The influence and countermeasure of obesity in laparoscopic colorectal resection

Abstract Background The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Methods Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ≥25 kg/m2 (n = 113) and those with a BMI <25 kg/m2 (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ≥28 kg/m2 who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m2) undertook a PWLP including caloric restriction and exercise for 29.6 (15–70) days. The effects of this program were evaluated. Results Study 1: The BMI ≥25 kg/m2 group had a prolongation of operation time and hospital stay than the BMI <25 kg/m2 group. Study 2: The patients achieved a mean weight loss of 6.9% (−6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ≥25 kg/m2 group. Conclusion Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR.


| INTRODUC TI ON
The prevalence of obesity is currently very high in Western countries, and has also increased in Asian countries, including Japan. 1 In laparoscopic surgery, obesity may reduce technical feasibility, prolong operative time, and increase operative blood loss. Therefore, obesity is a major risk factor for complications in laparoscopic surgery. [2][3][4] Some authors have reported that laparoscopic colectomy can be safely performed in overweight and obese patients. 5 However, others have reported that obese patients have a greater conversion rate to laparotomy, greater anastomotic leakage rate, and greater rate of complications compared with nonobese patients. 2,6 Furthermore, studies have reported that laparoscopic surgery for colorectal cancer is technically more difficult in obese patients than in nonobese patients. 2,7,8 Previous studies have reported that obesity is a risk factor for complications after rectal surgery. Heus et al 9 evaluated the influence of visceral obesity and muscle mass on postoperative complications in rectal surgery, and found that visceral obesity is correlated with a worse outcome after surgery for rectal cancer than body mass index (BMI), subcutaneous fat, and skeletal muscle area. Yamamoto et al 10 reported that an increased BMI might be a potential risk factor for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique. Anastomotic leakage is reportedly associated with poor oncologic outcomes, especially regarding disease-free survival. 11 Therefore, obesity is an important risk factor of the severe complications and poor oncological outcomes after laparoscopic colorectal surgery. Thus, there is a need for preoperative intervention for obese patients with colorectal cancer.
Regarding preoperative weight loss before cancer surgery, Inoue et al 12 reported that the preoperative 20-day very low-calorie diet weight loss program showed weight loss, reduction of visceral fat mass, and severe postoperative morbidity before laparoscopic gastrectomy for gastric cancer. In bariatric surgery, preoperative weight loss reduced the risk of postoperative complications and contributed to postoperative weight loss 13 . However, there were only a few reports about preoperative weight loss in colorectal surgery. The effect of preoperative weight loss remains unclear, especially in cancer surgery.
To minimize these issues in obese patients undergoing laparoscopic colorectal resection (LCR), a preoperative weight loss program (PWLP) was started in our department. The aim of the present study was to investigate the influence of obesity on complications in LCR, and to investigate the usefulness of a PWLP for obese patients undergoing LCR. Hartmann's operation (n = 4), total colectomy (n = 1), or temporary diverting stoma (n = 19) were excluded in this series. In total, 392 patients who underwent LCR with D2 or D3 lymph node dissection for colorectal cancer were enrolled in this study. All cancers were staged based on the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma. 14 The patients were divided into two groups: those with a BMI of ≥25 kg/m 2 (BMI ≥25 kg/m 2 group; n = 113) and those with a BMI of <25 kg/m 2 (BMI < 25 kg/m 2 group; n = 279). The patient background data are shown in Table 1.

| Study 2: Evaluation of a PWLP for laparoscopic colorectal resection
To improve the operative outcomes in obese patients, a PWLP was started in the Department of Surgery, Tokushima University, with the approval of a suitably constituted Ethics Committee of Tokushima University Hospital (Figure 1).
The indications for a PWLP at Tokushima University Hospital were a BMI ≥28 kg/m 2 , early colorectal cancer (tumor depth ≤muscularis propria), and a planned LCR. Written informed consent was provided by each patient before surgery. The exclusion criteria were conditions associated with poor compliance (e.g., psychiatric illness).
There were no dropped out patients in this study.
The PWLP comprised caloric restriction (total 1200 kcal per day) and exercise (matched age and activities of daily living) for 29.6 (15-  Table 2 shows the characteristics of the patients in the PWLP. The PWLP participants were patients with a BMI of ≥28 kg/m 2 who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m 2 ). These PWLP participants were enrolled from 2016 to 2019. To confirm the tumor progression in PWLP, we checked tumor marker, computed tomography, and colonoscopy in pre-and post-PWLP. There was no tumor progression in all patients who underwent PWLP.
General clinical and clinicopathological data from each eligible patient were retrieved from the medical reports. All data were reviewed retrospectively, and the Clavien-Dindo classification was used to evaluate the short-term complication rate during hospitalization.

