Observational Study Medicine ®

OPEN

Effect of perioperative oral management on the

prevention of surgical site infection after
colorectal cancer surgery
A multicenter retrospective analysis of 698 patients via analysis of
covariance using propensity score
∗
Hiroshi Nobuhara, DDS, PhDa, Souichi Yanamoto, DDS, PhDb, , Madoka Funahara, DDS, PhDc,
Yasuhiro Matsugu, MD, PhDd, Saki Hayashida, DDS, PhDb, Sakiko Soutome, DDS, PhDe,
Akiko Kawakita, DDS, PhDb, Satoshi Ikeda, MD, PhDd, Toshiyuki Itamoto, MD, PhDd,
Masahiro Umeda, DDS, PhDb

Abstract
Surgical site infection (SSI) is 1 of the frequent postoperative complications after colorectal cancer surgery. Oral health care has been
reported to reduce the risk of SSI or postoperative pneumonia in oral, esophageal, and lung cancer surgeries. The purpose of the
study was to investigate the preventive effect of perioperative oral management on the development of SSI after a major colorectal
cancer surgery.
The medical records of 698 patients who underwent colorectal cancer surgery at 2 hospitals in Japan were reviewed. Among these
patients, 563 patients received perioperative oral management (oral management group) and 135 did not (control group). Various
demographic, cancer-related, and treatment-related variables including perioperative oral management intervention and the
occurrence of SSI were investigated. The relationship between each variable and the occurrence of SSI was examined via univariate
and multivariate analyses using Fisher exact test, 1-way analysis of variance (ANOVA), and logistic regression. The occurrence of SSI
in the 2 groups was evaluated via logistic regression using propensity score as a covariate. The difference in mean postoperative
hospital stay between the oral management and control groups was analyzed using Student’s t test.
SSI occurred in 68 (9.7%) of the 698 patients. Multivariate analysis showed that operation time, blood loss, and perioperative oral
management were significantly correlated with the development of SSI. However, after the propensity score analysis, not receiving
perioperative oral management also became a significant risk factor for SSI. The odds ratio of the oral management group was 0.484
(P = .014; 95% confidence interval: 0.272–0.862). Mean postoperative hospital stay was significantly shorter in the oral management
group than in the control group.
Perioperative oral management reduces the risk of SSI after colorectal cancer surgery and shortens postoperative hospital stay.
Abbreviations: ALT = alanine aminotransferase, BMI = body mass index, CDC = Centers for Disease Control and Prevention,
CRP = C-reactive protein, ERAS = enhanced recovery after surgery, SSI = surgical site infection.
Keywords: colorectal cancer surgery, oral management, propensity score, surgical site infection

1. Introduction
Editor: Li Wu Zheng. Perioperative oral management has been performed in patients
The authors have no conflicts of interest to disclose. undergoing cancer surgery as perioperative management using a
a
Department of Dentistry and Oral and Maxillofacial Surgery, Hiroshima team approach involving nutrition management, medicines
Prefectural Hospital, Hiroshima, b Department of Clinical Oral Oncology, Nagasaki management, and rehabilitation teams. Some investigators have
University Graduate School of Biomedical Sciences, Nagasaki, c Kyushu Dental
University School of Oral Health Sciences, Fukuoka, d Department of
reported the preventive effect of perioperative oral management
Gastroenterological, Breast and Transplant Surgery, Hiroshima Prefectural on postoperative pneumonia and surgical site infection (SSI) after
Hospital, Hiroshima, e Perioperative Oral Management Center, Nagasaki esophageal, cardiac, and oral cancer surgeries and thoracic
University Hospital, Nagasaki, Japan. surgery.[1–7] However, there are only a few studies with high
∗
Correspondence: Souichi Yanamoto, Department of Clinical Oral Oncology, evidence level; therefore, the recommendations of the Centers for
Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Disease Control and Prevention (CDC) Guideline[8] and
Nagasaki, 852-8588, Japan (e-mail: [email protected]).
enhanced recovery after surgery (ERAS) program[9] do not
Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.
contain the description of oral management.
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is Although the fasting period after digestive surgery has recently
permissible to download, share, remix, transform, and buildup the work provided been shortened due to the introduction of the ERAS program,
it is properly cited. The work cannot be used commercially without permission digestive surgery is still longer than other types of surgery; thus,
from the journal. there is an increase in oral bacteria after surgery. Therefore,
Medicine (2018) 97:40(e12545) perioperative oral management is considered especially impor-
Received: 3 May 2018 / Accepted: 30 August 2018 tant in patients who are to undergo digestive surgery, but there
http://dx.doi.org/10.1097/MD.0000000000012545 have been only a few reports regarding the appropriate oral

