Robotic Complete Mesocolic Excision Versus Conventional Laparoscopic Hemicolectomy for Right-Sided Colon Cancer

Abstract

Background:

Robotic technique has been proposed to overcome the limitations of laparoscopic surgery. In this study, we aimed at determining whether robotic complete mesocolic excision (CME) for right-sided colon cancer can be safe and effective as conventional laparoscopic right hemicolectomy (CLRH).

Materials and Methods:

Between February 2015 and September 2017, patients undergoing robotic right CME and CLRH with curative intent for right-sided colon cancer were included. Patient characteristics, short-term and histopathological outcomes were compared between the groups.

Results:

Ninety-six patients (robotic, n = 35) were included in this study. The operative time (286 ± 77 versus 132 ± 40 minutes, P = .0001) was significantly longer in the robotic group. There were no conversions in either group. No significant differences existed between the groups regarding the mean estimated blood loss, time to first flatus, length of hospital stay (6 ± 3 versus 6 ± 3 days, P = .64), and follow-up times (robotic 15 ± 8 versus laparoscopic 16 ± 10 months P = .11). Overall complication rates (n = 10 [29%] versus n = 15 [25%], P = .67) were similar. In the robotic group, vascular injury occurred in 2 patients, and both were repaired robotically. The mean number of harvested lymph nodes was significantly higher (41 ± 12 versus 33 ± 10, P = .04) and length between the vascular tie and colonic wall was longer (13 ± 3.5 versus 11 ± 3, P = .02) in the robotic group.

Conclusion:

Although robotic right CME seems equally safe to CLRH in terms of short-term morbidity, future prospective randomized trials are needed to define its role for treatment of right colectomy.

Introduction

Surgical treatment for colorectal cancer has evolved with the introduction of new surgical equipment and techniques.^1,2 Total mesorectal excision is currently accepted as the standard treatment for rectal cancer. It has become a model for colon cancer surgery as in the complete mesocolic excision (CME) technique.^1,2 Lack of standardization in the surgical treatment of colon cancer results in suboptimal surgical treatment in a considerable portion of colectomies.³ Although long-term results are unclear,⁴ some evidence support the superiority of CME compared with non-CME for colon cancer in terms of local recurrence-free survival.⁵ CME has been shown to provide promising oncological outcomes based on the studies evaluating resected specimen and large retrospective series, mainly including open operations.²

The CME technique includes central vascular ligation of both the arteries and the veins supplying the tumor-bearing colonic segment within an intact mesocolon.² Although the feasibility of laparoscopic CME for right-sided colon cancer has been demonstrated,² this approach has not been widely preferred due to technical limitations of the standard laparoscopic equipment. Rigid instrumentation, lack of depth perception, and limited range of motion are the major limitations of the laparoscopic technique for performing safer dissections that are especially close to the superior mesenteric vein (SMV) during CME.^6–9 Robotic techniques have been proposed to overcome the limitations of laparoscopic surgery. In this study, we aimed at determining whether robotic complete mesocolic excision (RCME) can be performed with an equal short-term morbidity as conventional laparoscopic right hemicolectomy (CLRH) which is the mainstay treatment for right-sided colon cancer.

Materials and Methods

Between February 2015 and September 2017, patients who underwent RCME or CLRH for right-sided colon cancer with curative intent at two tertiary care referral centers by two surgical teams were included. Exclusion criteria were: undergoing open surgery, having a benign disease, familial colorectal cancer, or multiple distant metastasis, thus making the curative approach impossible. Patient characteristics, perioperative outcomes, short-term (30 day) complications, and histopathologic results were compared between the RCME and CLRH groups. The study protocol was approved by the Institutional Review Board.

Patient characteristics were gender, age, American Society of Anesthesiology (ASA) score, body mass index, history of prior abdominal surgery, and tumor location. Perioperative outcomes were operative time, estimated blood loss, conversion to open or laparoscopic surgery (for the RCME group), time to first flatus, length of stay, and short-term complications (within 30 days). The histopathologic results, including distal resection margin, tumor size, radial margin, number of harvested lymph nodes, length between the vascular tie and the colon wall, and pathological tumor, node, metastasis (TNM) stage, were recorded. The American Joint Committee on Cancer's (AJCC) cancer staging manual was used for staging of the tumors.¹⁰ Circumferential radial margin involvement was accepted positive for tumors ≤1 mm close to the surgical margin.

