Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy

Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy Hiroya Iida, Masaki Kaibori, Hiromitsu Maehira, Haruki Mori, Nobuhito Nitta, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2685128/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jun, 2023 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose: Candida spp. cause opportunistic infections in conditions of immunodeficiency. Here, we investigated the relationship between colonization of the gastric juice by Candida spp. and surgical site infection (SSI) in hepatectomy. Methods: Consecutive hepatectomy cases between November 2019 and April 2021 were enrolled. Gastric juice samples (collected intraoperatively through a nasogastric tube) were cultured. We compared factors related to patient background, blood test findings, surgical findings, and postoperative complications between the Candida+ group (positive for colonization of the gastric juice by Candida spp.) and the Candida- group (negative). In addition, we identified the factors that contribute to SSI. Results: There were 29 and 71 patients in the Candida+ and Candida- groups, respectively. The Candida+ group was significantly older (average age: Candida+ 74 years vs. Candida- 69 years; p =0.02) and contained more patients who were negative for the hepatitis B and C virus ( Candida+ 93% vs. Candida- 69%; p =0.02). SSI was significantly more common in the Candida+ group ( Candida+ 31% vs. Candida- 9%; p =0.01). Postoperative bile leakage and colonization of the gastric juice by Candida spp. were independent predictors of SSI. Conclusion: Colonization of the gastric juice by Candida spp. is a risk factor for SSI after hepatectomy. Candida gastric juice hepatectomy microflora surgical site infection Figures Figure 1 Figure 2 Introduction Japan is currently facing a rapidly aging society and a steady increase in the number of elderly patients who require surgical treatments. Elderly patients often suffer from complications of cardiovascular diseases (such as cardiac infarction or angina pectoris) and cerebrovascular diseases (including cerebral infarction and hemorrhage). Their cardiopulmonary functions are generally weaker than those of younger people, and any complications induced by surgery can be aggravated. This is accompanied by an increase in medical expenses and a prolongation of the hospitalization period. Therefore, it is essential to predict and prevent postoperative complications. The number of elderly patients undergoing hepatectomy is increasing steadily. Several studies have reported on hepatectomy in the elderly[ 1 , 2 ], with many arguing that hepatectomy is as safe in elderly patients as in younger patients and that the risk of complications does not differ between older and younger patients. However, one study indicated that compared with younger patients, elderly patients exhibited a higher fatality rate from postoperative complications[ 3 ]. Various studies have investigated the prediction and prevention of postoperative complications. Preventive measures include the improvement of the intestinal flora by probiotics or synbiotics and the introduction of the enhanced recovery after surgery protocol[ 4 – 6 ]. The predictors for postoperative complications include the physical status classification system developed by the American Society of Anesthesiologists and the performance status score developed by the Eastern Cooperative Oncology Group[ 7 , 8 ]. However, these grading systems lack do not rely on objective factors. Sarcopenia, which indicates a decrease in muscle mass, is gradually being recognized as a predictor of postoperative complications[ 9 , 10 ]. In practice, the measurement of muscle mass is an inconvenient and complicated procedure, requiring the monitoring of body composition or a Dual-energy X-ray absorptiometry scan. Moreover, preoperative measurement of muscle mass using computed tomography is a substantial endeavor. In humans, the Candida genus is indigenous to the microflora of the oral cavity, gastrointestinal tract, and skin. It is usually an harmless fungus, but exhibits abnormal and opportunistic proliferation in conditions of immunodeficiency. Esophageal candidiasis is a relatively frequent disease that occurs in approximately 1% of patients who undergo upper gastrointestinal endoscopy. Its frequency is even higher in patients with cancer. Candida spp. can cause postoperative complications by colonizing the drainage site. This can lead to postoperative surgical site infection (SSI) or postoperative hemorrhage, as demonstrated in pancreatic fistulas that develop after pancreatic surgery[ 11 – 13 ]. In this study, we analyzed hepatectomy cases to confirm whether preoperative Candida colonization of the gastric juice is a valid predictor of SSI. Methods Of the 110 cases of hepatectomy performed consecutively at Shiga University of Medical Science Hospital from November 2019 to April 2021, 101 cases that did not match the exclusion criteria were included in our analysis. The exclusion criteria were as follows: patients undergoing simultaneous resection of other organs, receiving antifungal agents for fungal infection, after gastrectomy, or undergoing emergency surgery; and lack of written informed consent. Among patients who provided written informed consent and underwent surgery, 100 cases were analyzed. One case was excluded because a nasogastric tube could not be inserted due to a severe esophageal varix. The gastric juice was sampled via a nasogastric tube inserted under general anesthesia, and the samples were used for microbial culturing. A series of comparative analyses were performed in cases positive ( Candida + group, n = 29) and negative ( Candida - group, n = 71) for Candida spp. colonization of the gastric juice (Fig. 1 ). The primary endpoint was to analyze how preoperative colonization of the gastric juice with Candida spp. was associated with the rate of occurrence of SSI. The secondary endpoints were to identify the various factors contributing to SSI. Factors related to patient background included age, sex, body mass index (BMI), presence/absence of diabetes, administration of proton pump inhibitor (PPI) or H2 blockers, presence/absence of the hepatitis virus (B or C), history of smoking, and history of alcohol abuse. Surgical factors included primary disease, surgical method (anatomical vs. partial resection), initial vs. repeat hepatectomy, open vs. laparoscopic hepatectomy, intraoperative blood loss, and operative time. Blood samples were collected to measure the white blood cell (WBC) and platelet counts; the levels of hemoglobin (Hb), C-reactive protein (CRP), albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and β-D-glucan; prothrombin activity (PT); estimated glomerular filtration rate (eGFR); and indocyanine green retention rate at 15 minutes (ICGR15). Factors related to postoperative course included the rate of SSI occurrence, presence/absence of post-hepatectomy liver failure (PHLF), and presence/absence of postoperative bile leakage. Fluctuations in the levels of WBC and CRP on postoperative days (POD) 1, 3, 5, and 7 were also measured. Patients who used an insulin preparation or internal antidiabetic agent were defined as those with diabetes. Patients with a history of daily alcohol ingestion (≥ 20 g/day) were defined as those with a history of alcohol abuse. The history of smoking was determined using the Brinkman index (an indicator that predicts the impact of smoking on a human body). SSI was defined according to the guidelines of the Center for Disease Control and Prevention[ 14 ]. Bile leakage and PHLF were defined based on the guidelines of the International Study Group of Liver Surgery[ 15 , 16 ]. Collection of the gastric juice and detection of Candida spp. A nasogastric tube was inserted into patients under general anesthesia, and 5 ml of the gastric juice was collected from each patient. The mycological culture medium we used was CHROMagar Candida (Kanto Chemical Co., Inc., Japan, Tokyo), which has been shown to detect Candida spp. at a higher rate than conventional mediums[ 17 ]. Samples were incubated under aerobic conditions at 35°C and observed on days 1 and 2 to determine the results. Statistical analysis The age and BMI of the patients were presented as the mean ± standard deviation. Other continuous variables were expressed as the median and interquartile range. Between-group differences were analyzed with either the chi-squared test or Fisher's exact test for nominal variables; and either the Student's t -test or Mann–Whitney U test for continuous variables. For continuous variables, the cutoff values were selected using receiver operating characteristic (ROC) curve analysis. We chose cut-off values that were close to the thresholds for significant difference and were easy to apply clinically. Statistically significant variables in the univariate analysis were included in multivariate logistic regression analysis, and p -values < 0.05 were considered statistically significant in all analysis. All statistical analyses were performed in R statistical software version 4.0.2. (R Foundation for Statistical Computing, Vienna, Austria; https://cran.r-project.org/bin/macosx/ ). Results Candida spp. colonization of the gastric juice was observed in 29 patients. Specifically, Candida albicans was confirmed in 20 patients (68.9%), Candida glabrata in 6 (20.7%), and combined infection in 2 (10.4%). Patients were significantly older in the Candida + group (mean age: Candida + group, 74 years vs. Candida - group, 69 years; p = 0.024). The number of patients negative for the hepatitis B and C viruses was significantly higher in the Candida + group ( Candida + group, 93% vs. Candida- group, 69%; p = 0.022). Other factors related to patient background were not significantly different between groups. Among surgical factors, laparoscopic hepatectomies were significantly more common in the Candida - group ( Candida + group, 45% vs. Candida- group, 69%; p = 0.04). However, operative time, volume of blood loss, primary disease, surgical method, and the rate of repeat hepatectomy were not significantly different between groups. The level of total bilirubin was significantly lower value in the Candida + group ( Candida + group, 0.58 mg/dL vs. Candida - group, 0.78 mg/dL; p = 0.016), whereas the platelet count was significantly higher ( Candida + group, 212,000 /µL vs. Candida - group, 153,000/µL; p = 0.007). The other factors measured in blood tests were not significantly different between groups (Table 1 ). Table 1 Comparison of background factors between the Candida + and Candida - groups. Candida - group Candida + group p -value (n = 71) (n = 29) Age (years) 69.1 ± 10.1 74.2 ± 9.8 0.024 Sex (%) Men 54 (76.1) 19 (65.5) 0.325 Women 17 (23.9) 10 (34.5) BMI (kg/m 2 ) 23.9 ± 3.5 23.4 ± 3.5 0.524 Etiology (%) HBV 6 (8.5) 1 (3.4) 0.029 HCV 16 (22.5) 1 (3.4) NBNC 49 (69.0) 27 (93.1) DM (%) 22 (31.0) 8 (27.6) 0.813 Alcohol abuse (%) 20 (28.2) 7 (24.1) 0.806 Smoking history (*Brinkman index) 400 [0, 800] 400 [0, 600] 0.406 Medication of PPI or H2 blocker (%) 30 (42.3) 13 (44.8) 0.827 Primary disease (%) HCC 40 (56.3) 13 (44.8) 0.466 ICC 3 (4.2) 1 (3.4) Meta 24 (33.8) 11 (37.9) Others 4 (5.6) 4 (13.8) WBC (x1000/µL) 4.9 [3.6, 6.0] 5.0 [4.3, 6.1] 0.39 PLT (x1000/µL) 153 [112, 212] 212 [141, 257] 0.007 ALB (g/dL) 3.9 [3.6, 4.1] 3.8 [3.4, 4.1] 0.147 AST (IU/L) 28 [20, 43] 25 [20, 33] 0.257 ALT (IU/L) 23 [17, 39] 20 [15, 33] 0.185 T-BIL (mg/dL) 0.7 [0.5, 1.1] 0.5 [0.5, 0.7] 0.016 PT (%) 94 [86, 104] 96 [85, 104] 0.96 eGFR (mL/min/1.73 m 2 ) 68.3 [54.8, 79.7] 68.4 [58.5, 73.9] 0.936 CRP (mg/dL) 0.12 [0.05, 0.20] 0.15 [0.04, 0.26] 0.361 ICGR 15 (%) 12.8 [7.3, 18.6] 9.9 [7.2, 13.9] 0.188 β-D-glucan (pg/mL) 3.5 [2.7, 6.7] 3.6 [2.7, 6.4] 0.677 Laparoscopic hepatectomy (%) 49 (69.0) 13 (44.8) 0.04 Anatomical resection (%) 30 (42.3) 13 (44.8) 0.827 Repeat hepatectomy (%) 25 (35.2) 8 (27.6) 0.494 Operative time (min) 268 [204, 342] 266 [227, 376] 0.358 Blood loss (mL) 220 [35, 640] 250 [80, 556] 0.672 Abbreviations: BMI, body mass index; DM, diabetes mellitus; PPI, proton pump inhibitor; WBC, white blood cell count; PLT, platelet count; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; T-BIL, total bilirubin; PT, prothrombin activity; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; ICGR15, indocyanine green retention rate at 15 minutes; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, negative for the hepatitis B and C virus; HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; Meta, liver metastasis *Brinkman index is calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking. Age and BMI are expressed as the mean ± standard deviation. Other data are expressed as the median [25th percentile, 75th percentile]. The rate of SSI occurrence was significantly ( p = 0.01) higher in the Candida + group (31.0%, nine patients) than in the Candida - group (8.5%, six patients). Other factors related to postoperative complications, including PHLF and postoperative bile leakage, were similar between groups (Table 2 ). Table 2 Comparison of factors related to postoperative course. Candida - group Candida + group p -value (n = 71) (n = 29) SSI (%) 6 (8.5) 9 (31.0) 0.01 PHLF (%) A 4 (5.6) 1 (3.4) > 0.999 B 6 (8.5) 2 (6.9) C 0 0 Bile leakage (%) 9 (12.7) 4 (13.8) > 0.999 Postoperative hospital stays (days) 10 [ 8 , 16 ] 14 [ 9 , 22 ] 0.077 Abbreviations: SSI, surgical site infection; PHLF, post-hepatectomy liver failure Postoperative hospital stay is expressed as the median [25th percentile, 75th percentile]. The results of univariate analysis indicated significant between-group differences in seven items: colonization of the gastric juice by Candida spp., anatomical resection, open hepatectomy, postoperative bile leakage, β-D-glucan ≥ 3.5 pg/mL, operative time ≥ 360 min, and blood loss volume ≥ 1000 mL. Multivariate analysis with these factors identified postoperative bile leakage (odds ratio 8.89, 95% CI 1.54–51.5) and colonization of the gastric juice by Candida sp. (odds ratio 8.17, 95% CI 1.65–40.5) as independent predictors (Table 3 ). Table 3 Univariate and multivariate analyses to identify factors predictive of surgical site infection after hepatectomy. Univariate analysis Multivariate analysis Odds ratio (95% CI) p -value Odds ratio p -value Age > 75 years 2.90 (0.94–8.93) 0.064 Male patients 0.70 (0.22–2.27) 0.55 BMI > 25 kg/m 2 0.31 (0.07–1.48) 0.14 HBV or HCV patients 1.18 (0.34–4.12) 0.79 Presence of DM 0.54 (0.14–2.06) 0.36 Alcohol abuse 0.64 (0.17–2.45) 0.51 Smoking history (*Brinkman index > 400) 0.67 (0.22–2.03) 0.48 Medication history of PPI or H2 blocker 1.19 (0.40–3.58) 0.76 HCC patients 0.74 (0.25–2.23) 0.6 WBC > 5000 x1000/µL 1.17 (0.39–3.51) 0.78 PLT < 100 x1000/µL 0.44 (0.05–3.62) 0.44 ALB 30 IU/L 2.36 (0.77–7.25) 0.13 ALT > 30 IU/L 1.22 (0.40–3.76) 0.73 BIL > 1.0 mg/dL 0.64 (0.17–2.45) 0.51 PT < 75% 3.07 (0.81–11.70) 0.1 eGFR 0.3 mg/dL 2.45 (0.66–9.05) 0.18 ICGR15 > 10% 1.33 (0.44–4.08) 0.61 β-D-Glucan > 3.5 pg/mL 3.74 (1.10–12.70) 0.034 1.58 (0.28–8.71) 0.6 Open hepatectomy 9.08 (2.36–34.90) 0.0013 2.62 (0.43–16.20) 0.3 Anatomical resection 4.55 (1.34–15.50) 0.015 2.38 (0.50–11.40) 0.28 Repeat hepatectomy 0.46 (0.12–1.75) 0.25 Operative time > 360 minutes 4.25 (1.36–13.30) 0.013 2.61 (0.61–11.20) 0.2 Blood loss > 1000 mL 3.75 (1.06–13.20) 0.04 1.99 (0.34–11.60) 0.44 PHLF grade A or B 1.03 (0.21–5.22) 0.97 Postoperative bile leakage 11.50 (3.11–42.70) 0.00026 8.89 (1.54–51.50) 0.015 Colonization of the gastric juice by Candida spp. 4.87 (1.55–15.40) 0.0068 8.17 (1.65–40.50) 0.01 Abbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; DM, diabetes mellitus; PPI, proton pump inhibitor; HCC, hepatocellular carcinoma; WBC, white blood cell count; PLT, platelet count; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; T-BIL, total bilirubin; PT, prothrombin activity; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; ICGR15, indocyanine green retention rate at 15 minutes *The Brinkman index is calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking. Figure 2 shows the fluctuations in postoperative WBC and CRP level. There were no significant differences in WBC before surgery or on POD 1, 3, 5, and 7. There were no significant differences in CRP levels before surgery or on POD 1, 3, and 5. However, the Candida + group exhibited a significantly higher CRP level on POD 7 ( Candida + group, 5.76 mg/dL vs. Candida - group, 3.84 mg/dL; p = 0.024). Discussion In this study, we used hepatectomy cases to investigate the relationship between preoperative colonization of the gastric juice by Candida spp. and the rate of SSI occurrence. Our results revealed that preoperative colonization of the gastric juice by Candida spp. was an independent predictor of postoperative SSI. Candida spp. are frequently detected in samples collected from healthy individuals (oropharynx, 30%; stomach, 47%; jejunum, 54%; ileum, 55%; and fecal, 65%). Although it is a commensal fungus that is usually harmless to the human body, conditions of immunodeficiency (e.g., following infection with the human immunodeficiency virus (HIV), long-term steroid use, and chemotherapy) can lead to opportunistic infections by Candida spp. Some of these infections can cause severe deterioration in patient health. The above findings suggest a close association between immunity and Candida spp. infections. Several