LETTER TO THE EDITOR High Ligation of Inferior Mesenteric Artery: A Standard Procedure for Colorectal Cancer? The level of ligation of inferior mesenteric artery (IMA) in patients with colon or rectal cancer in open or laparoscopic surgery has been controversial. In a recent cross-sectional survey among high-volume surgeons, 69% perform high ligation of the IMA and 72% laparoscopic proctectomy. 1 Although standardization of colorectal resection with high ligation of IMA is a safe procedure and the operating time is not longer for experienced surgeons, there has been criticism that it is an overtreatment, requires mobilization of splenic flexure to prevent risk of anastomosis, and has limited benefit in recurrence-free and overall survival. In the March issue of Annals of Surgical Oncology, Kang and colleagues 2 evaluated the prognostic significance of lymph node metastasis at the root of IMA. Among 625 patients with sigmoid colon and rectal cancer who under- went complete resection (R0) with IMA high ligation for stage III disease, 33 patients (5.3%) had node metastasis at the IMA root (IMA-positive group) and 592 (94.7%) had no metastasis at IMA (IMA-negative group). The 5-year disease-free survival rate was 31.9% in the IMA-positive group and 69.4% in the IMA-negative group (P \ 0.001). In multivariate analysis, presence of IMA lymph node metastasis was an independent risk factor for systemic recurrence and para-aortic nodal recurrence. The authors conclude that this high recurrence risk should be consid- ered when planning multimodal treatment. This study provides further evidence for the worse sur- vival of patients with IMA lymph node metastasis. However, the retrospective, histopathological, examina- tion-based selection of stage III patients is a subject of bias, because the preoperative or intraoperative prediction rate of IMA node metastasis is suboptimal and this rate will be even lower for stage II patients than the 5.3% for stage III in this study. Respectively, even lower will probably be a potential survival benefit of IMA high ligation. Moreover, neoadjuvant (preoperative) chemoradiation therapy for rectal cancer can further reduce the low incidence of IMA node metastasis and the need for IMA high ligation. Despite the relatively small benefit of high ligation of IMA during colon or rectal resection for preventing IMA node recurrence and reducing mortality, the absence of accurate prediction of IMA node status may justify this standardized procedure with splenic flexure mobilization in high-volume hospitals. Although prospective, randomized trial is the best tool to establish whether high or low liga- tion of IMA should be performed, the low rate of IMA node metastasis is a problem for patients’ enrollment for a sufficient sample size and statistical power. Although standardization of surgery and adjuvant che- motherapy for colon cancer or chemoradiotherapy for rectal cancer has improved survival, recurrence in stages II and III remains a challenge. After initial excitement with targeted therapy, neither cetuximab nor panitumumab have been proven effective in the adjuvant setting even if cetuximab is administered in genotyping-based selected patients with wild-type KRAS status. 3 Considering the latest cancer genome data which reveals the high complexity and heter- ogeneity of solid cancer, including colorectal cancer, the inefficacy of cetuximab is not surprising. More sophisticated approaches and models are now being developed based on advances in massively parallel sequencing technology and systems biology approaches to understand structural varia- tion and functional deregulation of human genome that drive tumorigenesis and metastasis. This important translational medicine progress may lead to novel, more effective com- binations of anticancer drugs, for improving patients’ oncological outcomes. 4–11 Theodore Liakakos, MD Third Department of Surgery, University of Athens, School of Medicine, Attikon University Hospital, Chaidari, Athens, Greece e-mail: theodlia@otenet.gr Published Online: 2 July 2011 Ó Society of Surgical Oncology 2011 CONFLICT OF INTEREST The authors declare no conflict of interest. REFERENCES 1. Augestad KM, Lindsetmo RO, Reynolds H, et al. International trends in surgical treatment of rectal cancer. Am J Surg. 2011;201(3):353–7, discussion 357–8. Ann Surg Oncol (2011) 18:S240–S241 DOI 10.1245/s10434-011-1883-0