Predictors of Lymph Node Count in Colorectal Cancer Resections

Morikawa, Teppei; Tanaka, Noriko; Kuchiba, Aya; Nosho, Katsuhiko; Yamauchi, Mai; Hornick, Jason L.; Swanson, Richard S.; Chan, Andrew T.; Meyerhardt, Jeffrey A.; Huttenhower, Curtis; Schrag, Deborah; Fuchs, Charles S.; Ogino, Shuji

doi:10.1001/archsurg.2012.353

Cited by 35 publications

(32 citation statements)

References 56 publications

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“…Tumor location appeared to consistently predict a sufficient number (≥12) of nodes, which is in line with recent reports (22,23). However, when the factors affecting the total number of harvested LNs were assessed and adjusted for age and sex, MSI was the only significant factor, explaining 11% of the change in the regression model.…”

Section: Discussionsupporting

confidence: 89%

“…Both MSI and proximal tumor location appear to be associated with a higher LN harvest, both independently and in combination. This relationship has been demonstrated in different populations with the use of various cutoffs to determine the appropriate nodal count (11)(12)(13)23). In contrast to these studies, a Canadian study found no significant difference between the effects of MSI and MSS on LN harvest in 168 selected stage III colon cancer patients (27).…”

Section: Discussionmentioning

confidence: 98%

“…However, the study used the median and mean node counts as a cutoff, rather than the guideline of ≥12 nodes suggested for clinical decision-making. In contrast, the relationship between MSI and a larger number of harvested nodes has been demonstrated in study populations in Norway (11), France (13), the Netherlands (12), and the U.S. (23).…”

Section: Discussionmentioning

confidence: 98%

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Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Berg

Guriby

Nordgård

et al. 2013

Mol Med

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Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I-III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni-and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5-5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2-4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 98%

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Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Berg

Guriby

Nordgård

et al. 2013

Mol Med

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“…Our results are in total agreement with similar recent studies suggesting that tumor location, tumor grade [13], stage [14][15][16] and size is significantly impacting the number of identifiable LNs [17]. Shen et al have recently reported that number of harvested LNs is most significantly associated with tumor location (right sided vs left sided cancer), patient age and length of resected specimen [12].…”

Section: Discussionsupporting

confidence: 93%

Variables Impacting Lymph Node Recovery in Colectomy Resection Specimens Removed for Colorectal Adenocarcinoma

Schafer¹,

Kimler

McGregor³

et al. 2013

TOPATJ

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Abstract:Background: Recent data suggest that a higher number of nodes evaluated in colectomy specimens for colorectal adenocarcinoma is associated with increased survival. Recommendations mandate the harvesting of at least 12 nodes in colectomy specimens for adequate assessment. Recent studies argue that the above association is complex and is uncontrolled for a variety of variables.Objective: The study's objective is to evaluate several factors that impact the harvesting of lymph nodes in colectomy specimen. Patients:We reviewed 306 colectomy specimens from 2 academic medical centers, 177 from Kansas University Medical Center (KUMC) and 129 from the Kansas City Veterans Affairs Medical Center (VAMC) from 2000 to 2007.Design: Factors evaluated included tumor size, grade, stage, site, number of positive nodes and length of colectomy segment removed. We compared the number of nodes removed at the 2 institutions and whether individual surgeons had an impact on the number of harvested nodes.Results: Harvesting at least 12 nodes is correlated with larger tumor size, higher grade and stage and specimens longer than 21 cm. More nodes were harvested from the right colon (mean=13 nodes), followed by descending (12 nodes), transverse and rectosigmoid (10 nodes each). Number of positive nodes correlated with tumor grade, but not with tumor site, size, linear length of specimen or whether 12 nodes were harvested.Cases from the VAMC were more likely to harvest 12 nodes compared to KUMC. It was noted that 2 of 10 surgeons at the VAMC performed 76% of all surgeries. There were 21 surgeons at KUMC; none performed more than 12% of the cases. Conclusion:Number of harvested nodes is related to other prognostically significant parameters primarily related to tumor biology. The potential impact of surgeon's experience and the type of surgery performed needs further evaluation.

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“…The role of MCs has been broadly studied both in animal and human cancers, such as MC tumors, head-and-neck, gastric, colorectal, lung and cutaneous malignancies, indicating that MC density is highly correlated with the extent of tumor angiogenesis [9,10,11,12]. In gastrointestinal tumors, the presence of lymph node metastases is one of the most important determinants of prognosis, and tumor node metastasis (TNM) is the most commonly used staging system [13,14,15]. In the present study, we have evaluated various correlations between different parameters such as MCs positive to tryptase (MCPT) in tumor tissue, the number of metastatic lymph nodes harvested or tryptase activity in lymph nodes in a series of 41 gastrointestinal cancer patients with stage T 3-4 N 2a-b M₀ (by the American Joint Committee on Cancer, AJCC, for colorectal cancer, 7th edition) and T 3 N 2-3 M₀ (by AJCC for gastric cancer, 7th edition) by means of immunohistochemistry and imaging methods.…”

Section: Introductionmentioning

confidence: 99%

Mast Cell Positivity to Tryptase Correlates with Metastatic Lymph Nodes in Gastrointestinal Cancer Patients Treated Surgically

et al. 2013

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Background: Angiogenesis has been found to be a reliable prognostic indicator for several types of malignancies. Tryptase is a serine protease stored in mast cell (MC) granules, which plays a role in tumor angiogenesis. MCs can release tryptase following c-Kit receptor activation. Method: In this study, immunohistochemistry, image analysis methods and clinical aspects were employed in a series of 41 gastrointestinal cancer patients with stage T_3-4N_2a-bM₀ (by the American Joint Committee on Cancer, AJCC, for colorectal cancer, 7th edition) and T₃N_2-3M₀ (by AJCC for gastric cancer, 7th edition) to evaluate the possible correlation between MCs positive to tryptase (MCPT) in tumor tissue and the number of metastatic lymph nodes harvested. Results: Data demonstrated a positive correlation between MCPT in tumor tissue and the number of metastatic lymph nodes; the validity of these data needs confirmation in larger patient cohorts. Conclusion: This is the first report considering MCPT in tumor tissue as a potential tool for a valid indication of the type of surgical treatment and its radicality, and it might be considered for the prognosis of patients before radical surgical treatment. Our pilot data need confirmation in a larger patient cohort.

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Predictors of Lymph Node Count in Colorectal Cancer Resections

Cited by 35 publications

References 56 publications

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers

Variables Impacting Lymph Node Recovery in Colectomy Resection Specimens Removed for Colorectal Adenocarcinoma

Mast Cell Positivity to Tryptase Correlates with Metastatic Lymph Nodes in Gastrointestinal Cancer Patients Treated Surgically

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