Definitions

Anastomotic leak was defined as a break in the integrity of the anastomosis documented by a combination of clinical, endoscopic, radiologic, and operative findings.¹⁰ Bowel obstruction/ileus was defined as the presence of at least three of the following five symptoms: nausea, abdominal pain, vomiting, abdominal distension, and absence of flatus and/or stool within the past 24 hours, findings indicating obstruction on plain radiographic or contrast studies, or a diagnosis of intestinal obstruction as confirmed by surgery.¹¹ For RCME, conversion was defined as the completion of any part of the procedure with an open or conventional laparoscopic technique, excluding the delivery of the specimen. For CLRH, conversion was defined as completion of any part of the procedure with an open technique, excluding the extracorporeal anastomosis and the delivery of the specimen.¹² Overall operative time was defined as the time from the first skin incision to final closure of the abdominal wall. Discharge criteria were similar in both groups and included tolerance of meals without nausea or vomiting, established bowel or stoma function, adequate pain control with oral analgesia, and independent ambulation.¹³ Readmission was defined as the need for inpatient treatment, without scheduled admission, for any medical reason within the first 30 days after discharge from the index hospital stay.¹⁴

Operative techniques

Robotic complete mesocolic excision

All of the RCME operations were carried out with the da Vinci Xi^® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA). Detailed information regarding our operative technique was previously described.^15,16

Conventional laparoscopic right hemicolectomy

The patient was positioned in a modified lithotomy with the legs slightly separated from each other with the help of stirrups. Surgeon and camera assistant stood at the left side of the patient. Four trocars (two 5-mm, one 10-mm, and one 12-mm) were used. The medial to lateral (vascular approach) technique was used in all laparoscopic operations. The ileocolic vessels were clipped close to the SMV with the help of endo clips and divided. The right colic vessels were clipped with endoclips and divided by using endo shears. Then, dissection of the colonic mesentery was carried out in a cephalad direction and the middle colic vessels were identified. In patients with cecal or ascending colon tumors, the right branches of the middle colic vessels were dissected and divided. In patients with tumors located in the hepatic flexure and proximal transverse colon, middle colic vessels were clipped and divided before they gave out branches. Proximal and distal transections of the bowel were performed intracorporeally, whereas anastomosis was made either intra- or extracorporeally based on the surgeon's preference.

Statistical analysis

Continuous variables were described as mean ± standard deviation unless stated otherwise. Categorical variables were described as n (%). Continuous variables were compared with Wilcoxon rank sum test for quantitative data, and categorical variables were compared by using the chi-square test. A P value of <0.05 was considered significant.

Results

Ninety-six patients were included (Table 1). The operative time (286 ± 77 versus 132 ± 40 minutes; P = .0001) was significantly longer in the RCME group. There were no conversions to open surgery in either group. The overall complications and postoperative morbidity were comparable between the groups (Table 2). A SMV injury occurred while dissecting the aberrant small branches and was repaired robotically in 2 patients with prolene sutures in the RCME group.

Table 1.

Patient Characteristics and Operative Outcomes

	RCME (n = 35)	CLRH (n = 61)	P-value
Gender, F, n (%)	15 (42)	30 (50)	.55
Age, years, mean ± SD	65 ± 13	65 ± 13	.89
ASA score, median (range)	2 (1–4)	2 (1–4)	.78
BMI, kg/m²	29 ± 5	27 ± 5	.75
Prior abdominal surgery, n (%)	8 (23)	21 (35)	.39
Cecum and ascending colon tumor, n (%)	24 (69)	42 (69)	.98
Hepatic flexure and proximal transverse colon tumor, n (%)	11 (31)	19 (31)	.98
Blood loss, mL, mean ± SD	75 ± 70	73 ± 57	.57
Conversion to open, n (%)	0	0	—
Stoma, n (%)	0	1 (2)	.36
Flatus, days, mean ± SD	3 ± 1	2 ± 1	.16
LOS, days, mean ± SD	6 ± 3	6 ± 3	.64
Follow up time, months, mean ± SD	15 ± 8	16 ± 10	.11

ASA, American Society of Anesthesiologists; BMI, body mass index; CLRH, conventional laparoscopic right hemicolectomy; F, female; LOS, length of stay; RCME, robotic complete mesocolic excision; SD, standard deviation.

