Mechanical and oral antibiotics bowel preparation for elective rectal cancer surgery: A propensity score matching analysis using a nationwide inpatient database in Japan

Abstract Aim The best bowel preparation method for rectal surgery remains controversial. In this study we compared the efficacy and safety of mechanical bowel preparation (MBP) alone and MOABP (MBP combined with oral antibiotic bowel preparation [OABP]) for rectal cancer surgery. Methods In this retrospective study we analyzed data from the Japanese Diagnosis Procedure Combination (DPC) database on 37 291 patients who had undergone low anterior resection for rectal cancer from 2014 to 2017. Propensity score matching analysis was used to compare postoperative outcomes between MBP alone and MOABP. Results A total of 37 291 patients were divided into four groups: MBP alone: 77.7%, no bowel preparation (NBP): 16.9%, MOABP: 4.7%, and OABP alone: 0.7%. In propensity score matching analysis with 1756 pairs, anastomotic leakage (4.84% vs 7.86%, P < 0.001), small bowel obstruction (1.54% vs 3.08%, P = 0.002) and reoperation (3.76% vs 5.98%, P = 0.002) were less in the MOABP group than in the MBP group. The mean duration of postoperative antibiotics medication was shorter in the MOABP group (5.2 d vs 7.5 d, P < 0.001) than in the MBP group. There was no significant difference between the two groups in the incidence of Clostridium difficile (CD) colitis (0.40% vs 0.68%, P = 0.250) and methicillin‐resistant Staphylococcus aureus (MRSA) colitis (0.11% vs 0.17%, P = 0.654). There was no significant difference in in‐hospital mortality between the two groups (0.00% vs 0.11% respectively, P = 0.157). Conclusion MOABP for rectal surgery is associated with a decreased incidence of postoperative complications without increasing the incidence of CD colitis and MRSA colitis.


| INTRODUC TI ON
The use of mechanical bowel preparation (MBP) in combination with oral antibiotic bowel preparation (OABP) before colorectal surgery has been discussed since the 1970 s. 1 Recently, guidelines based on systematic reviews and reviews on bowel preparation for colorectal surgery have been published around the world. [2][3][4][5] Those guidelines recommended MBP with OABP (MOABP) based on several reviews showing that MBP alone did not prevent postoperative complications and may be harmful, [6][7][8][9] while MOABP reduced postoperative complications after colorectal surgery. 10,11 Evidence of bowel preparation for colorectal surgery is increasing, but there are still few studies focused on rectal surgery. Actually, the Enhanced Recovery After Surgery (ERAS) Society indicated that MBP alone should not be used routinely in colonic surgery, but may be used for rectal surgery. 4 The risk of anastomotic leakage after rectal surgery is higher than that after colon surgery, and the method of anastomosis is different between colon and rectal surgery. More evidence is needed about appropriate bowel preparation for rectal surgery.
In addition, many surgeons have chosen MBP rather than MOABP in spite of recommendations by the guidelines. One of the reasons is that surgeons concern about enteritis caused by OABP such as Clostridium difficile (CD) colitis and methicillin-resistant Staphylococcus aureus (MRSA) colitis. 12,13 On the other hand, it has been reported that the incidence of CD colitis and MRSA colitis did not increase if oral antibacterial agents are used properly. 14,15 There are no studies that investigated the bowel preparation for rectal surgery using a nationwide database. We need to research which bowel preparations for rectal surgery are performed in a real-world and which bowel preparations are useful and safe. In this study we evaluated the current status of bowel preparation for rectal cancer surgery and the efficacy and safety of MOABP compared with MBP in a real-world setting using the Japanese Diagnosis Procedure Combination (DPC) database.

