Recent advancements in surgical techniques, surgical instruments, adjuvant chemotherapy [16], and perioperative management, such as the ERAS programme [17], have improved the outcomes of gastrointestinal surgery. Nevertheless, the incidence of infectious complications, such as SSIs, has not been significantly attenuated despite the introduction of an ERAS programme [18]. The incidence of perioperative complications, including SSIs, is higher in PDAC surgery than in other gastrointestinal surgeries [19]. In this study, we investigated the preventive effects of perioperative oral care on the incidence of postoperative SSIs in patients with PDAC. We observed that perioperative oral care for PDAC significantly reduced the incidence of SSIs and that poor oral hygiene was a risk factor for SSIs. Notably, multivariate analysis revealed that the absence of oral care intervention was a risk factor for SSIs, in addition to, a soft pancreas, the surgical procedure (PD), diabetes mellitus, and intraoperative blood transfusion. A soft pancreas is a major risk factor for POPF [20] and has a higher likelihood of progressing to organ/space SSIs. Compared to DP, PD is a more complex and invasive procedure, and patients undergoing PD have a higher risk of biliary tract infections and SSIs [21]. Diabetes mellitus is a well-known risk factor for postoperative infections [22], and blood transfusion has also been reported as a risk factor for postoperative SSIs in pancreatic cancer [23]. Therefore, our findings suggest that, in addition to previously reported risk factors for SSIs in PDAC, the absence of oral care intervention is a novel independent risk factor for SSIs.
Our analysis revealed that perioperative oral care did not significantly reduce the incidence of pneumonia and bacteraemia, which are infectious complications distinct to SSIs. The lower incidence of pneumonia and bacteraemia compared to that of SSIs, and a previous report [24], may have obscured any differences. Future studies should investigate the preventive effects of perioperative oral care on the incidence of pneumonia and bacteraemia using larger sample sizes.
Michaud et al. [25] indicated five routes of bacterial dissemination from the oral cavity to the pancreas, namely the general circulation, lymphatic system, duodenum, biliary duct, and bacterial translocation (BT) from the intestinal tract. Similar to the intestinal tract, the oral cavity acts as a reservoir of pathogenic microorganisms that cause systemic infections [26]. Oral bacteria, predominantly periodontal pathogens, adversely affect systemic diseases, such as cardiovascular disease, diabetes mellitus, rheumatoid arthritis, pneumonia, adverse pregnancy outcomes, and carcinogenesis [27, 28].
More advanced periodontal disease is associated with a greater risk of transient bacteraemia and endotoxemia during chewing movements and tooth brushing [29, 30]. In patients with severe periodontal disease, endotoxin activity in the blood during mastication is several times higher than that before mastication [30]. In addition, periodontal pathogens, such as Porphyromonas gingivalis, have been detected in 8–17% of submandibular and submental lymph nodes without cancer cell infiltration during head and neck cancer surgery [31]. Alverdy et al. [32] proposed that pathogenic microorganisms present in the oral cavity and intestinal tract are taken up by neutrophils and macrophages and transported to the surgical site, causing SSIs (Trojan Horse hypothesis). This mechanism may at least partly underpin the preventive effects of perioperative oral care on SSIs during major surgeries [32]. These reports suggest that, although the oral cavity (a hotbed of periodontal disease) is part of the same gastrointestinal tract as the gut, it is equally or even more prone to BT than the gut. We conjecture that perioperative oral care reduced BT from the oral cavity by decreasing the number of bacteria in the periodontal pockets and attenuating inflammation of the periodontal tissues, which in turn reduced the occurrence of SSIs.
Alternatively, controlling the number of bacteria that enter the gastrointestinal tract from the oral cavity via saliva may contribute to SSI prevention. Humans swallow 1.0–1.5 L of saliva per day, and patients with severe periodontitis swallow 1012–1013 oral bacteria per day [33]. During the perioperative period in pancreatic surgery, anti-acid agents, such as proton pump inhibitors, are often administered to prevent anastomotic ulcers. Fasting also decreases gastric juice secretion and weakens bactericidal effects. In patients with obstructive jaundice or postoperative external biliary drainage, the bactericidal effects of bile may be absent. In addition, oral bacteria exert cooperative protection via interspecies bacterial co-aggregation [34], and the elderly are particularly susceptible to the transfer of oral bacteria to the intestine [35]. Therefore, periodontal disease may disrupt the intestinal microbiome. Indeed, the gut microbiome of patients with periodontal disease has been reported to be less diverse than that of healthy individuals [36]. Low microbiome diversity may decrease mucosal barrier function. In animal models, oral administration of Porphyromonas gingivalis induced changes in the gut microbiota (dysbiosis), which resulted in decreased mucosal barrier function and BT [33]. In this study, perioperative oral care may have inhibited the transfer of pathogenic bacteria from the oral cavity to the intestinal tract, thereby reducing intestinal dysbiosis and BT from the intestinal tract, which in turn decreased the incidence of SSIs.
We previously reported that perioperative oral care is effective for preventing SSIs after colorectal cancer surgery [12]. In the present study, we observed similar results for PDAC in patients with colorectal cancer. We speculate that perioperative oral care contributes to the prevention of SSIs by reducing intestinal- and oral-derived BT. Preoperative remote site infections (urinary tract or respiratory infections) are risk factors for SSIs, and preoperative treatment is recommended [37]. Although the incidence of periodontal disease is higher than those of urinary tract and respiratory infections, the importance of preoperative remote infections in the oral cavity is commonly overlooked. Unlike antimicrobial prophylaxis, oral care does not promote opportunistic infection or antimicrobial resistance. Oral care can be easily integrated into perioperative multidisciplinary team medicine, such as the ERAS programme. We, therefore, believe that perioperative oral care is a safe and effective infection prevention strategy that should be implemented in future perioperative management.
This study has several limitations. First, this was a retrospective observational study. Information on the number of remaining teeth and the condition of periodontal tissues was unavailable; therefore, we were unable to investigate the associations between these factors and SSIs. Second, we were unable to examine the direct effects of oral care on intestinal microbiome, because we did not have the relevant data. Third, given that perioperative oral care has been covered by insurance in Japan since 2012, conducting a randomised controlled trial would be challenging. Therefore, multicentre retrospective cohort studies should be performed to investigate the relationship between oral care and SSIs.
In conclusion, our results suggest that perioperative oral care reduces the risk of developing SSIs after pancreatic cancer surgery. Our findings indicate that oral care is a safe perioperative infection prevention measure with no adverse events and should be incorporated in perioperative management. Future multicentre clinical trials are warranted to verify these results in a larger number of patients.