Abstract
Aim: To clarify the benefits of robotic-assisted laparoscopic surgery (RALS) regarding short-term outcomes in patients with technically demanding rectal cancer (TDRC). Patients and Methods: Between April 2015 and September 2019, 88 TDRC cases were identified from our database, and divided into the RALS (n=32) and conventional laparoscopic surgery (CLS) (n=56) groups. TDRC was defined as mid-rectal tumors presenting at least one of the following risk factors: Male sex, high body mass index, T4 stage, bulky tumor, or low rectal tumor. Results: Patient baseline characteristics were similar in both groups. One and 15 patients developed anastomotic leakage in the RALS and CLS groups (3% vs. 27%, p<0.01), respectively. The postoperative complication rate was lower in the RALS group (19% vs. 43%, p=0.03). Multivariate analysis showed the surgical approach to be an independent predictor for anastomotic leakage. Conclusion: RALS has potential advantages to prevent anastomotic leakage complications in patients with TDRC.
In rectal cancer, the quality of the surgical procedure defines the technical outcomes, such as anastomotic leakage (AL) (1), urogenital dysfunction (2), and circumferential resection margin (3).
Robotic-assisted laparoscopic surgery (RALS) for rectal cancer has gained popularity due to its advanced technology allowing free-moving multi-joint forceps, high-quality three-dimensional imaging, and a motion-scaling function, potentially improving operative accuracy in narrow surgical fields. Recent studies comparing conventional laparoscopic (CLS) and open surgery for rectal cancer have failed to indicate superiority regarding the technical outcomes of CLS (4, 5). One possible explanation involves the technical difficulty of working with the linear rigid laparoscopic instrument deep in the pelvis (5).
A previous randomized controlled trial comparing RALS and CLS, in which patients with upper, mid, and low rectal cancer were included, showed equivalent short-term outcomes between the two examined methods; however, one sub-analysis showed the superiority of RALS relative to conversion rates in male patients (6). This suggested that RALS may be beneficial for selective patients, especially for those with technically demanding rectal cancer (TDRC); nevertheless, specific characteristics identifying patients who may benefit from the procedure and its advantages remain to be clarified.
The aim of this study was to examine whether RALS had beneficial effects on short-term outcomes, especially in patients with TDRC.
Patients and Methods
Definition of technically demanding rectal cancer. Previous studies have identified factors correlated with technical difficulty in rectal cancer surgery including low rectal tumor, male sex, high body mass index (BMI), and large tumor size (7-9). TDRC was defined as mid-rectal tumors (5-10 cm from the anal verge) presenting at least one of the following risk factors: male sex, high BMI (>25 kg/m2), T4 stage, bulky tumor (>5 cm), or low rectal tumor (<5 cm of the anal verge).
Study design. This retrospective study extracted information from a prospectively colorectal database including data on patient, operative, and pathological characteristics, preoperative assessments, postoperative complications, and follow-up. Between April 2015 and September 2019, a total of 169 patients underwent laparoscopic resection for rectal cancer at the Yokohama City University Hospital and at three community teaching hospitals located in Yokohama City. Forty-eight patients did not meet the TDRC criteria, 18 underwent extended surgical procedures (i.e., concomitant gastrectomy or lateral lymph node dissection), and 15 out of these 169 patients with non-sphincter saving surgery were excluded from the study. Ultimately, 88 patients with TDRC were divided into the RALS (n=32) and the CLS group (n=56) according to the type of the surgery they had undergone (Figure 1). All study protocols were approved by the Yokohama City University Institutional Review Board (approval no.: 170700003). This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was waived owing to the retrospective nature of the study. Instead of obtaining written informed consent, the details of the study protocol were provided to patients via a notice board in the hospitals and were published on the hospital websites.
Indications for RALS and CLS. RALS was adopted only at the University Hospital and was implemented as the first-choice treatment for rectal cancer from June 2017. Previously, rectal cancer surgery had been performed by CLS. In the three community teaching hospitals, laparoscopic surgery was the first choice considering tumor factors and patient characteristics.