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Nobuhara et al. Medicine (2018) 97:40 Medicine

management methods and their effectiveness in the prevention of 5) serum laboratory data before surgery (albumin, alanine
postoperative complications. aminotransferase [ALT], creatinine, and C-reactive protein
SSI is 1 of the most frequent postoperative complications after (CRP)),
major gastrointestinal surgeries,[10] especially after colorectal 6) site of cancer (colon/rectum),
cancer surgery; its occurrence and severity are generally known to 7) operation time,
be relatively high.[11,12] SSI leads to a longer hospital stay, 8) blood loss,
decrease in quality of life, increased medical cost, as well as 9) method of surgery (laparoscopic surgery versus laparoto-
mortality of patients; therefore, recommendations have been my),
proposed for its prevention.[13,14] According to the CDC 10) occurrence of SSI, and
Guideline, it is recommended to whenever possible, identify 11) postoperative hospital stay.
and treat all infections remote to the surgical site before elective
operation and postpone elective operations on patients with
2.4. Statistical analysis
remote site infections until the infection has resolved.[8] One of
the most frequent remote infections is an intraoral infectious Statistical analyses were performed using software (SPSS version
lesion such as periodontal disease of periapical periodontitis. 24.0; Japan IBM Co., Tokyo, Japan). First, the correlation
We previously reported that perioperative oral management between each variable and SSI occurrence in the 698 patients was
reduced the occurrence of postoperative pneumonia in patients analyzed using Fisher exact test and 1-way analysis of variance
who underwent esophageal cancer surgery.[1,2] The purpose of (ANOVA), followed by multivariate logistic regression analysis
the current study was to investigate whether perioperative oral using stepwise selection. Mean hospital stay in the oral
management can prevent SSI after colorectal cancer surgery using management and control groups was compared using Student
a multicenter retrospective study with a large sample size. t test. In all the analyses, a 2-tailed P value <.05 was considered
statistically significant.
2. Materials and methods Subsequently, propensity score analysis was performed to
reduce the selection bias associated with retrospective data. A
2.1. Patients propensity score was calculated for each patient using logistic
regression with the following variables: age, gender, BMI,
This retrospective cohort study included all patients who
diabetes, hypertension, heart disease, serum albumin, ALT,
underwent colorectal cancer surgery with curative intent at
creatinine, CRP, operation time, blood loss, tumor site, and
Hiroshima Prefectural Hospital or Nagasaki University Hospital
operation method. The oral management group was compared to
between 2014 and 2016. The exclusion criteria were palliative
the control group using logistic regression analysis with
surgery, transanal endoscopic surgery, and emergency surgery.
propensity score as a covariate.
After excluding patients with inadequate or unknown informa-
tion, the remaining 698 patients were eligible for inclusion.
The standard infection control methods were performed 2.5. Ethics
according to the recommendation of CDC Guideline.[8] Patients
This study was approved by the institutional review board of
received administration of antibiotics such as cefmetazole,
Nagasaki University Hospital (N0. 17082139). This was a
flomoxef, or cefazolin plus metronidazole during surgery and
retrospective study, and therefore we published research plan and
for 24 to 48 hours postoperatively.
guaranteed opt-out opportunity by the homepage of our hospital
according to instruction of the institutional review board.
2.2. Oral management intervention
Among a total of 698 patients, 563 received perioperative oral 3. Results
management by dentists and dental hygienists immediately after
their referral to the dentistry department. The oral management Table 1 shows the background data of the 563 patients in the oral
consisted of instructions regarding self-care, extraction of management group and the 135 patients in the control group.
infected teeth, removal of dental plaques and calculus (scaling), There was some bias between the 2 groups regarding heart
professional mechanical teeth cleaning, removal of tongue disease, albumin, creatinine, CRP, and surgical method. More
coating, and cleaning of dentures. Self-care instructions included patients in the oral management group underwent laparotomy
teeth brushing, interdental brushing, dental flossing, tongue than in the control group. The mean operation time and blood
brushing, denture brushing, and gargling. A total of 335 patients loss did not differ significantly between the groups.
received professional oral management 2 or more times before SSI occurred in 68 (9.7%) of the 698 patients. Using univariate
surgery, and 228 patients received it once. The remaining 135 analysis, operation time, blood loss, and oral management
patients did not receive the perioperative oral management intervention were significantly correlated with the occurrence of
intervention. SSI (Table 2). Multivariate analysis showed that operation time,
blood loss, and oral management intervention were significantly
correlated with SSI (Table 3). The odds ratio of the patients who
2.3. Variables received oral management was 0.428 (P = .003; 95% confidence
The following variables were examined using the patients’ interval [CI]: 0.244–0.749). Further, from the propensity score
medical records; analysis, oral management intervention significantly reduced the
1) age, risk of SSI (Table 4). The odds ratio of the oral management
2) gender, group was 0.484 (P = .014; 95% CI: 0.272–0.862).
3) body mass index (BMI), Regarding the relationship between the frequency of oral care
4) general complications (diabetes, hypertension, and heart and SSI prevention, patients who received 2 or more oral
disease), management sessions had a lower frequency of SSI and

