The complexity of the count: considerations regarding lymph node evaluation in colorectal carcinoma

In patients with colorectal carcinoma, studies have reported improved survival with increasing numbers of retrieved lymph nodes. These findings are puzzling, as increased node sampling was not correlated with significant change in disease staging. Although the physiologic processes underlying this correlation between number of lymph nodes sampled and survival remain unknown, the reported correlation has caused modifications to clinical and non-clinical practices. Herein, we review the literature and discuss potential etiologies responsible for the observed increased survival statistics. Literature regarding colorectal lymph node anatomy, molecular aspects of colorectal cancer, changes in tumor characteristics and utilization of lymph node sample numbers are evaluated. In addition, we present the mathematical concepts available for probabilistic prediction of diagnostic confidence based upon sample size. From evaluation of the aggregate literature, certain facts emerge which are not easily identified within the individual studies. Colorectal carcinoma appears to encompass a number of individual disease entities with different physiologic characteristics and likelihoods of metastasis. In addition, it appears the improved survival is likely multifactorial including effects from intrinsic tumor biology and tumor-host interactions along with ever changing clinical practices. Finally, because lymph node count is dependent on a number of variables and is correlated, but unlikely to be causally associated with survival, use of this number as a quality indicator is unwarranted. Based on statistical considerations, the current recommended goal of 12-15 recovered lymph nodes without evidence of metastatic disease provides approximately 80% negative predictive value for colorectal carcinoma metastasis.