Laparoscopic complete mesocolic excision with D3 lymph node dissection for right colon cancer in elderly patients

Complete mesocolic excision (CME) with D3 lymph node dissection is considered an oncological surgery for right colon cancer. However, there is still controversy for extensive oncological surgery in elderly patients. The aim of this study is to evaluate the safety and oncological outcomes of laparoscopic CME with D3 lymph node dissection for right colon cancer in elderly patients. Patients who underwent laparoscopic right colectomy, from 2004 to 2014, were divided into Groups A (age ≥ 70 years, n = 80) or B (age < 70 years, n = 127). Short and long-term outcomes were analysed. Basic demographics and short-term surgical outcomes were similar between groups. Among pathological outcomes, the mean number of harvested lymph nodes was significantly less in Group A. Adjuvant chemotherapy refusal rate was significantly higher in Group A. Overall and recurrence-free survival were similar between groups. We found laparoscopic CME with D3 lymph node dissection is a safe and feasible surgical option for right colon cancer in elderly patients.

www.nature.com/scientificreports/ n = 80), or Group B, which consisted of younger patients (age < 70 years, n = 127). Demographic and operational data, pathologic outcomes, postoperative short-term clinical outcomes, overall survival, and recurrence-free survival were analysed between the two groups. Patients in whom R1, R2 resection or synchronous multiple cancers, combined organ resection, and stage IV colon cancer were excluded from this study.
Surgical procedure and D3 Lymph node dissection. D3 lymph node dissection was defined as removal of main lymph nodes at the root of the feeding vessels (ileocolic vessels and the right branch of the middle colic artery or middle colic artery), followed by ligation of vessels at the origin site ( Fig. 1).
Postoperative complications. Intraoperative major complications included massive bleeding, which required transfusion, and organ injury, which required surgical treatment. The postoperative surgical complications in accordance with Clavien-Dindo classification ≥ 2 were investigated. These included surgical site infection, ileus, anastomotic leakage, bleeding, organ dysfunction, and sepsis.
Statistical analyses. Continuous variables such as age, operation time, amount of bleeding, and number of harvested lymph nodes are presented as mean ± standard deviation. Categorical variables, such as sex and surgical complication ratio, are expressed as frequencies or ratios. Student's t-test was used to compare continuous variables, whereas the categorical variables were compared using the Chi-square test. Among categorical variables, the American Society of Anesthesiologists (ASA) score, intraoperative complication ratio and conversion ratio, and mortality ratios were compared using Fisher's exact test, as appropriate. Survival was analysed using the Kaplan-Meier method, and the curves were compared using the log-rank test. A P value of ≤ 0.05 was considered significant. All methods were performed in accordance with the relevant guidelines and regulations, and this study was approved by the Institutional Review Board of Incheon St. Mary's Hospital (OC18RESI0020), which also waived the requirement for informed consent due to the retrospective nature of the study.

Results
The demographic features of Groups A and B are shown in Table 1. The mean age of Groups A and B was 76.3 years and 57.9 years, respectively (P = 0.000). No significant differences were observed between the two groups in terms of sex, body mass index, and ASA physical status score. Table 2 shows no significant differences between the two groups regarding operation details. Major intraoperative complications such as duodenal injury and bleeding due to major vessel injury occurred in 3 cases in Group A and 4 cases in Group B. The open conversion ratio was 2/80 (2.5%) and 3/127 (2.4%) in Groups A and B, respectively. The reasons for open conversion were large tumour size, congenital vascular anomaly, and bleeding due to major vessel injury. There were no significant differences between the two groups regarding pathologic TNM stage. The number of mean harvested lymph nodes was less in Group A than in Group B (25.3 ± 8.2 vs 31.4 ± 16.7, P = 0.001). No pathologic  www.nature.com/scientificreports/ differences were noted regarding proximal resection margin, distal resection margin, tumour size, lymphatic, vascular, or perineural invasion between the two groups ( Table 3). The postoperative clinical outcomes between the two groups are shown in Table 4. Postoperative hospital stay, diet start day, and flatus passing day were not significantly different between the two groups. Clavien-Dindo ≥ 2 postoperative complications occurred in 13 cases in Group A and 16 cases in Group B. These complications included postoperative bleeding, anastomotic leakage, ileus, acute renal failure, and pancreatitis. A single occurrence of mortality was recorded in Group A due to pulmonary thromboembolism. Refusal rate for adjuvant chemotherapy was significantly higher in Group A than in Group B (12/44 vs 5/77, P = 0.002). Figures 2 and 3 show the survival analysis between the two groups. Overall survival and recurrence-free survival rates were not significantly different between the two groups according to each stage and all stage groups.

