DOI: https://doi.org/10.21203/rs.3.rs-1536633/v2
Development of the midgut is characterized by rapid elongation of the gut and its mesentery, resulting in the formation of the primary intestinal loop, which rotates around an axis formed by the superior mesenteric artery. Eventually, a complex twisted intestinal and mesenteric anatomy is formed by displacement, rotation, and fusion. Therefore, we theoretically believed that the colon and its mesentery should be restored to the simple primitive mesenteric state, and then en bloc resection could be better performed. In the present study, we introduced a surgical technique for laparoscopic complete mesocolic excision (CME) based on the concept of developmental anatomy (DA group), which was successfully performed on 65 patients with right-sided colon cancer. As a control, traditional laparoscopic CME surgery (CME group) was also performed on 65 patients with right-sided colon cancer by the same surgical team at the same time period. Compare with the CME group, patients in the DA group presented with the less blood loss (20.3 ± 10.4 ml vs 34.6 ± 22.2 ml, p < 0.001), the shorter hospital day (6.4 ± 2.2 days vs 7.5 ± 2.2 days, p = 0.007), and the higher lymph node lymph node harvested (48.3 ± 12.7 vs 33.0 ± 11.2, p < 0.001), whereas the oncologic outcomes at 12 months follow-up did not differ significantly. In conclusion, the surgical procedure of CME based on the concept of developmental anatomy is technically safe and feasible for right-sided colon cancer.
Embryologically, the primitive gut is an endoderm-derived organ system, which is subdivided into the foregut, midgut, and hindgut, and the right-side colon is derived from the midgut. A complex twisted intestinal and mesenteric anatomy is formed by displacement, rotation, and fusion [1, 2]. During the development of the right-side colon, the medial and lateral plates of the mesoderm formed the right-side mesocolon and abdominal wall fascia, respectively. Moreover, the neuroectoderm also formed the nerve fascia, which led to the different structures of developmental anatomy during the dorsal separation of the right-side mesocolon.
Complete mesocolic excision (CME) has been accepted as the optimal surgical approach for right-sided colon cancer, resulting in good oncologic outcomes, as well as the standard procedure for colon cancer [3, 4]. However, CME seems a theory of en-bloc resection, and standard CME surgery has been associated with certain technical challenges, especially when performed by inexperienced surgeons. CME surgery is based on the separation of the right-side colon from the gastric, duodenum, pancreas, and left-side colon. From the perspective of embryonic development, the gastric, duodenum and its dorsal mesentery, the pancreas and dorsal pancreatic mesentery, and the greater omentum are derived from the foregut, and the left-side colon is derived from the hindgut while the right-side colon derives from the midgut. Therefore, CME for the right-side colon mainly relies on the separation of the midgut from the foregut and hindgut. In the present study, we proposed a novel surgical procedure for laparoscopic right hemicolectomy based on the concept of developmental anatomy, which was expected a further improvement of CME.
Between April 2020 and April 2021, 65 consecutive patients of right-side colon cancer undergoing laparoscopic complete mesocolic excision based on the concept of developmental anatomy (DA group) in the department of gastrointestinal surgery, Renmin hospital of Wuhan University were included. The inclusion criteria were as follows: (1) Right-side colon cancer was confirmed pathologically by endoscopic biopsy, (2) American Society of Anesthesiologists (ASA) class was 1–3, (3) Laparoscopic radical resection was performed, and (4) No pelvic or distant metastasis was found. This study was approved by the institutional review board of the Renmin Hospital of Wuhan University, and written informed consent was obtained from all patients.
As a control, 65 patients with right-sided colon cancer undergoing laparoscopic traditional CME surgery (CME group) by the same surgical team were also included between April 2020 and January 2021. The perioperative data and oncologic outcomes at 12 months follow-up were collected and analyzed.
The details of the surgical procedures in the DA group are shown in the Supplementary material video. Briefly, patients were first placed in the Trendelenburg position, after which five trocars were inserted (infraumbilical area: 10 mm optic, right lower quadrant: 5 mm, right upper quadrant: 5 mm, left upper quadrant: 10 mm, left lower quadrant: 5 mm). Carbon dioxide was inflated through the intraumbilical trocar, and the pressure was maintained at 15 mmHg. The operating surgeon stood on the patient's left side, with the assistant on the right.