Table 2.

Postoperative Outcomes

	RCME (n = 35), n (%)	CLRH (n = 61), n (%)	P-value
Postoperative overall complications	10 (29)	15 (25)	.67
Ileus	2 (5)	8 (13)	.32
Anastomotic leak	0	3 (5)	.30
Pulmonary embolism	1 (3)	0	.37
Atelectasis	2 (5)	0	.13
Intraabdominal abscess formation	0	1 (1)	1
Bleeding requiring reoperation	1 (3)	1 (1)	1
Wound infection	4 (11)	1 (1)	.06
Wound dehiscence	1 (3)	0	.37
Cerebrovascular event	0	1 (1)	1
Sepsis	0	1 (1)	1
Postoperative Clavien Dindo³³ I–II complications	9 (26)	11 (18)	.37
Postoperative Clavien Dindo³³ III–IV complications	1 (3)	4 (7)	.65
Intraoperative complications	2 (5)	0	.13
Reoperation within 30 days	1 (3)	3 (5)	1
Readmission	2 (5)	0	.13

CLRH, conventional laparoscopic right hemicolectomy; RCME, robotic complete mesocolic excision.

The TNM stages were similar between the two groups (Table 3). The distal and proximal resection margins, tumor sizes, and radial margin involvements were also comparable between the groups. There were no positive surgical margins in either group. RCME provided significantly higher number of lymph nodes after right (P = .048) and extended right (P = .0001) colectomies compared to CLRH. The length between vascular tie and colon wall was also longer in the RCME group (P = .02).

Table 3.

Histopathological Results

	RCME (n = 35)	CLRH (n = 61)	P-value
Proximal resection margin, cm, mean ± SD	13.1 ± 9.3	14.8 ± 9.3	.4
Distal resection margin, cm, mean ± SD	16 ± 7	13 ± 8	.9
Tumor size, cm, mean ± SD	5 ± 2	5 ± 3	.6
Radial margin involvement ≤1 mm, n (%)	1 (3)	5 (8)	.41
Positive surgical margins, n (%)	0	0
Overall LN harvested, mean ± SD	41 ± 12	33 ± 10	.04
Extended right colectomy, n (%)	15 (43)	19 (31)	.25
LN harvested, mean ± SD	47 ± 10	35 ± 12	.0001
Right colectomy, n (%)	20 (47)	42 (69)	.25
LN harvested, mean ± SD	36.6 ± 10.8	32.6 ± 8.5	.048
Length between vascular tie and colon wall, cm, mean ± SD	13 ± 3.5	11 ± 3	.02
pTNM stage, n (%)			.66
0	2 (6)	3 (5)
I^*	5 (14)	7 (11)
II	13 (37)	20 (32)
III	12 (34)	29 (48)
IV	3 (9)	2 (3)

Tumor deposits were seen in a patient in the RCME and 4 patients in the CLRH groups.

Bold values indicate significance.

CLRH, conventional laparoscopic right hemicolectomy; LN, lymph nodes; pTNM, pathologic tumor, node, metastasis; RCME, robotic complete mesocolic excision; SD, standard deviation.

Discussion

Despite obtaining superior pathological specimens with an increased number of lymph nodes and longer vascular pedicles compared with conventional resections, serious complications may occur during extensive dissections for achieving CME.¹⁷ Technical difficulties, potential intraoperative and postoperative complications are the major factors preventing surgeons from performing minimally invasive CME in their routine practice. The results of this study reveal that RCME can be performed with an equal short-term morbidity as CLRH for right-sided colon cancer.

