The comparison of health‐related quality of life and patient satisfaction between single‐incision and multiport laparoscopic colectomy for cancer: A sub‐study of a randomized, prospective clinical trial

Abstract Aim The present study clarified the effect on the health‐related quality of life and patient satisfaction of single‐incision laparoscopic colectomy compared with multiport laparoscopic colectomy for colorectal cancer. Methods We conducted a multicenter, randomized, control trial comparing single‐incision and multiport laparoscopic colectomy for colon cancer. We performed a pre‐planned secondary analysis of health‐related quality of life and patient satisfaction data of 200 patients. Health‐related quality of life was evaluated using the Japanese 36‐item Short Form Health Survey (SF‐36) version 2.0 before surgery and at 1 month after surgery. Patient satisfaction was compared using seven questionnaires at 1 month after surgery. Results One hundred patients were assigned to each group. After excluding 18 patients (9.0%) who did not complete the SF‐36, 182 patients (91.0%) were included in the analysis (92 cases of single‐incision laparoscopic colectomy and 90 cases of multiport laparoscopic colectomy). The SF‐36 scores at 1 month after surgery were not significantly different between the two arms. The role physical, bodily pain, vitality and physical component summary were significantly lower at 1 month after surgery than before in both groups. However, the role emotional was significantly lower after surgery than before only in the single‐incision laparoscopic colectomy group. In terms of patient satisfaction at 1 month after surgery, there were no significant differences in any of the seven items on the questionnaire. Conclusions Single‐incision laparoscopic colectomy was similar to multiport laparoscopic colectomy in terms of health‐related quality of life and patient satisfaction. However, single‐incision laparoscopic colectomy may be inferior than multiport laparoscopic colectomy in terms of the role emotional.


| INTRODUC TI ON
Colorectal cancer (CRC) is the third-most commonly diagnosed cancer in the world and the second-most common cause of cancer death after lung cancer, and its incidence among causes of death is increasing annually. [1][2][3] Surgery is the only radical treatment for advanced CRC, and laparoscopic surgery has been widely accepted as a standard surgical procedure for CRC. 4,5 In recent years, there have been an increasing number of reports of single-incision laparoscopic colectomy (SILC). [6][7][8][9][10][11][12][13][14] Single-incision laparoscopic surgery has been reported to be useful and safe for other organs, such as in cholecystectomy. 15,16 In the area of colectomy, the usefulness and safety of SILC compared with multiport laparoscopic colectomy (MPLC) have been clarified. Five randomized control trials (RCTs) comparing SILC and MPLC in colectomy have been published, including our previous report. [10][11][12][13][14] Those studies found no marked differences in the oncological or short-term outcomes between SILC and MPLC. We also previously reported no significant difference in the oncological outcomes between SILC and MPLC in our RCT. 10 In general, the advantages of SILC are considered to be a short wound length and improved cosmetic outcomes. However, the assessment of the cosmetic outcomes is a highly subjective evaluation. Maggiori et al 11 reported that there were no significant differences in the postoperative pain or health-related quality of life (HRQOL) at 6 months after surgery, although SILC had a significantly higher satisfaction with the scar aspect at 6 months after surgery. In contrast, in an RCT for SILC + 1, Wang et al 12 reported that there were no significant differences in patient satisfaction with the scar aspect.
There have been only a few studies comparing HRQOL and patient satisfaction between SILC and MPLC for CRC patients, and there are some differences in results between previous RCTs. Therefore, the effect of SILC on HRQOL and patient satisfaction is still unclear. We conducted a RCT comparing SILC and MPLC in colectomy for colon cancer and previously reported the main results. 10 Subsequently, we performed this examination to evaluate the benefit to HRQOL and patient satisfaction associated with these two approaches. This examination of subjective data was pre-planned in the original study protocol, and the data were collected as part of that trial.
This sub-study clarified the effect of SILC compared with MPLC for CRC on HRQOL and patient satisfaction, including wound pain and cosmetic outcomes.

| ME THODS
This was a pre-planned sub-study of an open-label, multicenter, randomized, prospective trial comparing SILC and MPLC. We previously reported the trial design and main results of this RCT. 10  The inclusion criteria were an age of 20-80 years, performance status ECOG 0-1, no bulky tumor (≤4.0 cm in diameter), no history of gastrointestinal surgery except appendectomy, and no organ dysfunction or blood abnormality. The exclusion criteria were multiple cancers (disease-free interval within 5 years), active infectious disease, severe comorbidities, medical history of mental and/or central nervous system disease, pregnant or lactating status, and preoperative treatment for colon cancer.
Randomization and data handling were performed by the Department of Biostatistics and Epidemiology Data Center of Yokohama City University. After confirming the inclusion/exclusion criteria and obtaining written informed consent, patients were randomized by means of computerized randomization following a fax to the data center on the morning of surgery. The allocated procedure was not concealed from the investigators or the patients. The sizes of the groups were balanced using the minimization method according to sex, age (<65 and ≥65 years old), and clinical stage (stage 0-II, III).

| Surgical procedure
All procedures were performed by five surgeons who had received endoscopic surgical skill accreditation for laparoscopic gastroenterological surgery from the Japan Society for Endoscopic Surgery. 17 In both arms, complete mesocolic excision (CME) with central vascular However, single-incision laparoscopic colectomy may be inferior than multiport laparoscopic colectomy in terms of the role emotional.

