The first description of a laparoscopic operation for colon cancer was published in 1991 [25], and many studies, including some large prospective multicenter trials, have proven its short-term safety and efficacy and long-term prognosis for treating colorectal malignant disease [1–4]. Hohenberger et al. [5], who recently identified the concept of CME in colon cancer surgery, proposed that CME was superior to traditional surgery in terms of 5-year cancer-related survival. This surgical technique is based on oncologic resection with careful dissection of the mesocolon along the embryological tissue planes, resulting in a colon and mesocolon specimen lined by intact fascial coverage of the tumor and containing all blood vessels, lymphatic vessels, lymph nodes, and surrounding soft tissue, which may contain disseminated cancer cells. It has also been shown that transecting the supplying vessels at their origin and removing the entire mesocolon lead to crucial surgical planes for curative colonic resection [5, 26, 27]. Excision of specimens with an intact mesocolon has been found to be associated with better survival rates compared with excision of specimens with a defective mesocolon [27, 28].
There are two main approaches that have been reported in the literature regarding LRH: the LM and ML approaches. However, the LM method is usually performed in open surgery. To date, there have been several reports describing the feasibility of the ML approach [8–16]. These reports comprise two multimedia articles [9, 11], five retrospective non controlled studies [10, 12–15] and two retrospective control studies [8, 16] that involved 104, 16, 3, 27, 35, 32, 172, 79 and 8 cases. In terms of its technical efficiency, short convalescence and acceptable short-term oncologic results, the European Association for Endoscopic Surgery (EAES) consensus states that the ML technique should be the preferred approach for laparoscopic colon dissection [13, 29]. In 2016, Zou et al. and Li et al. from Guangdong Provincial Hospital of Traditional Chinese Medicine were the first to report the feasibility of the CC approach for right sided colon cancer [17, 30, 31].
In terms of the common ML approach, the primary oncologic advantages are the early vessel division and the “no touch” dissection. In 1968, Turnbull et al [32] retrospectively reported greatly improved survival rates using “no touch” techniques (5-year survival rates for curable colon cancer, 68.85% vs. 52.13%) and suggested that conventional manipulative resection techniques for cancers of the colon should be abandoned. Hayashi et al. [33] reported that the “no touch” technique could prevent cancer cells from being shed into the portal circulation. The vessels and mesenteric division prior to tumor-containing bowel mobilization could minimize cancer cell spread though the draining vessels. In other words, the value of the “no touch” technique is debated, and the one randomized study on this topic indicated no advantage to support the routine use of the technique [34]. Second, in terms of surgical skill, the longer the lateral abdominal wall attachments of the colon are preserved, the better the exposure and the easier the dissection. As the ascending colon is fixed to the right lateral wall, counter traction can be applied to the mesentery, which facilitates mesenteric dissection. Another advantage of the ML approach is the completeness of D3 lymphadenectomy. Early separation of the white line of Toldt resulted in the distortion of colonic anatomic landmarks and an increase in colon redundancy, which evidently hinders upcoming lymphadenectomy procedures. The ML approach along the vascular anatomy (superior mesenteric vessels) can lead to more complete D3 lymphadenectomy. In the LM approach, vessel ligations are usually performed on the right side of the superior mesenteric vein (SMV), while for the ML approach, total exposure of the superior mesenteric artery (SMA) and SMV is typical. The ML approach, however, involves several limitations. For overweight patients, the mesocolon may be too thick for the identification of vessel landmarks, and it is difficult for inexperienced surgeons to enter Toldt’s space accurately. The ML approach encounters numerous variations in vessels and anatomic complexity around the pancreatic area and is thought to be a more complex and demanding procedure with longer learning curves compared with other approaches [35–37]. There is also a concern of increased bacterial contamination because early ligation of the vasculature lengthens the ischemic time of the colonic segment, but this remains theoretical at this point.