studies using the scoring of immunological vigor[ 18 , 19 ] have indicated that immunity can be degraded following an increase in the intraoral abundance of Candida spp. The abundance of Candida spp. is negatively correlated with the number of T-cells, native T-cells, and CD8 + CD28 + T-cells, as well as with the ratio of native T-cells to memory T-cells[ 20 ]. The presence of Candida spp. in the oral cavity may also be a biomarker of HIV infection-induced immunodeficiency. [ 21 ] As shown above, immunity is associated with the presence of Candida spp. Accordingly, postoperative infectious complications may also be associated with Candida spp. Candida spp. have been shown to infect the drainage sites of patients who underwent pancreaticoduodenectomy; as such, this is considered a risk factor for hemorrhagic complications associated with postoperative pancreatic fistula[ 12 ]. Several studies have also demonstrated the presence of Candida spp. in the bile of patients who underwent pancreatoduodenectomy, suggesting that this is a significant risk factor of postoperative SSI[ 11 , 13 ]. A study on high-level hepato-biliary-pancreatic surgery demonstrated a relationship between the colonization of the gastric juice by Candida spp. and postoperative SSI[ 22 ]. In that study, colonization of the gastric juice by Candida spp. was detected in 21/66 patients (31.8%). Postoperative SSI occurred in 57.1% of the patients positive for Candida colonization of the gastric juice and in 17.8% of patients negative for Candida spp. colonization ( p = 0.001). In our study, 29/100 patients (29.0%) were positive in the Candida + group, which is consistent with the result of the previous study. In addition, 31.0% and 8.5% of patients in the Candida + and Candida - groups developed SSI. Previous studies examined various surgeries, including hepatectomy, pancreatectomy, bile duct resection, and others. The novelty of our study lies in the fact that we focused specifically on hepatectomy cases, and our findings indicate a strong correlation between the presence of Candida spp. in the gastric juice and postoperative SSI in hepatectomy cases. The mechanism through which colonization of the intragastric juice by Candida spp. influences the development of SSI remains unknown. Candida spp. are known to cause damage to mucosal epithelial cells, thus facilitating infections by other microbes[ 23 ]. They are also considered to directly stimulate the propagation of pathogens such as Staphylococcus aureus , Serratia marcescens , and Streptococcus faecalis [ 24 ]. We did not detect Candida spp. in any drainage fluids in this study (data not shown). This suggested that Candida spp. in the gastric juice were not directly responsible for SSI, although they may have stimulated other microbes to cause SSI. The propagation of Candida spp. is known to cause disturbances in the intestinal flora[ 25 , 26 ], which is associated with SSI. Thus, Candida -related disturbances in intestinal flora may be one of the mechanisms underlying SSI[ 4 – 6 ]. Several studies have reported that reduced secretion of gastric acid can lead to the propagation of Candida spp. or disturbances in intestinal flora. Thus, patients with a history of gastrectomy may exhibit reduced gastric acid secretion and were excluded from our study[ 27 – 30 ]. Treatment with PPI or H2 blockers can reduce gastric acid secretion. In this study, the proportion of patients who received PPI or H2 blockers was similar between the Candida + and Candida - groups. Our study has some limitations. First, we measured Candida spp. in the gastric juice, and not in the intraoral cavity (which is much easier to sample). Intraoral conditions can change drastically due to eating, mouth-washing, or teeth-brushing; therefore, measurement under constant conditions is challenging. Moreover, Candida spp. were detected more frequently in the gastric juice (29/100 cases) than in the oral cavity (9/100 cases). Due to the above reasons, we focused on Candida spp. colonization in the intra-gastric juice. Second, the presence of Candida spp. was measured by collecting the gastric juice via a nasogastric tube inserted just after general anesthesia. Although the procedure was patient-friendly, the gastric juice samples could only be collected immediately before surgery. This made is impossible to perform any preoperative interventions. Since the presence of Candida spp. in the gastric juice contributes to the development of SSI, it is necessary to investigate whether SSI can be reduced through the preoperative use of antimycotic agents. However, the protocol used in this study did not allow the pre-administration of antimycotic agents. A prospective study is needed in which the gastric juice is sampled in advance and antimycotic agents are administered to patients who are positive for the presence of Candida spp. Finally, this was a single-center study with a limited sample size. A multicenter study with a larger number of cases should be conducted in the future. In conclusion, the present study demonstrated that the colonization of the gastric juice by Candida spp. before hepatectomy may be a predictor of postoperative SSI. Declarations The authors have no conflicts of interest to declare. Ethical declaration This prospective observational study conformed to the Clinical Research Guidelines and was approved by the ethics committee of our institution (institutional approval number: R2019-138). Written informed consent was obtained from all patients. In addition, this study was registered with UMIN-CTR (identifying number: UMIN 000048860). Acknowledgments Not applicable. Funding/Financial Support No funding was received for this study. Author contributions HI and MK designed the research and analyzed the patient data. HI, HM, HM, NN, TM, KT, SK, TM, and MT collected the data. HI drafted the manuscript. All authors have read and approved the final version of the manuscript. Availability of protocol, data, and material The protocol or datasets used during the current study are available from the corresponding author on reasonable request. References Kaibori M, Matsui K, Ishizaki M, Saito T, Kitade H, Matsui Y, Kwon AH (2009) Hepatic resection for hepatocellular carcinoma in the elderly. J Surg Oncol 99(3):154-160. https://doi.org/10.1002/jso.21221 Iida H, Kaibori M, Matsui K, Ishizaki M, Kon M (2017) Assessing the feasibility of clinicopathological features of hepatic resection for hepatocellular carcinoma in patients over 80 years of age. Mol Clin Oncol 6(1):29-38. https://doi.org/10.3892/mco.2016.1079 Mirici-Cappa F, Gramenzi A, Santi V, Zambruni A, Di Micoli A, Frigerio M, Maraldi F, Di Nolfo MA, Del Poggio P, Benvegnù L, Rapaccini G, Farinati F, Zoli M, Borzio F, Giannini EG, Caturelli E, Bernardi M, Trevisani F (2010) Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience. Gut 59(3):387-396. https://doi.org/10.1136/gut.2009.194217 Sugawara G, Nagino M, Nishio H, Ebata T, Takagi K, Asahara T, Nomoto K, Nimura Y (2006) Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Ann Surg 244(5):706-714. https://doi.org/10.1097/01.sla.0000219039.20924.88 Usami M, Miyoshi M, Kanbara Y, Aoyama M, Sakaki H, Shuno K, Hirata K, Takahashi M, Ueno K, Tabata S, Asahara T, Nomoto K (2011) Effects of perioperative synbiotic treatment on infectious complications, intestinal integrity, and fecal flora and organic acids in hepatic surgery with or without cirrhosis. JPEN J Parenter Enteral Nutr 35(3):317-328. https://doi.org/10.1177/0148607110379813 Iida H, Sasaki M, Maehira H, Mori H, Yasukawa D, Takebayashi K, Kurihara M, Bamba S, Tani M (2020) The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection. J Clin Biochem Nutr 66(1):67-73. https://doi.org/10.3164/jcbn.19-46 Owens WD, Felts JA, Spitznagel EL, Jr. (1978) ASA physical status classifications: a study of consistency of ratings. Anesthesiology 49(4):239-243. https://doi.org/10.1097/00000542-197810000-00003 Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649-655 Nishigori T, Tsunoda S, Okabe H, Tanaka E, Hisamori S, Hosogi H, Shinohara H, Sakai Y (2016) Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. Annals of Surgical Oncology 23:524-531. https://doi.org/10.1245/s10434-016-5385-y Namm JP, Thakrar KH, Wang CH, Stocker SJ, Sur MD, Berlin J, Dale W, Talamonti MS, Roggin KK (2017) A semi-automated assessment of sarcopenia using psoas area and density predicts outcomes after pancreaticoduodenectomy for pancreatic malignancy. Journal of Gastrointestinal Oncology 8(6):936-944. https://doi.org/10.21037/jgo.2017.08.09 Kato H, Iizawa Y, Kishiwada M, Usui M, Nakamura A, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Mizuno S, Sakurai H, Isaji S (2016) Negative Impact of Biliary