Indications for diverting ileostomy. The general indications for diverting ileostomy differed for RALS and CLS procedures. For CLS, low rectal cancer or cases in which the surgeon anticipated AL based on the patient's history or intraoperative findings were indications for diverting ileostomy. For RALS at the University Hospital, the indication for diverting ileostomy depended on the phase. For the first 20 cases (initial phase), the indication was low or mid-rectal tumors in male patients, or cases in which the surgeon anticipated potential AL. After experiencing 20 patients (experienced phase), the procedure's indications were the same as those for CLS, as mentioned above.
Operative procedure. We established a standardized seven-step total mesorectal excision approach regarding RALS procedure. The robotic system used was the Da Vinci Si surgical system (Intuitive, Sunnyvale, CA, USA). We previously described the details of our operating technique (10). In CLS, initial access to the abdomen was usually achieved via the umbilical port. Once pneumoperitoneum was established, four additional ports were positioned. Vessel ligation with lymph node dissection was performed, followed by left-sided colon mobilization. Following rectal mobilization and transection, we extracted the pathological specimen via a 4- to 6-cm umbilical incision. For both RALS and CLS, reconstruction was performed by a double-stapling technique using a circular stapler.
Postoperative complications. Postoperative complications were evaluated using the Clavien–Dindo (CD) classification system (11). Grade 2 to 5 postoperative complications that occurred during hospitalization or within 30 days after surgery were prospectively recorded. Grade 1 complications were not evaluated in order to exclude the possibility of description bias.
Outcomes of interest. The primary and secondary outcomes of interest were AL and postoperative complication rates, respectively. Statistical analysis. The significance of the associations between the study groups and clinicopathological parameters was assessed using Fisher's exact or the t-test. Relapse-free survival curves were constructed using the Kaplan–Meier method performing group comparisons using the log-rank test. All statistical analyses were conducted using the EZR (Jichi Medical University, Saitama, Japan) and R (version 3.4.3) (The R foundation for statistical computing, Vienna, Austria) software (12). All p-values were two-sided, and statistical significance was set at p<0.05.
Results
Patient characteristics. The baseline characteristics of patients of both the RALS and the CLS groups are presented in Table I. There were no significant differences between the two groups regarding age, sex, BMI, American Society of Anesthesiologists classification, tumor location, TNM status, histological type, and tumor diameter.
Short-term outcomes. Table II summarizes the short-term outcomes of the patients. The operative time was longer in the RALS than in the CLS group (338 vs. 249 min, p<0.01). The amount of blood loss was similar for the two groups (10 vs. 10 g, p=0.19). No conversion was observed in the RALS group (0% vs. 7%, p=0.29). Diverting ileostomy was performed more often in the RALS than in the CLS group (81% vs. 44%, p<0.01).
The incidence rate of postoperative complications (CD grade 2 or more) was better for the RALS than the CLS group (19% vs. 43%, p=0.03). Regarding AL (CD grade 2 or more), the RALS group had better outcomes than the CLS group (3% vs. 27%, p<0.01). In the RALS group, ileus was the most frequent complication. Most cases of ileus involved outlet obstruction of the diverting ileostomy. In the CLS group, AL was the most frequent problem. The postoperative hospital stay was shorter in the RALS group (14 vs. 16 days, p<0.01). Negative radial margins were achieved in all patients.
Risk factors for AL. As the incidence of AL of CD grade 2 or more was the most frequent event, univariate and multivariate logistic regression analyses of risk factors for AL were performed. Tumor location (lower rectum vs. mid-rectum), approach (CLS vs. RALS), and diverting ileostomy (no vs. yes) were evaluated as risk factors by univariate analysis. Of these, the surgical approach remained an independent predictor of AL, with CLS being associated with a more than 10-fold risk of AL (Table III).
Discussion
Here, we demonstrated that RALS was beneficial in terms of AL in patients with TDRC. In Japan, the National Health Insurance System began to cover the RALS procedure for rectal cancer in April 2018 and since then, this procedure has become widespread. The rationale for RALS was to overcome restricted control of the operating device deep in the pelvis and to improve patient outcomes.
Patient flow diagram. CLS: Conventional laparoscopic surgery; RALS: robotic-assisted laparoscopic surgery; BMI: body mass index.
Patient characteristics (n=88).