K E Y W O R D S
colorectal surgery, health-related quality of life, laparoscopic surgery, patient satisfaction, single-incision ligation (CVL) was performed. Other details of the SILC and MPLC procedures have already been reported. 10

| Outcomes and statistical analyses
The main outcome in this sub-study was the HRQOL score at 1 month after surgery. The primary outcome of this entire RCT was the incidence of postoperative complications within 30 days after surgery.
The sample size of this trial was determined as described below.
A power analysis determined that 95 patients would be required to demonstrate a reduction in the incidence of postoperative complications within 30 days from 25% to 10% at a significance level of 5% and power of 80%. Subsequently, 100 patients were randomly assigned to each group.
The HRQOL score was measured using the Japanese version of the 36-item Short Form Health Survey (SF-36) version 2.0, which was based on the Japanese National Reference. 18,19 The questionnaires were mailed to the patients before and 1 month after surgery.
The patients completed the questionnaires at home and then mailed it back to us.
The SF-36 is a tool used worldwide for measuring HRQ OL according to an inclusive standard and not a disease-specific standard. [20][21][22][23] A genetic instrument was believed to be better suited to this substudy than a disease-specific instrument because the assessment involved a wide range of disease processes. The SF-36 was translated into Japanese and validated for the general Japanese population. 18,19 This tool contains 36 questions. The score is expressed numerically In addition, the rate of change in each item of SF-36 before and after surgery was also examined. The proportion of patients with 10%, 15%, and 20% reduction of each score of the SF-36 from baseline were compared between the two groups respectively.
The secondary outcome in this sub-study was the patient satisfaction with the surgery and their postoperative clinical course.
Seven questions were asked regarding patients' satisfaction at 1 month after surgery, based on the five-case method. Patients who did not respond to all of the questions were excluded from this analysis.
We performed a post-hoc subgroup analysis for HRQOL at 1 month after surgery, stratified by the postoperative complications (Clavien-Dindo classification [CD] grade 0-I vs ≥II).
All continuous data in this article are presented as the median (interquartile range [IQR]). All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan 25 ), which is a graphical user interface for R (The R Foundation for Statistical Computing). Differences between categorical and continuous variables were tested with Pearson's chi-square test and the Mann-Whitney U test, respectively. The results of the SF-36 and the questions concerning the satisfaction of the patients were examined to determine whether or not they showed a normal distribution, but no obvious normality was observed. Therefore, non-parametric tests were performed to analyze the results of this sub-study.
Differences between continuous variables were tested using the Mann-Whitney U test when there was no correspondence between the two groups or Wilcoxon's signed rank test when correspondence was noted between the two groups. For the analysis of the questions concerning patient satisfaction by the five-case method, we considered the five answer items as ordinal variables and used the Mann-Whitney U test. P-values <.05 were considered statistically significant.  Table 1. The baseline factors were well-balanced, and the surgical outcomes were similar between the MPLC and SILC arms. After excluding 18 patients (9.0%) who did not complete the SF-36 questionnaire, 182 patients (91.0%) were ultimately included in the analysis of this sub-study (92 patients in the SILC group and 90 patients in the MPLC group).

| RE SULTS
The HRQOL scores before surgery (baseline) are presented in Figure 1A. There was no statistically significant difference between the two arms in all other subitems of SF-36, except for the BP. The preoperative BP was significantly lower in the SILC group than the MPLC group.
The HRQOL scores at 1 month after surgery are shown in Figure 1B. None of the subitems or component summary scores of the SF-36 differed significantly in the two arms. The changes in HRQOL before and after surgery are compared in the two arms respectively in Table 2. Among all subitems and component summary scores, the RP, BP, VT, and PCS were significantly lower at 1 month after surgery than before in both groups. The PF, GH, SF, MH, MCS, and RCS were not significantly different after surgery compared with before surgery in both groups. However, the RE was significantly lower after surgery than before only in the SILC group. Regarding the change rate of each item of SF-36 before and after surgery, the proportion of patients with 10%, 15%, and 20% score reduction was compared respectively but no significant difference was observed between the two groups (the data were not shown).
After excluding one patient who did not complete the questionnaire about patient satisfaction, 181 patients were included in the analysis of patient satisfaction (92 patients in the SILC group and 89 patients in the MPLC group). The patient satisfaction at 1 month after surgery is compared between the two arms in Table 3