| Data source
In this nationwide retrospective study, we used the DPC database from January 2014 to December 2017. It contains discharge abstracts and administrative reimbursement claim data from inpatient cases collected at participating hospitals, and it has been used in various studies 16,17 The data were collected by the DPC Research Institute (a nonprofit organization) in collaboration with the Ministry of Health, Labor, and Welfare of Japan. The database includes the following data: disease names, hospitalization costs, comorbidities at admission and during hospitalization, coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10), age, sex, length of hospital stay, medical procedures including surgery, names and quantities of medicines administered, and discharge status (including in-hospital deaths). 18 Medical procedures are indexed with a Japanese code (K-code), 19

| Patient selection
Inclusion criteria were as follows: inpatient status and admission for rectal cancer (ICD-10 code: C20), and underwent low anterior

| Endpoints
Endpoints were as follows: in-hospital mortality, 30-d postoperative mortality, necessity of reoperation with general anesthesia, rate of surgical wound dehiscence, rate of anastomotic leakage, rate of postoperative small bowel obstruction needing a trans-nasal long decompression tube, necessity of perioperative transfusion, rate of CD colitis, rate of MRSA colitis, length of hospital stay (LOS), duration of postoperative antibiotic administration and total hospitalization cost.

| Statistical analysis
We conducted propensity score-matched (PSM) analysis to compare the efficacy of MOABP with that of MBP. We used the following variables for PSM: sex, age, body mass index (BMI), clinical TNM stage, rate of diverting stoma, rate of laparoscopic surgery, smoking, the use of antidiabetic drugs, oral corticosteroid drugs, oral antiplatelet drugs, and oral anticoagulant drugs in the admission and hospital volume. The hospital volume, which was used as a hospital-level factor, was defined as the annual number of LAR executed at each facility and categorized into quartiles (low volume: <54 cases, medium volume: 55-95 cases,

| The current status of bowel preparation
During the study period, 51 010 patients who underwent low anterior resection for rectal cancer were registered in the DPC database. The other groups were as follows: The NBP group 16.9%, the OABP group 0.7%, and the MOABP group 4.7%.

| Patient characteristics
Patient characteristics of each group are shown in Table 1. The NBP group tended to include advanced clinical TNM stage (Stages III or IV) patients and patients who underwent LAR at very high-volume hospitals. The MOABP group tended to be higher for the laparoscopic surgery rate than other groups and included patients who underwent LAR at high or very high-volume institutions. Table 2

| Comparison of postoperative outcomes between MOABP and MBP after propensity score matching
The patient characteristics after PSM are summarized in Table 3.
A total of 1756 pairs were matched (Figure 1). We confirmed that the characteristics of both groups were similar after PSM. The postoperative outcomes after PSM are shown in Table 4 In this study we found that the MBP group was the majority and accounted for 77.7% among all bowel preparation types. On the other hand, the MOABP group accounted for only 4.7%. Regarding the patient characteristics between the MBP group and the MOABP group, there was a notable difference in the rate of patients who underwent LAR at the high or very high-volume hospitals. We found that surgeons at high or very high-volume hospitals tended to choose MOABP more frequently. The high rate of laparoscopic surgery in the MOABP group is thought to be affected by hospital volumes. The NBP group accounted for 16.9%. The NBP group included more cases of advanced cancer. It is expected that the NBP group included many patients who could not receive MBP because of the possibility of intestinal obstruction caused by MBP. Along with that, the postoperative outcomes of the NBP group also seem to be worse than the MBP group and the MOABP group. We could not match the NBP group and other groups statistically because there were many factors that could not be adjusted. Furthermore, as we were concerned that patients of the NBP group had many factors that affect postoperative outcomes, we did not include this group for further comparison.  is a lack of detailed information regarding the bowel preparation.
For example, the duration of preparation and the dose are not included.
In conclusion, our investigation using real-world data highlight the effectiveness of MOABP for elective rectal cancer surgery.
MOABP decreased the incidence of anastomotic leakage, postoperative small bowel obstruction, and reoperation without increasing the incidence of CD colitis and MRSA colitis.

ACK N OWLED G M ENTS
The authors thank all data managers and hospitals participating in the Japanese Diagnosis Procedure Combination (DPC) database for their great effort in collecting data. No preregistration exists for the reported studies in this article.