Candidiasis on Early and Late Postoperative Complications After Pancreatoduodenectomy Usefulness of the CHROMagar Candida Plate for Identification. Pancreas 45(9):e45-47. https://doi.org/10.1097/mpa.0000000000000682 Sato A, Masui T, Nakano K, Sankoda N, Anazawa T, Takaori K, Kawaguchi Y, Uemoto S (2017) Abdominal contamination with Candida albicans after pancreaticoduodenectomy is related to hemorrhage associated with pancreatic fistulas. Pancreatology 17(3):484-489. https://doi.org/10.1016/j.pan.2017.03.007 Kato H, Iizawa Y, Nakamura K, Gyoten K, Hayasaki A, Fujii T, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Kishiwada M, Mizuo S, Usui M, Sakurai H, Isaji S (2018) The Critical Role of Biliary Candidiasis in Development of Surgical Site Infections after Pancreatoduodenectomy: Results of Prospective Study Using a Selective Culture Medium for Candida Species. Biomed Res Int 2018:5939724. https://doi.org/10.1155/2018/5939724 Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, Dellinger EP, Itani KMF, Berbari EF, Segreti J, Parvizi J, Blanchard J, Allen G, Kluytmans J, Donlan R, Schecter WP (2017) Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg 152(8):784-791. https://doi.org/10.1001/jamasurg.2017.0904 Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Büchler MW, Weitz J (2011) Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 149(5):713-724. https://doi.org/10.1016/j.surg.2010.10.001 Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras J, DeMatteo RP, Büchler MW, Weitz J (2011) Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery 149(5):680-688. https://doi.org/10.1016/j.surg.2010.12.002 Baumgartner C, Freydiere AM, Gille Y (1996) Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates. J Clin Microbiol 34(2):454-456. https://doi.org/10.1128/jcm.34.2.454-456.1996 Hirokawa K, Utsuyama M, Ishikawa T, Kikuchi Y, Kitagawa M, Fujii Y, Nariuchi H, Uetake H, Sugihara K (2009) Decline of T cell-related immune functions in cancer patients and an attempt to restore them through infusion of activated autologous T cells. Mech Ageing Dev 130(1-2):86-91. https://doi.org/10.1016/j.mad.2008.05.001 Hirokawa K, Utsuyama M, Hayashi Y, Kitagawa M, Makinodan T, Fulop T (2013) Slower immune system aging in women versus men in the Japanese population. Immun Ageing 10(1):19. https://doi.org/10.1186/1742-4933-10-19 Hayashi K, Tooyama H, Tanaka H, Aizawa H, Shimane T, Kurashina K, Yamada SI, Kurita H (2017) Relationship between the quantity of oral Candida and immunological vigor. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29(1):65-70. https://doi.org/10.1016/j.ajoms.2016.09.011 Korting HC, Ollert M, Georgii A, Fröschl M (1988) In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. J Clin Microbiol 26(12):2626-2631. https://doi.org/10.1128/jcm.26.12.2626-2631.1988 Gyoten K, Kato H, Hayasaki A, Fujii T, Iizawa Y, Murata Y, Tanemura A, Kuriyama N, Kishiwada M, Mizuno S, Usui M, Sakurai H, Isaji S (2021) Association between gastric Candida colonization and surgical site infections after high-level hepatobiliary pancreatic surgeries: the results of prospective observational study. Langenbecks Arch Surg 406(1):109-119. https://doi.org/10.1007/s00423-020-02006-7 Shirtliff ME, Peters BM, Jabra-Rizk MA (2009) Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol Lett 299(1):1-8. https://doi.org/10.1111/j.1574-6968.2009.01668.x Carlson E (1983) Enhancement by Candida albicans of Staphylococcus aureus, Serratia marcescens, and Streptococcus faecalis in the establishment of infection in mice. Infect Immun 39(1):193-197. https://doi.org/10.1128/iai.39.1.193-197.1983 Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, Cosnes J, Seksik P, Langella P, Skurnik D, Richard ML, Beaugerie L (2017) Fungal microbiota dysbiosis in IBD. Gut 66(6):1039-1048. https://doi.org/10.1136/gutjnl-2015-310746 Yang AM, Inamine T, Hochrath K, Chen P, Wang L, Llorente C, Bluemel S, Hartmann P, Xu J, Koyama Y, Kisseleva T, Torralba MG, Moncera K, Beeri K, Chen CS, Freese K, Hellerbrand C, Lee SML, Hoffman HM, Mehal WZ, Garcia-Tsao G, Mutlu EA, Keshavarzian A, Brown GD, Ho SB, Bataller R, Stärkel P, Fouts DE, Schnabl B (2017) Intestinal fungi contribute to development of alcoholic liver disease. Journal of Clinical Investigation 127(7):2829-2841. https://doi.org/10.1172/JCI90562 Shindo K, Fukumura M (1995) Effect of H2-receptor antagonists on bile acid metabolism. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 43(2):170-177 Shindo K, Machida M, Fukumura M, Koide K, Yamazaki R (1998) Omeprazole induces altered bile acid metabolism. Gut 42(2):266-271. https://doi.org/10.1136/gut.42.2.266 Brzozowski T, Zwolinska-Wcislo M, Konturek PC, Kwiecien S, Drozdowicz D, Konturek SJ, Stachura J, Budak A, Bogdal J, Pawlik WW, Hahn EG (2005) Influence of gastric colonization with Candida albicans on ulcer healing in rats: Effect of ranitidine, aspirin and probiotic therapy. Scandinavian Journal of Gastroenterology 40(3):286-296. https://doi.org/10.1080/00365520510011524 Martinsen TC, Bergh K, Waldum HL (2005) Gastric juice: A barrier against infectious diseases. Basic and Clinical Pharmacology and Toxicology 96(2):94-102. https://doi.org/10.1111/j.1742-7843.2005.pto960202.x Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Jun, 2023 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editorial decision: Major revision 15 Apr, 2023 Reviews received at journal 15 Apr, 2023 Reviewers agreed at journal 05 Apr, 2023 Reviews received at journal 31 Mar, 2023 Reviewers agreed at journal 30 Mar, 2023 Reviewers invited by journal 30 Mar, 2023 Editor assigned by journal 15 Mar, 2023 Submission checks completed at journal 14 Mar, 2023 First submitted to journal 12 Mar, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2685128","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":183543168,"identity":"56d87031-93e4-4a88-a466-3e8789f507f0","order_by":0,"name":"Hiroya Iida","email":"data:image/png;base64,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","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hiroya","middleName":"","lastName":"Iida","suffix":""},{"id":183543169,"identity":"63bbb055-c8aa-4c00-8958-4ba8fc1698fb","order_by":1,"name":"Masaki Kaibori","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masaki","middleName":"","lastName":"Kaibori","suffix":""},{"id":183543170,"identity":"c129d1e3-27e5-4e13-b346-33406d6a5d26","order_by":2,"name":"Hiromitsu Maehira","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiromitsu","middleName":"","lastName":"Maehira","suffix":""},{"id":183543171,"identity":"26e4bc0f-5b85-4429-bd5d-d8909c5bde10","order_by":3,"name":"Haruki Mori","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haruki","middleName":"","lastName":"Mori","suffix":""},{"id":183543172,"identity":"3ded3b9b-84eb-47f3-b3a8-772b11228e14","order_by":4,"name":"Nobuhito Nitta","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nobuhito","middleName":"","lastName":"Nitta","suffix":""},{"id":183543173,"identity":"97a3dba2-ff41-4405-a7f4-a20f3d7301a5","order_by":5,"name":"Takeru Maekawa","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Takeru","middleName":"","lastName":"Maekawa","suffix":""},{"id":183543174,"identity":"8bb93f8f-d45f-42b9-803f-4973e688e62b","order_by":6,"name":"Katsushi Takebayashi","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Katsushi","middleName":"","lastName":"Takebayashi","suffix":""},{"id":183543175,"identity":"3766767f-98ff-4f3e-bd85-22f526cba3c5","order_by":7,"name":"Sachiko Kaida","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sachiko","middleName":"","lastName":"Kaida","suffix":""},{"id":183543177,"identity":"a5b26187-6654-4945-a0e2-23c020be3211","order_by":8,"name":"Toru Miyake","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Toru","middleName":"","lastName":"Miyake","suffix":""},{"id":183543179,"identity":"0670eccd-da6d-4188-9932-939d1977c7f1","order_by":9,"name":"Masaji Tani","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masaji","middleName":"","lastName":"Tani","suffix":""}],"badges":[],"createdAt":"2023-03-13 03:14:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2685128/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2685128/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00423-023-02978-2","type":"published","date":"2023-06-20T21:16:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":34361615,"identity":"b3fca9dd-25a1-41a7-96a2-a9b97dad2192","added_by":"auto","created_at":"2023-03-16 14:42:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":85424,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart detailing patient enrolment, inclusion, and exclusion.