The methodology of the study was designed to compare two different operative modalities and techniques: robot versus laparoscopy use for CME and non-CME resections, respectively, in patients with right colon cancer. We believe that this comparison would be much better to assess the logic behind using the robotic technique in clinical practice, which has been evolving to reduce the limitations of laparoscopy. Although comparing robotic versus laparoscopic right CME seems more appropriate from a methodological standpoint, this comparison would not give us the chance to compare the proposed technical and short-term morbidity benefits of using the robotic technique for a more complex procedure over the mainstay minimally invasive treatment, which is CLRH. Although it is doable,⁷ the laparoscopic technique can be deficient in handling some complex steps and intraoperative complications of right CME. In our series, there were two instances of SMV injury in the RCME group. Both of these injuries occurred during the dissection of the aberrant small branches connected to the SMV and were repaired robotically without further complications. Robotic surgery has been developed to overcome the limitations of laparoscopy with its wristed instruments, high-quality suturing capacity, and stable camera with 3D view.⁹ We believe that the visual and ergonomic advantages of the robotic system help us overcome the technical complexity and intraoperative complications of minimally invasive right CME without additionally complicating the perioperative course. Although both of our surgical teams have more than 15 years of laparoscopic experience and our robotic team has 7 years of robotic colorectal surgery experience, the procedures in which the SMV injuries were repaired robotically would be converted to open surgery urgently if we had aimed for a laparoscopic CME. Although pre-emptive conversions may provide similar outcomes with open surgery, reactive conversions that are due to an intraoperative complication are associated with increased postoperative morbidity.¹⁸ Abundant blood loss and further inadvertent organ injuries can occur during an emergent laparotomy to control a major vascular injury that occurred during a laparoscopic procedure.

Although there are large patient series reporting the safety of laparoscopy for right CME^19–21 without major complications, the relatively low harvested lymph nodes (19, 21, 27) in the reports have us questioning radicality and quality of those laparoscopic CME operations. Less radical operations would directly result in less operative morbidity. The original report by Hohenberger et al. reported 32 median number of lymph nodes with 20% and 3% in hospital morbidity and mortality, revealing the potential complexity of the CME procedure. The numbers of harvested lymph nodes were strikingly high in both of our study groups; even the number of lymph nodes of our CLRH group was higher than those reported in the laparoscopic CME series^22–25 The importance of the nodal yield lies in the fact that it is a proven marker for surgical quality and one of the most important factors for staging the disease.²⁶ Even in node negative disease, high lymph node yield in histopathological examination is reported to correlate with better prognosis.²⁷ Further, Hohenberger et al. demonstrated a significant increase in overall survival when the number of removed lymph nodes was higher than 28.² RCME provided higher lymph node yields in both regular and extended right hemicolectomy procedures, regardless of the tumor location compared with a very good quality of CLRH performed by experienced surgeons in our study.

The presence of tumor deposits in the resected specimen is an important indicator of advanced disease.³ The deposits may be located at any place between the primary tumor and the vascular roots of the specimen.^27,28 Central vascular ligation and dissection between the embryologic planes can provide wider and an intact resection material, facilitating the removal of any present tumor deposits along with the resected specimen. This technical characteristic of the CME technique provides an absolute oncologic superiority compared with other conventional techniques, in which the main vessels are transected at a distant point from their origins. In this study, tumor deposits were seen in overall 5 patients. When compared between the groups, the mean length between the vascular tie and the colon wall was significantly longer in the RCME specimens. Tumor deposits located in proximity to the vascular roots can be easily missed in non-CME resections. Although the impact of tumor deposits on survival is still inconclusive, early studies recommend considering the presence of tumor deposits as at least equally important to node-positive disease in predicting patient outcome.²⁹

Limitations of this study are lack of long-term data and a relatively small patient population. Increased cost is still the major drawback of the robotic technique preventing its widespread use expectedly. Our robotic surgeons prefer to use robots for right CME to achieve good quality of resected specimen and a safer perioperative course, whereas our surgeons performing CLRH are well aware of the differences in the resected specimens between the two operative techniques. However, they currently prefer to continue with the conventional resection technique due to unproven short- and long-term oncologic benefits of CME and its potential short- and long-term complications.

So far, the trials evaluating the value of robotic colorectal surgery, including the ROLARR trial, have major structural drawbacks, including the inclusion of a wide diversity of surgeons and techniques in terms of experience and heterogeneity of operative techniques decrease the reliability of this trials.³⁰ To our knowledge, there are two ongoing prospective randomized trials evaluating the efficacy of D3 versus D2 lymph node dissection in colon cancer (the COLD and RELARC trials).^31,32 Although robotic right CME seems equally safe to CLRH in terms of short-term morbidity, future prospective randomized trials are needed to define its role for treatment of right colectomy.