| Statistical analysis
The unpaired/paired Student's t-test or the Mann-Whitney U-test was used for the statistical analysis of the continuous variables, while the chi-square test was used for the categorical variables. In all three statistical tests, P < .05 was considered to represent a signifi-  Table 3 shows the operation times and intraoperative blood loss in the BMI ≥25 kg/m 2 and BMI <25 kg/m 2 groups. The operation time of the BMI ≥25 kg/m 2 group was significantly longer than that of the BMI <25 kg/m 2 group. Postoperative complications of Clavien-Dindo grade II and anastomotic leakage did not significantly differ between the two groups. The duration of postoperative hospitalization of the BMI ≥25 kg/m 2 group was significantly longer than that of the BMI <25 kg/m 2 group. Hospital stay (days) 23.6 (6-382) 17.6 (6-85) <.05

| Study 1: The influence of BMI in laparoscopic anterior resection
Note: The Mann-Whitney U-test was used for the statistical analysis of continuous variables. P < .05 was considered to indicate a significant difference. Continuous variables are expressed as the mean ± standard deviation.
Abbreviation: BMI, body mass index. Table 4 shows the comparison of with and without postoperative complication and anastomotic leakage in laparoscopic colorectal resection. In the complication group, there was a significantly higher prevalence of rectum, operation time ≥300 minutes, and blood loss ≥100 mL.
In the anastomotic leakage group, there was a significantly higher prevalence of rectum and operation time ≥300 minutes were independent risk factors of anastomotic leakage. Regarding postoperative complication, blood loss ≥100 mL was an independent risk factor in multivariate analysis. Furthermore, rectum and operation time 300 ≥minutes were independent risk factors of anastomotic leakage (Table 5).

| Study 2: Evaluation of a PWLP for laparoscopic colorectal resection
The patients achieved a mean weight loss of 6.9% (−6.0 kg) after the PWLP. Compared with the pre-PWLP values, the mean post-PWLP VFA and body fat mass were significantly decreased (mean VFA decrease 18.0%; mean body fat mass decrease 9.3%), whereas the skeletal muscle mass was unchanged.
Regarding the obesity-related parameters, the mean total cholesterol was significantly decreased after the PWLP. However, the mean pre-and post-PWLP albumin values did not significantly differ (Table 6). Table 7 shows the comparison of operative outcomes between the BMI ≥25 and PWLP group. In the BMI ≥25 group of Table 7, the cases of fStageIII, IV (n = 38) were excluded to match the tumor progression. The PWLP group showed a lower prevalence of postoperative complications (including anastomotic leakage) compared with the BMI ≥25 kg/m 2 group. There was no significant difference in operation time and postoperative hospital stay between the two groups ( Table 7).

| D ISCUSS I ON
The present study was designed to investigate the influence of obesity on LCR for colorectal cancer, and to evaluate the usefulness of  Note: The Mann-Whitney U-test was used for the statistical analysis of continuous variables. P < .05 was considered to indicate a significant difference.
a PWLP for obese patients undergoing LCR for colorectal cancer.
The BMI ≥25 kg/m 2 group had a significantly longer operation time and postoperative hospital stay than the BMI <25 kg/m 2 group.
The PWLP group achieved significant decreases in body weight and VFA. Furthermore, the PWLP group had a lower prevalence of postoperative complications compared with the BMI ≥25 kg/m 2 group.
For patients undergoing laparoscopic sleeve gastrectomy, a preoperative diet comprising immune-enhancing nutrition formulas reportedly achieves greater preoperative weight loss, lower postoperative pain, and lower levels of C-reactive protein and liver enzymes than high-protein formulas or a regular diet with similar caloric intakes. 15 However, one of the important problems with weight loss is the incidence of sarcopenia. A decrease in skeletal muscle, referred to as sarcopenia, is reportedly correlated with morbidity and mortality in patients undergoing digestive surgery. Thus, unintentional weight loss can be used to predict mortality and morbidity rates in colorectal surgery. In particular, preoperative weight loss is significantly associated with cardiopulmonary complications. 16  Therefore, the duration of the PWLP may be reasonable for the purpose of decreasing postoperative complications.
The limitations of this study were that it was a retrospective study, single institution, and a small number of patients. In addition, the comparison between the PWLP group and the no-PWLP group in the same background was not done.
In conclusion, obesity affected the operative outcomes in LCR.
A PWLP may be useful for obese patients undergoing LCR, and a PWLP may be useful in minimizing complications for obese patients undergoing LCR.

ACK N OWLED G M ENTS
The authors thank the staff at the Department of Surgery, Institute Hospital stay (days) 14.0 (6-382) 15.0 (9-28) .56 Note: The Mann-Whitney U-test was used for the statistical analysis of continuous variables. P < .05 was considered to indicate a significant difference.

TA B L E 7
Comparison of operative outcomes between the BMI >25 and PWLP group