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Table 1
Demographic characteristics of the oral management and control groups (698 patients).
Variable Oral management group (n = 563) Control group (n = 135) P value
Age (years) 68.3 ± 11.6 69.9 ± 11.5 .166
Gender male 305 77 .565
female 258 58
BMI (kg/m2) 22.4 ± 3.46 22.2 ± 3.45 .446
Diabetes (-) 450 104 .478
(+) 113 31
Hypertension (-) 308 74 .478
(+) 255 61
∗
Heart disease (-) 534 112 <.001
(+) 29 23
∗
Albumin (g/dL) 3.91 ± 0.505 3.80 ± 0.661 .024
ALT (U/L) 19.9 ± 17.4 19.6 ± 14.6 .831
∗
Creatinine (mg/dL) 0.862 ± 0.700 1.08 ± 1.29 .007
∗
CRP (mg/dL) 0.620 ± 1.44 0.940 ± 2.16 .037
Operation time (minute) 280 ± 98.4 297 ± 114 .081
Blood loss (g) 158 ± 259 150 ± 235 .724
Site colon 376 91 .919
rectum 187 44
∗
Operation method laparoscopic surgery 340 107 <.001
laparotomy 223 28
ALT = alanine aminotransferase, BMI = body mass index, CRP = C-reactive protein.
∗
significant values are expressed as means ± standard deviation or number.

significantly shorter postoperative hospital stay than those who are known to influence various general diseases, such as
received only 1 oral management session (Table 5). pneumonia,[18] cardiovascular[19] and cerebrovascular dis-
ease,[20] rheumatoid arthritis,[21] preterm birth or low-weight
birth,[22] and carcinogenic[23] and non-alcoholic steatohepati-
4. Discussion
tis.[24] Some investigators reported that Fusobacterium nuclea-
The oral cavity has been recognized as a significant reservoir of tum, 1 of the periodontal pathogens, or deep periodontal pockets
pathogenic microorganisms, which cause the infection of might influence the development of colon cancer.[25–27]
multiple organs[15–17]; therefore, quantitative and qualitative Regarding the mechanism by which oral bacteria affect general
control of oral bacteria via oral health care is considered disease, 4 factors have been considered. First, direct transfer of
important for the prevention of infectious diseases. Oral bacteria oral bacteria may cause SSI after head and neck cancer surgery,

Table 2
Univariate analysis of the relationship between each variable and the occurrence of surgical site infection.
Variable SSI (-) SSI (+) P value
Age (years) 68.8 ± 11.4 67.3 ± 12.8 .324
Sex male 341 41 .370
female 289 27
BMI (kg/m2) 22.4 ± 3.43 22.0 ± 3.68 .404
Diabetes (-) 498 56 .636
(+) 132 12
Hypertension (-) 342 40 .523
(+) 288 28
Heart disease (-) 584 62 .627
(+) 46 6
Albumin (g/dL) 3.90 ± 0.538 3.79 ± 0.559 .098
ALT (U/L) 19.9 ± 17.2 19.7 ± 13.5 .942
Creatinine (mg/dL) 0.888 ± 0.775 1.06 ± 1.37 .115
CRP (mg/dL) 0.684 ± 1.63 0.663 ± 1.38 .917
∗
Operation time (minute) 278 ± 97.2 334 ± 128 <.001
∗
Blood loss (g) 141 ± 225 303 ± 420 <.001
Site colon 429 38 .057
rectum 201 30
Operation method laparoscopic surgery 406 41 .508
laparotomy 224 27
∗
Oral management intervention ( ) 112 23 .003
(+) 518 45
ALT = alanine aminotransferase, BMI = body mass index, CRP = C-reactive protein, SSI = surgical site infection.
∗
significant values are expressed as means ± standard deviation or number.

