Clinical & experimental metastasis
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Clin. Exp. Metastasis · Apr 2018
ReviewImplicating anaesthesia and the perioperative period in cancer recurrence and metastasis.
Cancer, currently the leading cause of death in the population aged less than 85 years, poses a significant global disease burden and is anticipated to continue to increase in incidence in both developed and developing nations. A substantial proportion of cancers are amenable to surgery, with more than 60% of patients undergoing tumour resection. Up to 80% of patients will receive anaesthesia for diagnostic, therapeutic or palliative intervention. ⋯ Disturbingly, drugs used for general anaesthesia (e.g. inhalational vs. intravenous anaesthesia and potentially opioid analgesia) may also affect behaviour of tumour cells and immune cells, suggesting that choice of anaesthetic agent may also be linked to adverse long-term cancer outcomes. Critically, current clinical practice guidelines on the use of anaesthetic techniques, anaesthetic agents and perioperative adjuvants (e.g. anti-inflammatory drugs) during cancer surgery do not take into account their potential effect on cancer outcomes due to a lack of robust prospective data. To help address this gap, we provide an up-to-date review of current clinical evidence supporting or refuting the role of perioperative stress, anaesthetic techniques and anaesthetic agents in cancer progression and review pre-clinical studies that provide insights into biological mechanisms.
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Clin. Exp. Metastasis · Dec 2017
How do organ-specific metastases affect prognosis and surgical treatment for patients with metastatic upper tract urothelial carcinoma: first evidence from population based data.
To evaluate the prognostic roles of organ-specific metastases and analyze the impact of organ-specific metastases on surgical resection of the primary tumor for metastatic upper tract urothelial carcinoma (UTUC) patients. A population-based study using Surveillance, Epidemiology, and End Results database was carried out. Kaplan-Meier analysis were used for survival comparisons. ⋯ However, the presence of liver or lung metastasis could make such surgery become meaningless from the point of survival benefits. Our study showed that brain metastasis independently predicted both unfavorable OS and CSS for metastatic UTUC patients while liver metastasis was only associated with worse OS. More importantly, surgical resection of the primary tumor might still lead to survival benefits for highly selected patients.
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Clin. Exp. Metastasis · Dec 2017
De novo metastasis in breast cancer: occurrence and overall survival stratified by molecular subtype.
Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with first primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. ⋯ The median survival difference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR-/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2-. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment differences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment.
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Clin. Exp. Metastasis · Jan 2017
Use of non-invasive imaging to monitor response to aflibercept treatment in murine models of colorectal cancer liver metastases.
The liver is the most frequent metastatic site in colorectal cancer (CRC), and relevant orthotopic in vivo models are needed to study the efficacy of anticancer drugs in the metastatic setting. A challenge when utilizing such models is monitoring tumor growth during the experiments. In this study, experimental liver metastases were established in nude mice by splenic injection of the CRC cell lines HT29 and HCT116, and the mice were treated with the antiangiogenic drug aflibercept. ⋯ Apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DW-MRI) were highly predictive of treatment response, with increased ADC corresponding well with areas of necrosis observed by histological evaluation of aflibercept-treated xenografts. The results showed that the efficacy of the antiangiogenic drug aflibercept varied between the two models, possibly reflecting unique growth patterns in the liver that may be representative of human disease. Non-invasive imaging, especially MRI and DW-MRI, can be used to effectively monitor tumor growth and treatment response in orthotopic liver metastasis models.
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Clin. Exp. Metastasis · Aug 2016
Endoscopy-guided orthotopic implantation of colorectal cancer cells results in metastatic colorectal cancer in mice.
Advanced stage colorectal cancer (CRC) is still associated with limited prognosis. For preclinical evaluation of novel therapeutic approaches, murine models with orthotopic tumor growth and distant metastases are required. However, these models usually require surgical procedures possibly influencing tumor immunogenicity and development. ⋯ FRI and gelatin zymography did not detect a significantly increased matrix metalloproteinases (MMPs) expression in s.c. implanted tumors while MMP-tracer uptake was significantly enhanced in orthotopic implanted tumors. Neither s.c. nor orthotopic Caco-2 cell implantation resulted in tumor development. We successfully established an endoscopy-based model of metastatic CRC in immunodeficient mice.