Footnotes

Acknowledgment

The authors thank Dr. Eren Esen for his help for data managing and statistics.

Authors' Contributions

Study conception design: E.A., T.K., V.O., B.B., E.B., I.H., D.B., T.K.Y., O.B., B.G.; data acquisition: E.A., V.O., T.K.Y., O.B., B.G., T.K., B.B., E.B., I.H., D.B.; data analysis and interpretation: E.A., T.K., V.O., T.K.Y., B.B., E.B., I.H., D.B., O.B., B.G.; drafting the article: T.K.Y., E.A., V.O., T.K.; critical revision for intellectual content: E.A., T.K., V.O., B.B., E.B., I.H., D.B., T.K.Y., O.B., B.G.; final approval of the article: D.B., T.K., I.H., B.B., E.B., V.O., E.A., O.B., B.G., T.K.Y.; agree to be accountable for all aspects of work: T.K.Y., E.A., V.O., O.B., B.G., B.B., E.B., I.H., T.K., D.B.

Disclosure Statement

No competing financial interests exist.

References

Heald

, Ryall

. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet, 1986; 1:1479–1482.

Hohenberger

, Weber

, Matzel

, Papadopoulos

, Merkel

. Standardized surgery for colonic cancer: Complete mesocolic excision and central ligation–technical notes and outcome. Colorectal Dis, 2009; 11:354–364.

Wells

, Hawkins

, Krishnamurthy

, et al. Omission of adjuvant chemotherapy is associated with increased mortality in patients with T3N0 colon cancer with inadequate lymph node harvest. Dis Colon Rectum, 2017; 60:15–21.

Gouvas

, Agalianos

, Papaparaskeva

, Perrakis

, Hohenberger

, Xynos

. Surgery along the embryological planes for colon cancer: A systematic review of complete mesocolic excision. Int J Colorectal Dis, 2016; 31:1577–1594.

Gao

, Wang

, Cui

, et al. Efficacy and safety of complete mesocolic excision in patients with colon cancer: Three-year results from a prospective, nonrandomized, double-blind, controlled trial. Ann Surg, 2018.[Epub ahead of print]; DOI: 10.1097/SLA.0000000000003012.

Jamali

, Soweid

, Dimassi

, Bailey

, Leroy

, Marescaux

. Evaluating the degree of difficulty of laparoscopic colorectal surgery. Arch Surg, 2008; 143:762–767 ; discussion 768.

Formisano

, Misitano

, Giuliani

, Calamati

, Salvischiani

, Bianchi

. Laparoscopic versus robotic right colectomy: Technique and outcomes. Updates Surg, 2016; 68:63–69.

Ogino

, Takemasa

, Horitsugi

, et al. Preoperative evaluation of venous anatomy in laparoscopic complete mesocolic excision for right colon cancer. Ann Surg Oncol, 2014; 21,(Suppl 3):S429–S435.

Acar

, Comert

, Avsar

, Celik

, Kuzu

. Dynamic article: Surgical anatomical planes for complete mesocolic excision and applied vascular anatomy of the right colon. Dis Colon Rectum, 2014; 57:1169–1175.

10.

Egner

. AJCC cancer staging manual. JAMA, 2010; 304:1726–1727.

11.

Fazio

, Kiran

, Remzi

, et al. Ileal pouch anal anastomosis: Analysis of outcome and quality of life in 3707 patients. Ann Surg, 2013; 257:679–685.

12.

El-Gazzaz

, Kiran

, Remzi

, Hull

, Geisler

. Outcomes for case-matched laparoscopically assisted versus open restorative proctocolectomy. Br J Surg, 2009; 96:522–526.

13.

Delaney

, Fazio

, Senagore

, Robinson

, Halverson

, Remzi

. ‘Fast track’ postoperative management protocol for patients with high co-morbidity undergoing complex abdominal and pelvic colorectal surgery. Br J Surg, 2001; 88:1533–1538.

14.

Turina

, Pennington

, Kimberling

, Stromberg

, Petras

, Galandiuk

. Chronic pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Effect on quality of life. J Gastrointest Surg, 2006; 10:600–606.