Short-term outcomes (n=88).
Univariate and multivariate analysis for anastomotic leakage.
Previous reports on robot-assisted laparoscopic surgery (RALS) and anastomotic leakage (AL).
In rectal cancer surgery, AL, urogenital dysfunction, and circumferential resection margin are indicators of technical quality (1-3) and may be defined as ‘technical outcomes’. Regarding the urogenital dysfunction, few studies have demonstrated better urogenital function in RALS than in CLS (13, 14); however, most studies have shown equivalent results (6, 15-17). The circumferential resection margin status after RALS and CLS was also similar (6, 14-19).
Previous reports comparing the differences in AL outcomes after RALS and CLS are shown in Table IV. The range of AL incidence in RALS and CLS ranged from 1.5-12.2% and 3.6-11.6%, respectively (6, 13-16, 18, 19). It is difficult to effectively compare these studies due to differences in the eligibility criteria: Four studies included upper rectal cancer cases (6, 16, 18, 19), while another three studies did not (13-15). No previous reports have specifically focused on TDRC as in the present study. The evaluated AL grade also varied among the reported studies: AL was evaluated at grades 3-4 or 1-4 in two and one studies, respectively. Four studies did not report the grade. The CLS series in the present study had a relatively higher rate of AL (9% with CD of grade 3 or more) than two previous studies (16, 18) (3.6% and 7.3% with CD of grade 3 or more). This disparity may be attributed to differences in the eligibility criteria in the reported series, which included the upper rectum, while our series included only cases of TDRC.
Our study found that the surgical approach was the only independent predictor of AL incidence and is the first to demonstrate that RALS significantly reduced the risk of AL. The risk factors of AL have been extensively reported in previous studies and include male sex, low rectal tumor, narrow pelvis, obesity, and bulky tumor (7, 9, 20, 21). The underlying mechanisms defining why these factors are risk factors have not been clearly established, however, they are all correlated with a narrow surgical field, which demands significant technical expertise in order to maintain an accurate dissecting line. In particular, rectal mobilization under poor visualization or an unstable surgical field may traumatize the rectal wall or its supplying vessels. Furthermore, insufficient rectal mobilization may be the cause of oblique rectal transection, which is a risk factor of AL (22). Thus, one interpretation of our results may be that advanced technologies in robotics may improve the quality of rectal mobilization and transection of the rectum, resulting in a reduced incidence of AL.
A major limitation of this study is that RALS was performed only at the University Hospital by a single surgeon, while CLS was performed at all hospitals by multiple surgeons. The differences between the two groups may have been affected by the diversity of the hospital facilities or the surgical procedure used. The second limitation lies in the differences in diverting ileostomy procedure used for the two groups. However, it is known that this procedure does not reduce AL itself but may limit its severity (9). Thus, in cases where the diverting ileostomy rate in the CLS group was higher, AL requiring radiological intervention or reoperation (CD of grade 3 or more) was lower. However, the frequency of AL itself (CD of grade 2 or more) was not changed.
Concluding, our findings suggest that RALS may contribute to improved anastomosis in patients with TDRC. Further investigation is warranted to provide further support for the advantages of RALS.
Acknowledgements
This work was supported, in part, by the nongovernmental organization Yokohama Surgical Research Group, Dr. Masumi Kamachi (Tokyo Shinagawa Hospital), Dr. Ryuji Tominaga (Fukuoka Wajiro Hospital), and Dr. Nobuko Yoshiki (Yoshiki Dermatology Clinic Ginza).
Footnotes
Authors' Contributions
Masakatsu Numata drafted the article. Masakatsu Numata, Keisuke Kazama, Atsushi Onodero, Kentaro Hara, Yosuke Atsumi, Hironao Okamoto, Toru Aoyama, Hiroshi Tamagawa, Teni Godai, Hiroyuki Saeki, Norio Yukawa, Manabu Shiozawa, Yasushi Rino, and Munetaka Masuda designed this study and analyzed the data. All Authors approved the final version of this manuscript.
Conflicts of Interest
The Authors declare no conflicts of interest in regard to this study.
- Received February 27, 2020.
- Revision received March 12, 2020.
- Accepted March 16, 2020.
- Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