For a better operation and shorter learning curves, Zou et al. and Li et al. proposed the CC approach in 2016 [17, 30, 31]. With this approach, it is easy to enter and explore the proper plane by following the fine areolar tissue, which may help reduce potential injuries to retroperitoneal structures such as the ureter and gonadal vessels. The vascular pedicles are divided after they are exposed dorsally, which may be performed safely and easily. In either the LM approach or ML approach, the peritoneum is incised at the lower edge of the ileocolic pedicle, and the lymph nodes at the root of the pedicle (No. 203 lymph nodes) cannot be swept radically in some cases, especially in patients whose ileocolic artery crosses the SMV dorsally. Therefore, if the ileocolic artery and right colonic artery are cut on the right side of the SMV, 3.2–5.8% of positive lymph nodes along the SMV/SMA (root nodes) are left behind [38]. For dissection with the CC approach, Toldt’s space is entered first, and the lymph nodes at this point can be dissected easily and completely via a joint view of the dorsal aspect and ventral aspect. For inadvertent and even massive bleeding, this approach can be managed easily and promptly, as the retroperitoneal space has been dissected and the courses of the right colic artery, veins, gastrocolic trunk, and SMV have been uncovered previously in some cases. This can be helpful for decreasing the conversion rate. The CC approach is characterized by prior retroperitoneal treatment, and the tumor-bearing area is less manipulated with this approach than with the LM approach.
In our study, there was no intraoperative mortality. The median surgical time (ST) was longer in the ML group (206.50 min (178.75, 226.25)) than in the CC group (170.00 min (145.00, 210.00)), which was statistically significant (p=༜0.001). The mean blood loss (BL) was 80.00(50.00, 100.00)ml in the CC group and 50.00 (50.00, 100.00) ml in the ML group, which was not statistically significant. These results are comparable with the outcomes of the ML approach reported by Feng et al. (ST: 2.5 (2–4) h; BL: 80(50–300) mL) [10], Han et al. (ST: 133 ± 36 min, BL: 94 ± 34 ml) [39], and Wang et al. (ST: 113.5 ± 34.4 min, BL: 74.2 ± 28.1 mL) [15]. Undergoing the CC approach, Li et al from our department reported that the mean ST was 178.3 min (range, 150–215), and the mean BL was 81.6 ml (range, 50–200) [17]. All the above studies [10, 17, 39] used the CME procedure. The ST in the CC group in our study was shorter, the possible reason is that the CC approach has more advantages in the treatment of blood vessels as the retroperitoneal space has been dissected. In previous studies using conventional colonic surgery, postoperative complication rates have been reported to range from 9.0–22.5% [4, 40, 41]. Several recent studies using CME have shown that postoperative morbidities range from 5.7–19.7% [5, 10, 42]. For right colon cancer using the ML approach, morbidity ranges from 8.6–16.3% [10, 15], and it was 7.5% for the CC approach in a previous study [17]. In this study, the rates of postoperative morbidity were 13.64% in the CC group and 15.60% in the ML group. Postoperative ileus was a major complication in the CC group; however, postoperative bleeding mostly occurred in patients in the ML group.
The range of resection and dissection of lymph nodes is a key factor in terms of the radical principles of oncology and can influence the long-term outcome of colon cancer [43–45]. The mean number of harvested lymph nodes in our study was 16.50(14.00, 21.25)in the CC group and 18.00༈15.00, 22.00༉in the ML group. The results were roughly in accordance with the outcomes of other studies with the use of the ML and CC approaches [10, 16, 17, 39]. The mean number of positive harvested lymph nodes was 0༈0, 2.00༉in the CC group and 0༈0, 1.50༉in the ML group in our study. Kanemitsu et al. reported that the mean positive node yields were 1.3 to 1.7 for the intermediate nodes and 1.3 to 1.5 for the main nodes in stage I to III right colon cancer [46]. In particular, for stage III right colon cancer, in the study by Kobayashi et al, the mean number of lymph nodes harvested was 20 ± 12, and the median number of positive nodes was 3 (range 1–23) [47].
For postoperative recovery with the ML approach, Feng et al reported that the postoperative flatus recovery time was 2 (1–4) days and the liquid intake time was 3 (3–5) days. Patients could start ambulation 3 (2–7) days after surgery, and the total hospital stay was 12 (6–20) days [10]. Another study by Han et al showed that the average times for the passage of flatus, liquid food eating, and hospitalization were 2.1 ± 0.7, 3.2 ± 0.5, and10.4 ± 2.7 days, respectively [39]. A meta-analysis conducted by Li et al revealed that the LM approach required a shorter postoperative flatus recovery time than both the ML approach with a WMD of 1.40 (95% CI: 0.13 to 2.67, P < 0.05) and the CC approach (WMD = -1.25,95% CI: -1.90 to -0.61, P < 0.05). The length of hospital stay for the LM approach was shorter than that for the ML approach (WMD = 0.29, 95% CI: 0.08 to 0.50, P < 0.05) [37]. For the CC approach, the mean postoperative hospital stay was 5.7 days (range, 5–8) in the study by Li et al [17]. In our study, the time to oral intake in the CC group was shorter than that in the ML group (3.00(1.00, 4.00)versus 3.00༈2.00, 5.00༉days, p = 0.007); however, there were no statistically significant differences between these two groups in terms of the time to first flatus, time to pull out urine and drainage tube.