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 110 patients who received hepatectomy consecutively from November 2019 to April 2021, written informed consent is obtained from 101 patients. Three patients are excluded after gastrectomy, two after esophagectomy, and four with accompanying biliary tract reconstruction. One patient is excluded because a nasogastric tube could not be inserted during surgery. A total of 100 patients are divided into two groups based on colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp.: positive (\u003cem\u003eCandida\u003c/em\u003e+ group, n=29) and negative (\u003cem\u003eCandida\u003c/em\u003e- group, n=71).\u003c/p\u003e","description":"","filename":"OnlinecandidaFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2685128/v1/ceb5328afc86ccf0dffb4437.png"},{"id":34361604,"identity":"4e5680c4-5a02-4dc7-94cd-f105c2c8c2b9","added_by":"auto","created_at":"2023-03-16 14:42:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":97828,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in markers of postoperative inflammation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no significant differences in white blood cell (WBC) count before surgery and on post-operative days (POD) 1, 3, 5, and 7. The levels of C-reactive protein (CRP) are not significantly different before surgery and on POD 1, 3, and 5. However, CRP levels are significantly higher on POD 7.\u003c/p\u003e","description":"","filename":"OnlinecandidaFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2685128/v1/d2698abe32ca4e1dec38e365.png"},{"id":44733784,"identity":"1a2a5a03-c0d0-483f-adaa-407e4634dea2","added_by":"auto","created_at":"2023-10-16 22:10:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":583267,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2685128/v1/3563fa6c-5021-4367-8f79-f84a27e94742.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eJapan is currently facing a rapidly aging society and a steady increase in the number of elderly patients who require surgical treatments. Elderly patients often suffer from complications of cardiovascular diseases (such as cardiac infarction or angina pectoris) and cerebrovascular diseases (including cerebral infarction and hemorrhage). Their cardiopulmonary functions are generally weaker than those of younger people, and any complications induced by surgery can be aggravated. This is accompanied by an increase in medical expenses and a prolongation of the hospitalization period. Therefore, it is essential to predict and prevent postoperative complications. The number of elderly patients undergoing hepatectomy is increasing steadily. Several studies have reported on hepatectomy in the elderly[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with many arguing that hepatectomy is as safe in elderly patients as in younger patients and that the risk of complications does not differ between older and younger patients. However, one study indicated that compared with younger patients, elderly patients exhibited a higher fatality rate from postoperative complications[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVarious studies have investigated the prediction and prevention of postoperative complications. Preventive measures include the improvement of the intestinal flora by probiotics or synbiotics and the introduction of the enhanced recovery after surgery protocol[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The predictors for postoperative complications include the physical status classification system developed by the American Society of Anesthesiologists and the performance status score developed by the Eastern Cooperative Oncology Group[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, these grading systems lack do not rely on objective factors. Sarcopenia, which indicates a decrease in muscle mass, is gradually being recognized as a predictor of postoperative complications[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In practice, the measurement of muscle mass is an inconvenient and complicated procedure, requiring the monitoring of body composition or a Dual-energy X-ray absorptiometry scan. Moreover, preoperative measurement of muscle mass using computed tomography is a substantial endeavor.\u003c/p\u003e \u003cp\u003eIn humans, the \u003cem\u003eCandida\u003c/em\u003e genus is indigenous to the microflora of the oral cavity, gastrointestinal tract, and skin. It is usually an harmless fungus, but exhibits abnormal and opportunistic proliferation in conditions of immunodeficiency. Esophageal candidiasis is a relatively frequent disease that occurs in approximately 1% of patients who undergo upper gastrointestinal endoscopy. Its frequency is even higher in patients with cancer. \u003cem\u003eCandida\u003c/em\u003e spp. can cause postoperative complications by colonizing the drainage site. This can lead to postoperative surgical site infection (SSI) or postoperative hemorrhage, as demonstrated in pancreatic fistulas that develop after pancreatic surgery[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this study, we analyzed hepatectomy cases to confirm whether preoperative \u003cem\u003eCandida\u003c/em\u003e colonization of the gastric juice is a valid predictor of SSI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eOf the 110 cases of hepatectomy performed consecutively at Shiga University of Medical Science Hospital from November 2019 to April 2021, 101 cases that did not match the exclusion criteria were included in our analysis. The exclusion criteria were as follows: patients undergoing simultaneous resection of other organs, receiving antifungal agents for fungal infection, after gastrectomy, or undergoing emergency surgery; and lack of written informed consent. Among patients who provided written informed consent and underwent surgery, 100 cases were analyzed. One case was excluded because a nasogastric tube could not be inserted due to a severe esophageal varix. The gastric juice was sampled via a nasogastric tube inserted under general anesthesia, and the samples were used for microbial culturing. A series of comparative analyses were performed in cases positive (\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, n\u0026thinsp;=\u0026thinsp;29) and negative (\u003cem\u003eCandida\u003c/em\u003e- group, n\u0026thinsp;=\u0026thinsp;71) for \u003cem\u003eCandida\u003c/em\u003e spp. colonization of the gastric juice (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe primary endpoint was to analyze how preoperative colonization of the gastric juice with \u003cem\u003eCandida\u003c/em\u003e spp. was associated with the rate of occurrence of SSI. The secondary endpoints were to identify the various factors contributing to SSI. Factors related to patient background included age, sex, body mass index (BMI), presence/absence of diabetes, administration of proton pump inhibitor (PPI) or H2 blockers, presence/absence of the hepatitis virus (B or C), history of smoking, and history of alcohol abuse. Surgical factors included primary disease, surgical method (anatomical vs. partial resection), initial vs. repeat hepatectomy, open vs. laparoscopic hepatectomy, intraoperative blood loss, and operative time. Blood samples were collected to measure the white blood cell (WBC) and platelet counts; the levels of hemoglobin (Hb), C-reactive protein (CRP), albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and β-D-glucan; prothrombin activity (PT); estimated glomerular filtration rate (eGFR); and indocyanine green retention rate at 15 minutes (ICGR15). Factors related to postoperative course included the rate of SSI occurrence, presence/absence of post-hepatectomy liver failure (PHLF), and presence/absence of postoperative bile leakage. Fluctuations in the levels of WBC and CRP on postoperative days (POD) 1, 3, 5, and 7 were also measured. Patients who used an insulin preparation or internal antidiabetic agent were defined as those with diabetes. Patients with a history of daily alcohol ingestion (\u0026ge;\u0026thinsp;20 g/day) were defined as those with a history of alcohol abuse. The history of smoking was determined using the Brinkman index (an indicator that predicts the impact of smoking on a human body). SSI was defined according to the guidelines of the Center for Disease Control and Prevention[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Bile leakage and PHLF were defined based on the guidelines of the International Study Group of Liver Surgery[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eCollection of the gastric juice and detection of\u003c/b\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eCandida\u003c/span\u003e \u003cb\u003espp.