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Table 3 management should be started not just before surgery but as soon
Multivariate analysis of the variables related to surgical site as surgery is decided.
infections in the 698 patients. In digestive surgery, the prevention of postoperative complica-
tions has advanced due to the spread of minimally invasive surgeries
Variable P value Odds ratio 95% CI
∗ such as laparoscopic surgery and progression in perioperative
Operation time (minute) .030 1.003 1.000–1.005 management. However, factors that increase postoperative
∗
Blood loss (g) .002 1.001 1.000–1.002 complications such as the expansion of the indication for surgery
∗
Oral management (+) vs. ( ) .003 0.428 0.244–0.749
to elderly patients with various general diseases and increase in
intervention
drug-resistant bacteria. Perioperative oral management, which
CI = confidence interval.
∗
controls the bacterial flora in the mouth and reduces oral infectious
significant stepwise selection. lesions from the significance of treatment of remote infection before
surgery, may play an important role in perioperative management.
Table 4 We believe further investigation is necessary to standardize oral
Propensity score analysis of the association between oral management methods and verify their effectiveness.
management intervention and the development of surgical site In the current study, multivariate analysis revealed that
infection. operation time, blood loss, and oral management intervention
Oral management group versus were independent risk factors for SSI. Because of the retrospective
control group P value Odds ratio 95% CI nature of the study, it was necessary to align background factors
between the 2 groups. Therefore, we applied propensity score
Univariate analysis (baseline) .002 0.423 0.246–0.728
matching analysis. However, since there was a large difference in
Multivariate analysis (baseline) .003 0.428 0.244–0.749
After adjustment using propensity .014 0.484 0.272–0.862
sample size between the non-intervention and intervention
score analysis groups many subjects were excluded, and the decrease in the
generalizability of the findings became a problem. To solve these
CI = confidence interval. problems, we observed the onset of SSI using a model containing
a propensity score, calculated as the oral management interven-
Table 5 tion, as a covariate in the multivariate analysis (binomial logistic
Differences in preventive effect based on the number of regression analysis), and it was shown that when oral care was
perioperative oral management sessions. administered, SSI onset reduced by 0.484 times with a significant
probability of 0.014.
Number of oral Occurrence of surgical Postoperative
management site infection hospital stay However, this study had several weaknesses. First, because it
was retrospective, there was the possibility of unknown

] ]
0 23/135 (17.0%) ∗
∗
15.7 days ]0.13 ∗ confounding factors despite the propensity matching analysis.
1 21/228 (9.21%) ]0.031 0.002 14.1 days ∗ <0.001
Specific dental indicators such as periodontal indexes (probing
2 or more 24/335 (7.16%) ]0.429 10.7 days ]0.001
depth), caries indexes (DMFS; Number of decayed, missing, or
∗
significant values are expressed as means±standard deviation or number. filled surfaces), alveolar bone loss, and indexes of oral hygiene
(plaque score) could not examined because it is a retrospective
SSI after upper digestive tract cancer surgery, and postoperative study and such information was not described in the medical
aspiration pneumonia. Second, intravascular invasion of odon- records. Second, since the 2 hospitals do not have a unified oral
togenic bacteremia and transition to remote organs by blood care protocol, it is not clear which of the procedures was effective
vessel or lymph duct may cause SSI of various sites of surgeries. in the prevention of SSI. Perioperative oral management has been
Third, blood transfer of endotoxin or inflammatory cytokine by included in the Japanese medical insurance system since 2012,
oral bacteria may influence to remote organs. And fourth, and most Japanese patients now receive oral management before
swallowing pathogenic microorganism of the oral cavity may cancer surgery. Thus, it would be challenging to conduct a
change of intestinal flora and disorder of intestinal barrier randomized controlled trial on the protective effect of periopera-
function. Among them, we believe odontogenic bacteremia, tive oral management. We believe that based on the results of this
which could cause infection after colorectal cancer surgery is study, it can be concluded that perioperative oral management
especially important. Moreover, it is known that transient may reduce the risk of SSI after colorectal cancer surgery.
bacteremia often occurs in patients with severe periodontal In summary, our retrospective investigation of 698 patients
disease.[28] The CDC Guideline for the prevention of SSI[8] with colorectal cancer undergoing surgery suggested the effects of
describes that preoperative infectious lesions in a remote site perioperative oral management on prevention of SSI.
became a risk factor for SSI; therefore, these lesions should be
treated before surgery. Although urinary tract or respiratory tract
Acknowledgments
infections are frequently problematic as remote infections, there
are oral infectious lesions such as in periodontal disease that is The authors would like to thank Editage (www.editage.jp) for
more problematic than these remote infections. English language editing.
The current study indicates that not receiving perioperative
oral management is 1 of the risk factors associated with the
Author contributions
development of SSI. Furthermore, it shows that receiving 2 or
more oral management sessions is more effective than receiving Data curation: Madoka Funahara, Masahiro Umeda.
only 1 management session. This is possibly because the effect of Formal analysis: Hiroshi Nobuhara.
preventing periodontal inflammation and enhancing self-care Investigation: Hiroshi Nobuhara, Madoka Funahara, Yasuhiro
capacity using 2 or more oral interventions is high compared to a Matsugu, Saki Hayashida, Sakiko Soutome, Akiko Kawakita,
single intervention. These findings suggest that perioperative oral Satoshi Ikeda, Toshiyuki Itamoto.

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