The first step was cephalic dissection, which was the separation of the midgut and foregut, i.e., the separation of the right-side mesocolon from the greater omentum, the mesogastrium, and dorsal mesoduodenum. The extra-omentum approach was preferred, and the greater omentum was selectively preserved because the serosa was not invaded. The dissection plane between mesogastrium and continuous mesentery of the gastric-transverse colon was entered and extended, and the upper mesogastrium and the inferior transverse mesocolon were left intact and smooth (Fig. 1A). And then, the dissection continued downward to the right side of descending duodenum along the mesocolic space between the mesocolon and dorsal mesoduodenum (Fig. 1B). Therefore, the dorsal mesogastrium, transverse mesocolon, and dorsal mesoduodenum were intact.
The second step was the dorsal separation, which included the separation of the midgut and hindgut. After exposing the dorsal aspect of the Treitz ligament, the fusion fascia between the mesointestin and the dorsal right-side mesocolon was separated along the superior aspect of the Treitz ligament (Fig. 1C). And then, the dissection continued upward to the right side of descending duodenum along the mesenteric fused fascia space between the prehypogastric nerve fascia and mesocolon. (Fig. 1D), and the duodenum and its dorsal mesentery were revealed. Further cephalad separation along the dorsal mesentery of the duodenum was performed, naturally extending to the continuous dorsal mesentery of the duodenum-pancreas. Finally, the dorsal dissection met with cephalic dissection. Therefore, the lower prehypogastric nerve fascia, middle mesoduodenum, upper mesopancreas, and right-side mesocolon were intact.
The third step was ventral dissection. A sloping natural fold can be identified by traction to the ileocolic vessels, dissection was performed along the mesenteric fused fascia between the small intestinal and right hemicolon. Finally, the ventral dissection met with dorsal dissection.
The fourth step involved the ligation of intra-mesenteric vessels and the separation of right-side mesocolon from left-side mesocolon. Intra-mesenteric vessels were defined and located within the fused fascia or mesocolic space, which are ligated along the mesenteric fused fascia space regardless of their name (Fig. 1E), and the vascular sheath of the superior mesenteric vein is not damaged. And then, the right-side mesocolon was separated from the left-side mesocolon along the mesocolic space (Fig. 1F), En-bloc resection of the right hemicolon and its mesentery is performed.
All data are presented as mean (± SD) for continuous variables and as frequency (%) for categorical variables. The independent t-test was used for continuous variables, and the Chi-square test or Fisher’s exact test for categorical variables. The survival curves were analyzed by Kaplan–Meier analysis and plotted in R software (version 4.0.3). A p value < 0.05 was considered statistically significant. All statistical analyses were performed with SPSS version 26.0 for Windows (SPSS Inc., Chicago, IL, USA).
No major intraoperative and postoperative complications (Clavien-Dindo grade ≥ 3) were found, while there were 3 cases with minor complications (4.6%) in the DA group, which included 1 case of wound infection, 1 case of diarrhoea, and 1 case of chyle leak. Patients in the DA group, the mean times to first flatus, liquid diet, and soft diet were 1.4 ± 1.3 days, 1.5 ± 1.4 days, 4.0 ± 2.1 days, and there were no deaths within 30 postoperative days and no tumor recurrence within 12 months of follow-up. Compare with the CME group, patients in the DA group presented with the less blood loss (20.3 ± 10.4 ml vs 34.6 ± 22.2 ml, p < 0.001), the shorter hospital day (6.4 ± 2.2 days vs 7.5 ± 2.2 days, p = 0.007), and the higher lymph node lymph node harvested (48.3 ± 12.7 vs 33.0 ± 11.2, p < 0.001). The age, BMI, sex, tumor location, operative time, pathology stage, and the rate postoperative complication between the two groups were no significantly different, which were summarized in Table 1. As shown in the survival curves (Fig. 2), the postoperative survival in the two groups was no significantly different (p = 0.74).