Discussion
CME along with central vascular ligation of feeding vessel, commonly known as D3 lymph node dissection, was applied to colon cancer in a similar manner as total mesorectal excision for rectal cancer, in which embryologic tissue planes are resected along the entire enveloped mesocolon. This technique has been found to improve   www.nature.com/scientificreports/ www.nature.com/scientificreports/ long-term survival and reduce local recurrence compared with previous performed procedures and is now being considered an extensive oncological surgical option for right colon cancer surgery 10,11 . One of the most important prognostic factors in colorectal cancer is the nodal status. The presence of lymph node metastasis is a main determinant for adjuvant chemotherapy and a predictor of disease-free and overall survival [12][13][14] . Kotake et al. have reported that D3 lymph node dissection for pT3 and pT4 colon cancer is associated with a significant survival advantage from a large-scale database. Compared to D2 lymph node dissection, D3 lymph node dissection relatively reduces the risk of death by 18% in terms of the overall survival of patients with pT3 and pT4 colon cancer 15 .
Some previous studies have reported the effectiveness of D3 lymph node dissection, even in early stage colon cancer. Storli et al. reported that compared to the D2 approach, CME with D3 surgical management of colon cancer resulted in significant immediate improvement of 3-year survival for patients with TNM stage I-II tumours as assessed by their overall survival and disease-free survival 16 . This improvement was possibly due to the removal of the micrometastases and skip metastases in D3 lymph node dissection. Removal of micrometastases, which occur without obvious lymph node metastasis, influences the survival of patients with stage I and II colon cancer 17-20 . There is debate regarding the extent of lymph node dissection for colon cancer between young and elderly patients. Egenvall et al. reported that elderly patients tend to be treated with less vigilance in surgical procedure of colon cancer performed than young patients. In particular, right colon cancer stage I-III is less often resected radically 21 . However, our study showed acceptable short-term clinical and long-term oncological outcomes of laparoscopic CME with D3 lymph node dissection in elderly patients compared to young patients. This study covered surgeries over an extended period, up to 10 years, and evolution of technique can affect the outcomes of study. Therefore, we conducted a subgroup analysis on perioperative complication rates, overall and recurrencefree survival between the two groups according to the 2004-2009 or 2010-2014 period. In this subgroup analysis, no difference was noted between the elderly and young patient groups. Specifically, in the 2004-2009 subgroup analysis, the P value of recurrence-free survival between the two groups was 0.326. The P value of overall survival between the two groups was 0.166. Perioperative complication ratio was 7/25 and 9/39 each, and the P value was 0.657. In the 2010-2014 subgroup analysis, the P value of recurrence-free survival between the two groups was 0.146 and the P value of overall survival between the two groups was 0.778. The perioperative complication ratio was 11/55 and 20/88, respectively, and the P value was 0.700. We think that it is important to offer the same standardised surgical resection procedure to all patients, regardless of age.
Laparoscopic CME with D3 lymph node dissection is technically demanding and carries the risk of several complications due to the complex anatomy related to the mesenteric planes and the vascular anatomical variations. Bertelsen et al. reported that CME is associated with more intraoperative organ injuries and severe nonsurgical complications than conventional hemicolectomy 22 . However, several studies reported that laparoscopic D3 lymph node dissection for colon cancer is technically feasible and effective, with surgical results being optimised through a combination of surgical proficiency, institutional case load, and expertise [23][24][25][26][27][28] . In the present study, some intraoperative complications occurred, but most were managed appropriately during operation. The overall complication rate in this study was 16.3% in the elderly group and 12.6% in the younger group, but it was not significantly different.
Adjuvant chemotherapy improved oncological outcomes in locally advanced colorectal cancer and is usually recommended for locally advanced colorectal cancer. However, elderly patients are inclined to refuse adjuvant chemotherapy. Benson et al. reported that approximately 1/3 of elderly patients who had an indication for chemotherapy refused the treatment 29 . In this study, the refusal rate of adjuvant chemotherapy among candidates in the elderly group was 27.3% and was significantly higher than that in the younger group, which was 6.5%. Interestingly, no significant differences were however noted in the overall survival and recurrence-free survival between groups. We thought extensive lymph node dissection might have a favourable impact on oncological outcomes in elderly patients, even in patients who refused adjuvant chemotherapy.
This study has some limitations. First, because we performed D3 lymph node dissection in most of the patients, direct comparisons with D1 or D2 lymph node dissection in the same elderly group could not be made. Second, this study had a retrospective and single-centre design. Additional prospective studies with multiple centres are required to fully evaluate the safety and oncological impact of laparoscopic CME with D3 lymph node dissection in elderly patients with right colon cancer.

conclusion
Our study revealed acceptable short-term clinical outcomes and long-term oncologocical outcomes of laparoscopic CME with D3 lymph node dissection in elderly patients with right colon cancer, despite the high refusal rate of adjuvant chemotherapy. We recommend this procedure as a safe and optimal option for these patients. www.nature.com/scientificreports/