15.

Bilgin

, Aytac

, Erenler

, et al. Robotic mesocolic excision with a ‘top to down no-touch’ technique for right colon cancer—A video vignette. Colorectal Dis, 2017; 19:866–867.

16.

Ozben

, Baca

, Atasoy

, et al. Robotic complete mesocolic excision for right-sided colon cancer. Surg Endosc, 2016; 30:4624–4625.

17.

Wang

, Gao

, Shen

, et al. Safety, quality and effect of complete mesocolic excision vs non-completemesocolic excision in patients with colon cancer: A systemic review and meta-analysis. Colorectal Dis, 2017; 19:962–972.

18.

Belizon

, Sardinha

, Sher

. Converted laparoscopic colectomy: What arethe consequences?. Surg Endosc, 2006; 20:947–951.

19.

Matsuda

, Iwasaki

, Sumi

, et al. Laparoscopic complete mesocolic excision for right-sided colon cancer using a cranial approach: Anatomical and embryological consideration. Int J Colorectal Dis, 2017; 32:139–141.

20.

Siani

, Lucchi

, Berti

, Garulli

. Laparoscopic complete mesocolic excision with central vascular ligation in 600 right total mesocolectomies: Safety, prognostic factors and oncologic outcome. Am J Surg, 2017; 214:222–227.

21.

, Zhang

, Liu

, et al. A novel and safe approach: Middle cranial approach for laparoscopic right hemicolon cancer surgery with complete mesocolic excision. Surg Endosc, 2018; 32:2567–2574.

22.

Siani

, Pulica

. Laparoscopic complete mesocolic excision with central vascular ligation in right colon cancer: Long-term oncologic outcome between mesocolic and non-mesocolic planes of surgery. Scand J Surg, 2015; 104:219–226.

23.

Huang

, Wei

, Fang

, et al. Comparison of laparoscopic versus open complete mesocolic excision for right colon cancer. Int J Surg, 2015; 23,(Pt A):12–17.

24.

Bae

, Saklani

, Lim

, et al. Laparoscopic-assisted versus open complete mesocolic excision and central vascular ligation for right-sided colon cancer. Ann Surg Oncol, 2014; 21:2288–2294.

25.

, Baik

, Oh

, et al. Oncological outcomes of complete versus conventional mesocolic excision in laparoscopic right hemicolectomy. ANZ J Surg, 2018; 88:E698–E702.

26.

Chang

, Rodriguez-Bigas

, Skibber

, Moyer

. Lymph node evaluation and survival after curative resection of colon cancer: Systematic review. J Natl Cancer Inst, 2007; 99: 433–441.

27.

Kessler

, Hohenberger

. Extended lymphadenectomy in colon cancer is crucial. World J Surg, 2013; 37:1789–1798.

28.

Sondenaa

, Quirke

, Hohenberger

, et al. The rationale behind complete mesocolic excision (CME) and a central vascular ligation for colon cancer in open and laparoscopic surgery: Proceedings of a consensus conference. Int J Colorectal Dis, 2014; 29:419–428.

29.

Jin

, Roth

, Rock

, Washington

, Lehman

, Frankel

. The impact of tumor deposits on colonic adenocarcinoma AJCC TNM staging and outcome. Am J Surg Pathol, 2015; 39:109–115.

30.

Jayne

, Pigazzi

, Marshall

, et al. Effect of robotic-assisted vs conventional laparoscopic surgery on risk of conversion to open laparotomy among patients undergoing resection for rectal cancer: The ROLARR randomized clinical trial. JAMA, 2017; 318:1569–1580.

31.

Study of Oncological Outcomes of D3 Lymph Node Dissection in Colon Cancer (COLD). (NLM Identifier: NCT03009227). https://clinicaltrials.gov/ct2/show/NCT03009227 (accessed December 4, 2017).

32.

, Xu

, Xue

, et al. The radical extent of lymphadenectomy—D2 dissection versus complete mesocolic excision of laparoscopic right colectomy for right-sided colon cancer (RELARC) trial: Study protocol for a randomized controlled trial. Trials, 2016; 17:582.

33.

Dindo

, Demartines

, Clavien

P-A

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240:205–213.