| Variable | DA group(n = 65) n (%) or Mean ± SD | Control group (n = 65) n (%) or Mean ± SD | p |
|---|---|---|---|
| Age (years) | 55.0 ± 12.1 | 53.2 ± 4.0 | 0.272 |
| Sex | 1 | ||
| Male | 38 (58.5) | 35 (53.8) | |
| Female | 27 (41.5) | 30 (46.2) | |
| BMI (kg/m2) | 22.4 ± 3.1 | 22.6 ± 3.2 | 0.748 |
| Location | 0.371 | ||
| Caecum | 18 (27.7) | 12 (18.5) | |
| Ascending colon | 20 (30.8) | 29 (44.6) | |
| Hepatic flexure | 24 (36.9) | 22 (33.8) | |
| Transverse colon (right third) | 3 (4.6) | 2 (3.1) | |
| Operative time (min) | 145.1 ± 32.5 | 140.9 ± 34.9 | 0.484 |
| Blood loss (ml) | 20.3 ± 10.4 | 34.6 ± 22.2 | < 0.001 |
| Postoperative hospital stay (d) | 6.4 ± 2.2 | 7.5 ± 2.2 | 0.007 |
| Lymph node harvested | 48.3 ± 12.7 | 33.0 ± 11.2 | < 0.001 |
| Pathology TNM stage† | 0.748 | ||
| I | 6 (9.2) | 6 (9.2) | |
| II | 35 (53.8) | 39 (60.0) | |
| III | 24 (36.9) | 20 (30.8) | |
| Postoperative complication | |||
| Total | 3 (4.6) | 5 (7.7) | 0.465 |
| Wound infection | 1 | 1 | |
| Chyle leak | 1 | 1 | |
| Diarrhoea | 0 | 1 | |
| Abscess | 1 | 1 | |
| Pneumonia | 0 | 1 | |
| SD, standard deviation. | |||
| † TNM stage according to the American Joint Committee on Cancer, 7th ed | |||
CME was first introduced as the standard surgical procedure for colon cancer by professor Hohenberger in 2009 [3]. It was emphasized that the sharp dissection should be performed along the mesocolon fascial plane, which reduces the local recurrence rate.
The surgical technique introduced in the present study is based on the concept of developmental anatomy and has several differences as follows: (1) Not only is the right-side mesocolon intact, but also the mesogastrium, the transverse mesocolon, the prehypogastric nerve fascia, the mesoduodenum, the mesopancreas, mesointestin, and left-side mesocolon was fully preserved after en-block resection; (2) This surgical technique has a clear border of right hemicolectomy (Cephalic side: the transverse mesocolon. Dorsal side: the prehypogastric nerve fascia, the mesoduodenum, and the mesopancreas. Medial side: left mesocolon. Lateral side: parietal pelvic fascia); (3) CME requires a central vascular ligation (CVL) of the trunk vessels, which might lead to bleeding and loss of surgical anatomy during the CVL procedure [5, 6]. The excessive dissection of the CVL may damage the integrity of the resected mesocolon. In addition, root ligation of CVL and vascular sheath skeletonization may cause unnecessary damage to the vascular sheath, small nerve branches, and surrounding tissue. In the present study, all intra-mesenteric vessels were ligated within the fused fascial space regardless of their name; therefore, the mesocolon and vascular sheath were fully preserved, thus reducing the risk of postoperative diarrhea, celiac disease, superior mesenteric vein injury, as well as lymphatic leakage.
Laparoscopic complete mesocolic excision based on the concept of developmental anatomy is technically safe and feasible for right-sided colon cancer.
Funding Declaration
The authors declare that this study was not funded by any government agency or commercial sponsor
Author Contribution
Kai Li, Fengyu Cao and Yongbin Zheng participated in study conception, drafting of manuscript, and critical revision of manuscript. Kai Li made the statistical analysis and participated in the acquisition and interpretation of data. Fengyu Cao, Xiaobo He, and Yongbin Zheng performed the surgery. All authors reviewed the manuscript.
Ethics Declarations
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments
Informed consent Appropriate consent has been taken from the patient for use of surgical information in the video, and the written consent was provided by all patients. The identity of the patient has not been revealed.
Conflict of interest The authors declare no conflict of interest.