The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-analysis

Iddings, D.; Alipour, Ahmad; Elashoff, David; Bilchik, Anton J.

doi:10.1245/s10434-006-9120-y

Cited by 119 publications

(145 citation statements)

References 39 publications

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“…In spite of the potentially curative resection, about 15-30% of patients with stage II disease will eventually develop recurrent locoregional disease or distant metastases within 5 years (Koebrugge et al 2011). Possibly, other high-risk factors can influence or predict the outcome in patients with stage II colon cancer, and further research seems warranted (Iddings et al 2006, van Schaik et al 2009, Bilchik et al 2010. The elucidation of the molecular biology of cancer cells is currently being exploited to develop potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Huang

Chen

Chiu

et al. 2013

Endocrine-Related Cancer

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Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been shown to affect cancer cell metastasis and invasion. However, the molecular mechanisms underlying GDNF-induced colon cancer cell migration remain unclear. GDNF is found to be positively correlated with malignancy in human colon cancer patients. The migratory activities of two human colon cancer cell lines, HCT116 and SW480, were found to be enhanced in the presence of human GDNF. The expression of vascular endothelial growth factor (VEGF) was also increased in response to GDNF stimulation, along with VEGF mRNA expression and transcriptional activity. The enhancement of GDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Our results also showed that the expression of VEGF receptor 1 (VEGFR1) was increased in response to GDNF stimulation, whereas GDNF-induced cancer cell migration was reduced by a VEGFR inhibitor. The GDNF-induced VEGF expression was regulated by the p38 and PI3K/Akt signaling pathways. Treatment with GDNF increased nuclear hypoxia-inducible factor 1 a (HIF1a) accumulation and its transcriptional activity in a time-dependent manner. Moreover, GDNF increased hypoxia responsive element (HRE)-containing VEGF promoter transcriptional activity but not that of the HRE-deletion VEGF promoter construct. Inhibition of HIF1a by a pharmacological inhibitor or dominant-negative mutant reduced the GDNF-induced migratory activity in human colon cancer cells. These results indicate that GDNF enhances the migration of colon cancer cells by increasing VEGF-VEGFR interaction, which is mainly regulated by the p38, PI3K/Akt, and HIF1a signaling pathways.

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Section: Discussionmentioning

confidence: 99%

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Huang

Chen

Chiu

et al. 2013

Endocrine-Related Cancer

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“…A média de idade encontrada nesse estudo foi de 61 anos, próxima à média de idade encontrada em outras séries 1,5,6,8,9,24,27,28 , sendo o risco desse câncer tanto maior quanto maior a faixa etária, uma vez que mais de 50% dos casos ocorrem em indivíduos com mais de 50 anos 29 .…”

Section: Discussionunclassified

“…Metástases linfonodais são o fator prognóstico mais importante no CCR, de forma que a investigação patológica, além da avaliação histológica de rotina de linfonodos, pode identificar maior número de pacientes com alto risco de recorrência 28 .…”

Section: Média De Gânglios Dissecados Média De Gânglios Positivosunclassified

Fatores de mau prognóstico nas peças operatórias de pacientes submetidos ao tratamento cirúrgico do câncer colorretal

Volpato

Koch

2008

Rev bras. colo-proctol.

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“…Both are circumstances that limit their widespread use. Another advanced technique, the application of immunohistochemical staining methods for the detection of micrometastes is expensive and failed to prove a significant difference concerning 3-year disease-free survival in a meta-analysis performed by Iddings et al 18 In contrast confirmation of micrometastes using RT-PCR showed a significant smaller 3-year disease-free survival and reduced overall survival in positive cases.…”

Section: Discussionmentioning

confidence: 99%

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

et al. 2007

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Adequate lymph node assessment in colorectal cancer is crucial for prognosis estimation and further therapy stratification. However, there is still an ongoing debate on required minimum lymph node numbers and the necessity of advanced techniques such as immunohistochemistry or PCR. It has been proven in several studies that lymph node harvest is often inadequate under routine analysis. Lymph nodes smaller than 5 mm are especially concerning as they can carry the majority of metastases. These small, but affected lymph nodes may escape detection in routine analysis. Therefore, fat-clearing protocols and sentinel techniques have been developed to improve accuracy of lymph node staging. We describe a novel and simple method of ex vivo methylene blue injection into the superior rectal artery of rectal cancer specimens, which highlights lymph nodes and makes them easy to detect during manual dissection. Initially, this method was developed for proving accuracy of total mesorectal excision. We performed a retrospective study comparing lymph node recovery of 12 methylene blue stained and an equal number of unstained cases. Lymph node recovery differed significantly with average lymph node numbers of 2777 and 1474 (Po0.001) for the methylene blue and the unstained group, respectively. The largest difference was found in size groups between 1 and 4 mm causing a shift in size distribution toward smaller nodes. Metastases were confirmed in 21 and 19 lymph nodes occurring in five and four cases, respectively. Hence, we conclude that methylene blue injection technique improves accuracy of lymph node staging by heightening the lymph node harvest in rectal resections. In our experience, it is a very simple time and cost effective method that can be easily established under routine circumstances.

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The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-analysis

Cited by 119 publications

References 39 publications

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Fatores de mau prognóstico nas peças operatórias de pacientes submetidos ao tratamento cirúrgico do câncer colorretal

Methylene blue injection into the rectal artery as a simple method to improve lymph node harvest in rectal cancer

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