891 research outputs found

    Extramural Venous Invasion as Prognostic Factor of Recurrence in Stage 1 and 2 Colon Cancer

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    Aim. Extramural venous invasion (EMVI) is a prognostic indicator in patients with colorectal cancer. However, its additional value in patients with stage 1 and 2 colorectal cancer is uncertain. In the present study, the incidence of EMVI and the hazard ratio for recurrence in patients with stage 1 and 2 colon cancer were studied. Methods. 184 patients treated for stage 1 and 2 colon cancer were included with a follow-up of at least 5 years. Chart review was performed and EMVI was assessed by two separate pathologists. EMVI was scored with additional caldesmon staining on the resection specimen. Primary outcomes were recurrence-free survival (RFS) measured through the Cox regression analysis and prevalence of EMVI. Results. There were 10 cases of EMVI and 3 cases of intramural venous invasion (IMVI) all occurring in patients with stage 2 disease corresponding to a prevalence of 9%. Thirty-one percent of the patients with venous invasion experienced recurrence versus 14% in patients without, corresponding with a hazard ratio of 2.39 (p=0.11). Conclusion. The present study demonstrates a trend towards an increased risk of recurrence in patients with stage 2 colon cancer with venous invasion. This warrants consideration of adjuvant chemotherapy despite the lack of lymph node metastases

    Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

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    BACKGROUND: Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear. METHODS: From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression. RESULTS: EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p  pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone

    The Relationship Between MR Demonstration of Extramural Venous Invasion and Nodal Disease in Rectal Cancer

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    Β© 2008 Libertas Academica Ltd. All rights reserved.Results: Compared with histology, an MR score of >2 was found to have 100% sensitivity (95% CI: 77%–100%) and 89% specificity (95% CI: 79%–96%) in identifying EMVI involving veins >3 mm in diameter. An EMVI score of >2 was had a sensitivity of 56% (95% CI: 30%–80%) and specificity of 81% (95% CI: 69%–90%) for identifying patients with stage N2 disease.Conclusions: EMVI score of >2 on T2-weighted MR imaging has a high sensitivity and specificity for histopathologically proven extramural venous invasion involving venules β‰₯3 mm in diameter. However, EMVI scores have only moderate sensitivity in the predicting nodal involvement.Purpose: To investigate the relationship between extramural venous invasion (EMVI) detected at T2-weighted MRI and nodal disease rectal cancer compared with histopathology.Materials and Methods: The MR imaging of 79 consecutive patients with rectal cancer who underwent primary rectal surgery without neoadjuvant treatment were reviewed. MR images were scored by an expert radiologist for the presence and degree of EMVI using a five point scale blinded to pathological findings. Receiver operating characteristic curve analyses were performed to determine the sensitivity and specificity of MRI scoring in predicting EMVI and nodal disease at histopathology

    A Mechanistic Investigation of the Relationship Between Extramural Vascular Invasion (EMVI) and CpG Island Methylator Phenotype (CIMP) in Rectal Cancer

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    Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer death worldwide. Each year, one million people will develop CRC, and 40-50% will die within five years. Furthermore, rectal and distal sigmoid cancers are known to present at a later stage and have a poorer prognosis than other colonic cancers. Rectal cancers that demonstrate pathological extramural vascular invasion (EMVI-positive) are known to have a poorer prognosis than those that do not (EMIV-negative), and EMVI has is acknowledged as an important risk factor for systemic recurrence, local recurrence and death. Additionally, EMVI status influences the need for pre- and post-operative chemoradiation (CRT); which may influence survival outcomes. Aberrant DNA methylation is emerging as a carcinogenic mechanism and potential biomarker in colorectal cancer. This study investigates the association between hypermethylation and EMVI in vivo and in vitro. Firstly, the in vivo associations between hypermethylation, EMVI, and clinical and histopathological outcomes are examined. Secondly, an investigation of the effects of demethylation on invasive colorectal cell lines in vitro aims to illuminate the genetic and cellular mechanisms that underlie methylation-dependent pathological cellular behaviour. Finally, highlighted biologic mechanisms are investigated in vivo to discover if there is an association with EMVI and survival outcomes. By these means the axis of association between hypermethylation, EMVI, and clinical outcomes is investigated. The investigation is conducted within the framework of consensus molecular subtyping in colorectal cancer, and in concordance with current methodologies of assessing DNA methylation status. The primary findings demonstrate that EMVI is associated with hypermethylation in vivo, but that there is no direct correlation between hypermethylation and disease-free (DFS) or overall survival (OS). In vitro, demethylation of hypermethylated colorectal cancer cells, by means of established demethylating agent 5-azacytidine and putative demethylator RRx-001, reduces their propensity to migrate and invade. Demethylation in vitro is also associated with changes in the expression of the metalloproteinases involved in the metabolism of the basement membrane and the epithelial-to-mesenchymal transition and tumour metastasis, notably MMP2 and TIMP2. Changes in expression were confirmed at transcriptomal and proteomic levels in response to demethylation. In vivo, MMP2 expression was shown to be statistically significantly associated with EMVI, DFS, and OS, and was also independently predictive of EMVI, raising the possibility that it could act as a diagnostic and predictive biomarker in rectal cancers. These findings indicate a mechanistic association between hypermethylation and EMVI, mediated by methylation-dependent expression of metalloproteinases. Metalloproteinase expression, specifically MMP2, may act as a potential biomarker for EMVI and correlates to survival outcomes in rectal cancer

    Systematic review of prognostic importance of extramural venous invasion in rectal cancer

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    AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pubmed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future

    A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

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    Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Results: Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer

    Tumor deposits in colorectal cancer: improving the value of modern staging - a systematic review and meta-analysis

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    PURPOSE: Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TD) in staging remains under debate. We have assessed the relation of TD with metastatic pattern, to evaluate whether TD might add significant new information to staging. METHODS: We performed a systematic literature search focused on the role of TD in CRC. Studies with neoadjuvant treated patients were excluded. Data on stage, histological factors and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TD, lymph node metastases (LNM) and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. RESULTS: Of the 10,106 included CRC patients 22% presented with TD. TD are invariably associated with poor outcome. The presence of TD was associated with the presence of LNM and EMVI. In a pair wise comparison, the effects of TD were stronger than both LNM and EMVI. In the logistic regression model, TD in combination with LNM is the strongest predictor for liver (odds ratio (OR) 5.5), lung (OR 4.3) and peritoneal metastases (OR 7.0). The presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. CONCLUSION: We have shown that TD are not equal to LNM or EMVI, with respect to biology and outcome. We lose valuable prognostic information by allocating TD into nodal category N1c and only considering TD in the absence of LNM. Therefore, we propose that the number of TD should be added to the number of LNM to derive a final N stage
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