\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA nasogastric tube was inserted into patients under general anesthesia, and 5 ml of the gastric juice was collected from each patient. The mycological culture medium we used was CHROMagar Candida (Kanto Chemical Co., Inc., Japan, Tokyo), which has been shown to detect \u003cem\u003eCandida\u003c/em\u003e spp. at a higher rate than conventional mediums[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Samples were incubated under aerobic conditions at 35\u0026deg;C and observed on days 1 and 2 to determine the results.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe age and BMI of the patients were presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Other continuous variables were expressed as the median and interquartile range. Between-group differences were analyzed with either the chi-squared test or Fisher's exact test for nominal variables; and either the Student's \u003cem\u003et\u003c/em\u003e-test or Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test for continuous variables. For continuous variables, the cutoff values were selected using receiver operating characteristic (ROC) curve analysis. We chose cut-off values that were close to the thresholds for significant difference and were easy to apply clinically. Statistically significant variables in the univariate analysis were included in multivariate logistic regression analysis, and \u003cem\u003ep\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant in all analysis. All statistical analyses were performed in R statistical software version 4.0.2. (R Foundation for Statistical Computing, Vienna, Austria; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cran.r-project.org/bin/macosx/\u003c/span\u003e\u003cspan address=\"https://cran.r-project.org/bin/macosx/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cem\u003eCandida\u003c/em\u003e spp. colonization of the gastric juice was observed in 29 patients. Specifically, \u003cem\u003eCandida albicans\u003c/em\u003e was confirmed in 20 patients (68.9%), \u003cem\u003eCandida glabrata\u003c/em\u003e in 6 (20.7%), and combined infection in 2 (10.4%). Patients were significantly older in the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group (mean age: \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, 74 years vs. \u003cem\u003eCandida\u003c/em\u003e- group, 69 years; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024). The number of patients negative for the hepatitis B and C viruses was significantly higher in the \u003cem\u003eCandida\u0026thinsp;+\u0026thinsp;group\u003c/em\u003e (\u003cem\u003eCandida\u0026thinsp;+\u003c/em\u003e\u0026thinsp;group, 93% vs. \u003cem\u003eCandida-\u003c/em\u003e group, 69%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022). Other factors related to patient background were not significantly different between groups.\u003c/p\u003e \u003cp\u003eAmong surgical factors, laparoscopic hepatectomies were significantly more common in the \u003cem\u003eCandida\u003c/em\u003e- group (\u003cem\u003eCandida\u0026thinsp;+\u003c/em\u003e\u0026thinsp;group, 45% vs. \u003cem\u003eCandida-\u003c/em\u003e group, 69%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). However, operative time, volume of blood loss, primary disease, surgical method, and the rate of repeat hepatectomy were not significantly different between groups. The level of total bilirubin was significantly lower value in the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group (\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, 0.58 mg/dL vs. \u003cem\u003eCandida\u003c/em\u003e- group, 0.78 mg/dL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), whereas the platelet count was significantly higher (\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, 212,000 /\u0026micro;L vs. \u003cem\u003eCandida\u003c/em\u003e- group, 153,000/\u0026micro;L; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). The other factors measured in blood tests were not significantly different between groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of background factors between the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;and \u003cem\u003eCandida\u003c/em\u003e- groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e- group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (76.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWomen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (34.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEtiology (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHBV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNBNC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (69.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (93.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol abuse (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history (*Brinkman index)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e400 [0, 800]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e400 [0, 600]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication of PPI or H2 blocker (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eICC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (x1000/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.9 [3.6, 6.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.0 [4.3, 6.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT (x1000/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153 [112, 212]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e212 [141, 257]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9 [3.6, 4.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.8 [3.4, 4.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 [20, 43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 [20, 33]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 [17, 39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 [15, 33]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-BIL (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7 [0.5, 1.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5 [0.5, 0.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 [86, 104]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 [85, 104]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.3 [54.8, 79.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.4 [58.5, 73.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12 [0.05, 0.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15 [0.04, 0.26]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICGR 15 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.8 [7.3, 18.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.9 [7.2, 13.9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-D-glucan (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 [2.7, 6.7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6 [2.7, 6.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaparoscopic hepatectomy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (69.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnatomical resection (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepeat hepatectomy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268 [204, 342]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e266 [227, 376]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220 [35, 640]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e250 [80, 556]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.672\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: BMI, body mass index; DM, diabetes mellitus; PPI, proton pump inhibitor; WBC, white blood cell count; PLT, platelet count; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; T-BIL, total bilirubin; PT, prothrombin activity; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; ICGR15, indocyanine green retention rate at 15 minutes; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, negative for the hepatitis B and C virus; HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; Meta, liver metastasis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Brinkman index is calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAge and BMI are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Other data are expressed as the median [25th percentile, 75th percentile].\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe rate of SSI occurrence was significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) higher in the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group (31.0%, nine patients) than in the \u003cem\u003eCandida\u003c/em\u003e- group (8.5%, six patients). Other factors related to postoperative complications, including PHLF and postoperative bile leakage, were similar between groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of factors related to postoperative course.