic resection', ' colorectal cancer' , 'liver metastasis', ' hepatectomy', ' prognostic' , and ' score' . Only studies proposing a prognostic model or risk stratification based on clinical and/or pathological variables were included. Results: From 1996 to June 2013, 19 scoring systems were identified, including one nomogram. Thirty prognostic factors were identified although none of the factors was common to all prognostic models. The 4 factors most often included were: number of liver metastases, regional lymph node metastization of primary tumor, preoperative CEA level and maximum size of metastases. The median study sample size was 305 patients (81-1 568 patients) and median follow-up was 33 months (16-54 months). All studies were retrospective and used the Cox proportional hazards model for multi-variable analysis. Conclusion: Several factors have been constantly reported as having prognostic value after liver resection of colorectal livermetastases, although there is no consensus on the ideal scoring system.

Copyright: © 2013 Casimiro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome., The work was supported in part by grants from the National Institutes of Health (National Cancer Institute) CA69158 and CA143057 (to TAG and KM); and FCT Fellowships SFRH/BPD/34801/2007, SFRH/BD/45219/2008 and SFRH/BD/44716/2008 (to SC, JT-C and IA).

© 2015 Elsevier Inc. All rights reserved., Introduction: DNA damaging agents and ionizing radiation used in the therapy of human cancers can induce senescence of cancer cells. Senescent cells exhibit a secretory phenotype (senescence-associated secretome [SAS]) that can affect cancer cell behavior and, eventually, clinical prognosis. We assessed the effects of the SAS on the induction of epithelial-to-mesenchymal transition (EMT) in vitro and in clinical samples from patients with rectal cancer who had undergone neoadjuvant chemoradiotherapy (CRT). Materials and methods: Colorectal cancer cells (HCT 116) were induced into senescence by exposure to either 5-fluorouracil (5-FU) or doxorubicin. The senescent state was confirmed by staining for senescence-associated β-galactosidase (SA-β-Gal). The paracrine effects of SASs were assessed on proliferating HCT 116 cells. The quantified parameters were cell proliferation, invasive capacity, and induction of EMT. Senescence and EMT in clinical samples were assessed by the expression levels (reverse transcriptase-quantitative polymerase chain reaction) of genes related to senescence and EMT after laser-assisted microdissection of cancer cell clusters that stained either positive or negative for SA-β-Gal. Results: We have shown that cultured colon cancer cells induced into senescence by exposure to 5-FU exhibit a SAS capable of paracrine induction of EMT in colon and rectal cancer cell lines and increased cell invasion in vitro. Using laser-assisted microdissection, we found that in rectal cancer samples from patients treated with neoadjuvant CRT, tumor cell niches enriched for senescent cells bookmark regions of increased mRNA expression levels of EMT-related proteins (Slug, Snail, vimentin) compared with the nearby senescent-null tumor cell niches. Conclusion: We have provided, first-hand, strongly suggestive evidence that senescent cancer cells emerging in the context of neoadjuvant CRT for rectal cancer influenced the tumor microenvironment by promoting EMT by way of short-range interactions., This work was supported by the Histology and Comparative Pathology Laboratory and the Bioimaging Unit of the Instituto de Medicina Molecular for technical support. J. Tato-Costa, S. Casimiro, I. Alho, and P. Pereira were supported by fellowships from Fundação para a Ciência e Tecnologia (grants SFRH/BD/45219/2008, SFRH/BPD/34801/2007, SFRH/BD/44716/2008, and SFRH/BD/45502/2008, respectively). João Ferreira receives support from Gulbenkiam Foundation (grant 96526/2009).

© Springer Science+Business Media Dordrecht 2014, Colorectal cancer (CRC) is the third most common malignant disease in men and the second in women worldwide. CRC relapse occurs mostly in liver and lungs, decreasing the 5-year survival to 6 %. Metadherin (MTDH) is overexpressed in several types of cancer, has been implicated in proliferation, invasion, metastasis, angiogenesis, and chemoresistance, and is a factor of poor prognosis in CRC. In this work we addressed the prognostic significance of MTDH expression in CRC progression to the lungs. We found that MTDH gene was more frequently amplified (copy number >1.8) in patients with CRC and relapse to the lung, when compared to patients without lung metastases (17.4 vs 100 %; p < 0.001). We observed a correlation between MTDH gene copy number and MTDH expression by IHC (p = 0.0001). Next we also analyzed MTDH expression by IHC in samples from 85 patients diagnosed with CRC, stage II or III, M0, with at least 3 years of follow-up. Kaplan-Meier survival analysis showed that lung relapse-free survival (HR 5.29, 95 % CI 1.90-14.77, p = 0.0004), liver relapse-free survival (HR 8.59, 95 % CI 0.99-74.18, p = 0.003), relapse-free survival (HR 4.85, 95 % CI 1.88-12.45, p = 0.0003) and overall survival (HR 3.75, 95 % CI 1.15-12.18, p = 0.018) were significantly lower in the group with high MTDH expression. Multivariate analysis showed that high MTDH expression was an independent factor for all outcomes. This study demonstrates that high MTDH expression is a biomarker of relapse in CRC, including lung-specific relapse. Determination of MTDH expression in primary CRC may be useful in the earlier detection of lung metastases in patients with high expression and increased risk., This project was supported by a Grant from Fundação para a Ciência e Tecnologia (PIC/IC/82821/2007).S. Casimiro was supported by a Post-Doctoral Grant (SFRH/BPD/34801/2007) and J. Tato-Costa by a PhD Grant (SFRH/BD/45219/2008) from Fundação para a Ciência e Tecnologia.