| D ISCUSS I ON
In the present sub-study, we compared HRQOL assessed by the Japanese version of the SF-36 and the patient satisfaction between the SILC and MPLC among Japanese patients with cancer. There were no significant differences between SILC and MPLC for any of the subitems or component summary scores of the SF-36, except for the preoperative BP in the SILC group compared with the MPLC group. In addition, no significant differences were found between the two arms in any of the questionnaire items regarding patient satisfaction at 1 month after surgery.
Single-incision laparoscopic colectomy has the benefits of minimizing abdominal trauma from surgery for CRC. However, in a small pilot study that compared levels of biochemical markers between SILC and MPLC, the IL-6, IL-8, and CRP levels showed similar peaks and no significant differences. 26 In several meta-analyses comparing SILC and MPLC, SILC was suggested to be more beneficial in terms of blood loss, length of postoperative hospital stay, and wound length when performed by a skilled surgeon. 8,9 In several previous RCTs comparing SILC and MPLC, there were no significant differences in the short-term results, except for a shorter combined scar length with SILC. 10 11,12,14 In general, no significant differences have been reported in the short-term results, including with regard to other oncological results. We also previously reported that SILC had no clear benefit over MPLC in our own RCT. 10 Previous studies, including our own report, have mainly dealt with objective data, and only a few studies have compared subjective data, such as HRQOL and patient satisfaction, between SILC and MPLC. However, while all of the patients in that trial were CRC patients, they also all had a plus-1 port and may not necessarily reflect the results that might be achieved with pure SILC compared to MPLC. 12 Minimizing abdominal trauma may provide certain subjective benefits. However, the present sub-study found no statistically significant difference in HRQOL at 1 month after surgery between the two groups. Although preoperative BP between both groups was significantly lower in SILC, there was also no significant difference in postoperative BP between SILC and MPLC groups. There was no significant difference between the two groups in the preoperative information collected according to the protocol of this trial, and it was unclear why preoperative BP was lower in the SILC group than in the MPLC group. However, we also examined the rate of change in BP before and after surgery, but no significant difference was observed between the two groups. On assessing the RE, the RE significantly decreased before and after surgery only in the SILC group (Table 1).

TA B L E 1 Clinicopathological characteristics and surgical outcomes
Therefore, based on the present findings, SILC may be slightly inferior in terms of the RE than MPLC. In Japan, SILC is a technique that has been standardized, but it is not yet widespread and is not well known among the public population. Therefore, the satisfaction with conventional five-port laparoscopic colectomy may potentially be compared to open surgery rather than SILC. The present study also suggested that MPLC had a sufficiently high degree of satisfaction as surgery for colon cancer. Of note, a "single incision" may not be as great a concern to colon cancer patients as we surgeons think.
Immediately after surgery, patients' interest may be focused on whether the surgery was completed successfully and the cancer was treated. This vague anxiety about new procedures among the public, particularly a lack of surety concerning whether the cancer has been completely removed with a single incision, may be reflected in the significant reduction in RE after surgery in the SILC group.
In the result of this study, there was no significant difference in patient satisfaction, despite a significant difference in RE between the two groups. The RE scores of the SF-36 are low when there is a psychological problem when working or doing daily activities in the past 1 month. In our questionnaire of patient satisfaction, Q6 was the only item potentially associated with RE in SF-36. In addition, Q6 is also an item that asks about the inconvenience of daily life until discharge.
During hospitalization, there were not many such scenes in terms of work and daily activities, and it was considered that there are few RErelated situations. Since patients were discharged about a week after surgery, RE on activity over the past 1 month could be more strongly influenced by the 3 weeks spent at home. In addition, Q3 and Q4 seemed to be more closely related to MH than RE. These were considered to be the factors that did not make a difference in patient satisfaction despite a significant difference in RE only in the SILC group.  Third, the patients were not blinded, which might have influenced the outcomes. However, the authors believe that the findings of this study will provide a firm foundation for future studies.
In conclusion, SILC was similar to MPLC in terms of HRQOL and satisfaction among patients undergoing laparoscopic colectomy for cancer. However, SILC may be inferior in terms of RE.

D I SCLOS U R E
Funding: This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of Interest: The authors declare that they have no conflicts of interest.  TA B L E 4 Subgroup analysis of healthrelated quality of life scores at 1 mo after surgery, stratified by postoperative complication severity