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e- group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSSI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePHLF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBile leakage (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative hospital stays (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: SSI, surgical site infection; PHLF, post-hepatectomy liver failure\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePostoperative hospital stay is expressed as the median [25th percentile, 75th percentile].\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results of univariate analysis indicated significant between-group differences in seven items: colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp., anatomical resection, open hepatectomy, postoperative bile leakage, β-D-glucan\u0026thinsp;\u0026ge;\u0026thinsp;3.5 pg/mL, operative time\u0026thinsp;\u0026ge;\u0026thinsp;360 min, and blood loss volume\u0026thinsp;\u0026ge;\u0026thinsp;1000 mL. Multivariate analysis with these factors identified postoperative bile leakage (odds ratio 8.89, 95% CI 1.54\u0026ndash;51.5) and colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e sp. (odds ratio 8.17, 95% CI 1.65\u0026ndash;40.5) as independent predictors (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analyses to identify factors predictive of surgical site infection after hepatectomy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds ratio (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;75 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.90 (0.94\u0026ndash;8.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70 (0.22\u0026ndash;2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u0026thinsp;\u0026gt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.31 (0.07\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV or HCV patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.18 (0.34\u0026ndash;4.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.54 (0.14\u0026ndash;2.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol abuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.64 (0.17\u0026ndash;2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history (*Brinkman index\u0026thinsp;\u0026gt;\u0026thinsp;400)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.67 (0.22\u0026ndash;2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication history of PPI or H2 blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 (0.40\u0026ndash;3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCC patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.74 (0.25\u0026ndash;2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u0026thinsp;\u0026gt;\u0026thinsp;5000 x1000/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.17 (0.39\u0026ndash;3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT\u0026thinsp;\u0026lt;\u0026thinsp;100 x1000/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.44 (0.05\u0026ndash;3.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB\u0026thinsp;\u0026lt;\u0026thinsp;3.5 g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.45 (0.41\u0026ndash;5.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST\u0026thinsp;\u0026gt;\u0026thinsp;30 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.36 (0.77\u0026ndash;7.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT\u0026thinsp;\u0026gt;\u0026thinsp;30 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.22 (0.40\u0026ndash;3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBIL\u0026thinsp;\u0026gt;\u0026thinsp;1.0 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.64 (0.17\u0026ndash;2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u0026thinsp;\u0026lt;\u0026thinsp;75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.07 (0.81\u0026ndash;11.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR\u0026thinsp;\u0026lt;\u0026thinsp;60.1 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.20 (0.37\u0026ndash;3.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u0026thinsp;\u0026gt;\u0026thinsp;0.3 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.45 (0.66\u0026ndash;9.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICGR15\u0026thinsp;\u0026gt;\u0026thinsp;10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.33 (0.44\u0026ndash;4.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-D-Glucan\u0026thinsp;\u0026gt;\u0026thinsp;3.5 pg/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.74 (1.10\u0026ndash;12.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.58 (0.28\u0026ndash;8.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen hepatectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.08 (2.36\u0026ndash;34.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.62 (0.43\u0026ndash;16.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnatomical resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.55 (1.34\u0026ndash;15.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.38 (0.50\u0026ndash;11.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepeat hepatectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.46 (0.12\u0026ndash;1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time\u0026thinsp;\u0026gt;\u0026thinsp;360 minutes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.25 (1.36\u0026ndash;13.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.61 (0.61\u0026ndash;11.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss\u0026thinsp;\u0026gt;\u0026thinsp;1000 mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.75 (1.06\u0026ndash;13.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.99 (0.34\u0026ndash;11.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePHLF grade A or B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.03 (0.21\u0026ndash;5.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative bile leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.50 (3.11\u0026ndash;42.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.89 (1.54\u0026ndash;51.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.87 (1.55\u0026ndash;15.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.17 (1.65\u0026ndash;40.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: BMI, body mass index; HBV, hepatitis B virus; HCV, hepatitis C virus; DM, diabetes mellitus; PPI, proton pump inhibitor; HCC, hepatocellular carcinoma; WBC, white blood cell count; PLT, platelet count; ALB, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; T-BIL, total bilirubin; PT, prothrombin activity; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; ICGR15, indocyanine green retention rate at 15 minutes\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*The Brinkman index is calculated as the number of cigarettes smoked per day multiplied by the number of years of smoking.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the fluctuations in postoperative WBC and CRP level. There were no significant differences in WBC before surgery or on POD 1, 3, 5, and 7. There were no significant differences in CRP levels before surgery or on POD 1, 3, and 5. However, the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group exhibited a significantly higher CRP level on POD 7 (\u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, 5.76 mg/dL vs. \u003cem\u003eCandida\u003c/em\u003e- group, 3.84 mg/dL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we used hepatectomy cases to investigate the relationship between preoperative colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. and the rate of SSI occurrence. Our results revealed that preoperative colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. was an independent predictor of postoperative SSI.\u003c/p\u003e \u003cp\u003e \u003cem\u003eCandida\u003c/em\u003e spp. are frequently detected in samples collected from healthy individuals (oropharynx, 30%; stomach, 47%; jejunum, 54%; ileum, 55%; and fecal, 65%). Although it is a commensal fungus that is usually harmless to the human body, conditions of immunodeficiency (e.g., following infection with the human immunodeficiency virus (HIV), long-term steroid use, and chemotherapy) can lead to opportunistic infections by \u003cem\u003eCandida\u003c/em\u003e spp. Some of these infections can cause severe deterioration in patient health.