Survival is still controversial. Lacy et al. [3] showed advantages of laparoscopic over open surgery in terms of 5-year cancer related survival for stage I to III colon cancer. The results of the randomized controlled trials of COLOR (5-year prognosis) [4], COST (5-year prognosis) [1] and MRC CLASSIC (3-year prognosis) [2] suggested that RFS and OS were similar between these two groups for stage I to III colorectal cancer. For right sided colon cancer, when OS was compared between the laparoscopic and open groups, no difference was found [48]. A similar tendency was observed for stage I to III patients in terms of the rates for RFS and OS; the median follow-up period was 83 months in the laparoscopic group and 105 months in the open group [40].
There have been several studies on the prognosis of LRH for right sided colon cancer. In a study by Baca et al., the 5-year OS rate in 48 patients who underwent surgery with curative intent was 75%for stages I to III [49]. In another study, the cumulative OS of all stages at 12, 36, 60 and 72 months was 97.18%, 83.73%, 70.37%and 68.99%, respectively, and the RFS was 98.73% (12 months), 87.81% (36 months) and 80.17% (60 months) [39]. According to different stages, the 5-year OS rates of patients with stage I (19.7%), II (41.9%) and III (38.4%) cancer were 94.5%, 87.6% and 79.2%, respectively, and the 5-year RFS rates were 100.0%, 94.5% and 85.0% [46]. The stratified 5-year survival rates in patients with stage II and IIIA/B and in the subgroup of stage IIIC patients with negative apical nodes were 88.7%, 72.4%, and 71.4%, respectively; however, stage IIIC patients with positive apical nodes showed poor survival (27.7%). According to the multivariate analysis, a “non-mesocolic” plane of resection, positive N3 apical nodes and CEA levels > 5 ng/dL were found to be independent prognostic factors [50]. In Cho et al.’s study, modified CME resulted in a high 5-year OS rate of 84.0% and 5-year RFS rates of 85.8% and 73.0% in all patients and patients with stage III disease, respectively [51]. These results are comparable with the survival outcomes reported by the Erlangen group (5-year DFS of 89% for all stages and ≥ 70.0% for stage III disease), and stage III disease, postoperative complications, age ≥ 60 years, and minimally invasive surgery were found to be independent prognostic factors [26]. For the mid-term period, in the study by Wang et al., the 3-year RFS and OS rates were 81.7% and 89.1%, respectively. The rates of RFS and OS were significantly higher for stages I and II than for stage III (P < 0.05) and for stages IIIA/B than for stage IIIC (P < 0.05) [15]. In our study, 5 years OS rates were 75.76% in the CC group and 82.57% in the ML group (HR 0.654, 95% CI 0.336–1.273, p = 0.207); 5 years PFS rates were 80.30% in the CC group and 85.32% in the ML group (HR 0.683, 95% CI 0.328–1.422, p = 0.305). Our results are comparable with the survival outcomes reported in the study by Kanemitsu et al [46].
The recurrence rate is a crucial indication for evaluating the long-term outcomes of surgery. Some researchers have shown that the 5-year recurrence rate of LRH varies from 14.7–29.5% [39, 50, 51]. Generally, it should be subdivided into 5-year local recurrence and systemic recurrence for patients with stage I to III disease. The local recurrence for stages I to III varies from 2.8–6.8% [39, 50, 51]; the systemic recurrence for stages I to III varies from 11.9–22.7% [39, 50, 51]. As demonstrated in our results, 13 cases were distant metastasis and 3 cases were local recurrence in the ML group; 11 cases were distant metastasis and 2 cases were local recurrence in the CC group for stages II to III during the 5-year follow-up period.
Despite the limitations inherent to a retrospective study in a single institute, our findings support the concept that the CC approach can be safely performed through a laparoscopic technique with a satisfactory 5-year prognosis compared to the traditional ML approach. Central ligation of supplying vessels in laparoscopic surgery for right sided colon cancer is difficult for novice surgeons. This study does not address the issue of the learning curve for this technique. Furthermore, we did not compare the mesenteric integrity of specimens between these two different surgical approaches.