\u003c/p\u003e \u003cp\u003eThe above findings suggest a close association between immunity and \u003cem\u003eCandida\u003c/em\u003e spp. infections. Several studies using the scoring of immunological vigor[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] have indicated that immunity can be degraded following an increase in the intraoral abundance of \u003cem\u003eCandida\u003c/em\u003e spp. The abundance of \u003cem\u003eCandida\u003c/em\u003e spp. is negatively correlated with the number of T-cells, native T-cells, and CD8\u0026thinsp;+\u0026thinsp;CD28\u0026thinsp;+\u0026thinsp;T-cells, as well as with the ratio of native T-cells to memory T-cells[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The presence of \u003cem\u003eCandida\u003c/em\u003e spp. in the oral cavity may also be a biomarker of HIV infection-induced immunodeficiency. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAs shown above, immunity is associated with the presence of \u003cem\u003eCandida\u003c/em\u003e spp. Accordingly, postoperative infectious complications may also be associated with \u003cem\u003eCandida\u003c/em\u003e spp. \u003cem\u003eCandida\u003c/em\u003e spp. have been shown to infect the drainage sites of patients who underwent pancreaticoduodenectomy; as such, this is considered a risk factor for hemorrhagic complications associated with postoperative pancreatic fistula[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Several studies have also demonstrated the presence of \u003cem\u003eCandida\u003c/em\u003e spp. in the bile of patients who underwent pancreatoduodenectomy, suggesting that this is a significant risk factor of postoperative SSI[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA study on high-level hepato-biliary-pancreatic surgery demonstrated a relationship between the colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. and postoperative SSI[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In that study, colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. was detected in 21/66 patients (31.8%). Postoperative SSI occurred in 57.1% of the patients positive for \u003cem\u003eCandida\u003c/em\u003e colonization of the gastric juice and in 17.8% of patients negative for \u003cem\u003eCandida\u003c/em\u003e spp. colonization (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). In our study, 29/100 patients (29.0%) were positive in the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;group, which is consistent with the result of the previous study. In addition, 31.0% and 8.5% of patients in the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;and \u003cem\u003eCandida\u003c/em\u003e- groups developed SSI. Previous studies examined various surgeries, including hepatectomy, pancreatectomy, bile duct resection, and others. The novelty of our study lies in the fact that we focused specifically on hepatectomy cases, and our findings indicate a strong correlation between the presence of \u003cem\u003eCandida\u003c/em\u003e spp. in the gastric juice and postoperative SSI in hepatectomy cases.\u003c/p\u003e \u003cp\u003eThe mechanism through which colonization of the intragastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. influences the development of SSI remains unknown. \u003cem\u003eCandida\u003c/em\u003e spp. are known to cause damage to mucosal epithelial cells, thus facilitating infections by other microbes[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. They are also considered to directly stimulate the propagation of pathogens such as \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eSerratia marcescens\u003c/em\u003e, and \u003cem\u003eStreptococcus faecalis\u003c/em\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. We did not detect \u003cem\u003eCandida\u003c/em\u003e spp. in any drainage fluids in this study (data not shown). This suggested that \u003cem\u003eCandida\u003c/em\u003e spp. in the gastric juice were not directly responsible for SSI, although they may have stimulated other microbes to cause SSI. The propagation of \u003cem\u003eCandida\u003c/em\u003e spp. is known to cause disturbances in the intestinal flora[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], which is associated with SSI. Thus, \u003cem\u003eCandida\u003c/em\u003e-related disturbances in intestinal flora may be one of the mechanisms underlying SSI[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Several studies have reported that reduced secretion of gastric acid can lead to the propagation of \u003cem\u003eCandida\u003c/em\u003e spp. or disturbances in intestinal flora. Thus, patients with a history of gastrectomy may exhibit reduced gastric acid secretion and were excluded from our study[\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Treatment with PPI or H2 blockers can reduce gastric acid secretion. In this study, the proportion of patients who received PPI or H2 blockers was similar between the \u003cem\u003eCandida\u003c/em\u003e\u0026thinsp;+\u0026thinsp;and \u003cem\u003eCandida\u003c/em\u003e- groups.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, we measured \u003cem\u003eCandida\u003c/em\u003e spp. in the gastric juice, and not in the intraoral cavity (which is much easier to sample). Intraoral conditions can change drastically due to eating, mouth-washing, or teeth-brushing; therefore, measurement under constant conditions is challenging. Moreover, \u003cem\u003eCandida\u003c/em\u003e spp. were detected more frequently in the gastric juice (29/100 cases) than in the oral cavity (9/100 cases). Due to the above reasons, we focused on \u003cem\u003eCandida\u003c/em\u003e spp. colonization in the intra-gastric juice. Second, the presence of \u003cem\u003eCandida\u003c/em\u003e spp. was measured by collecting the gastric juice via a nasogastric tube inserted just after general anesthesia. Although the procedure was patient-friendly, the gastric juice samples could only be collected immediately before surgery. This made is impossible to perform any preoperative interventions. Since the presence of \u003cem\u003eCandida\u003c/em\u003e spp. in the gastric juice contributes to the development of SSI, it is necessary to investigate whether SSI can be reduced through the preoperative use of antimycotic agents. However, the protocol used in this study did not allow the pre-administration of antimycotic agents. A prospective study is needed in which the gastric juice is sampled in advance and antimycotic agents are administered to patients who are positive for the presence of \u003cem\u003eCandida\u003c/em\u003e spp. Finally, this was a single-center study with a limited sample size. A multicenter study with a larger number of cases should be conducted in the future.\u003c/p\u003e \u003cp\u003eIn conclusion, the present study demonstrated that the colonization of the gastric juice by \u003cem\u003eCandida\u003c/em\u003e spp. before hepatectomy may be a predictor of postoperative SSI.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective observational study conformed to the Clinical Research Guidelines and was approved by the ethics committee of our institution (institutional approval number: R2019-138). Written informed consent was obtained from all patients. In addition, this study was registered with UMIN-CTR (identifying number: UMIN 000048860).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Financial Support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHI and MK designed the research and analyzed the patient data. HI, HM, HM, NN, TM, KT, SK, TM, and MT collected the data. HI drafted the manuscript. All authors have read and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of protocol, data, and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol or datasets used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKaibori M, Matsui K, Ishizaki M, Saito T, Kitade H, Matsui Y, Kwon AH (2009) Hepatic resection for hepatocellular carcinoma in the elderly. J Surg Oncol 99(3):154-160. https://doi.org/10.1002/jso.21221\u003c/li\u003e\n\u003cli\u003eIida H, Kaibori M, Matsui K, Ishizaki M, Kon M (2017) Assessing the feasibility of clinicopathological features of hepatic resection for hepatocellular carcinoma in patients over 80 years of age. Mol Clin Oncol 6(1):29-38. https://doi.org/10.3892/mco.2016.1079\u003c/li\u003e\n\u003cli\u003eMirici-Cappa F, Gramenzi A, Santi V, Zambruni A, Di Micoli A, Frigerio M, Maraldi F, Di Nolfo MA, Del Poggio P, Benvegn\u0026ugrave; L, Rapaccini G, Farinati F, Zoli M, Borzio F, Giannini EG, Caturelli E, Bernardi M, Trevisani F (2010) Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience. Gut 59(3):387-396. https://doi.org/10.1136/gut.2009.194217\u003c/li\u003e\n\u003cli\u003eSugawara G, Nagino M, Nishio H, Ebata T, Takagi K, Asahara T, Nomoto K, Nimura Y (2006) Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Ann Surg 244(5):706-714. https://doi.org/10.1097/01.sla.0000219039.20924.88\u003c/li\u003e\n\u003cli\u003eUsami M, Miyoshi M, Kanbara Y, Aoyama M, Sakaki H, Shuno K, Hirata K, Takahashi M, Ueno K, Tabata S, Asahara T, Nomoto K (2011) Effects of perioperative synbiotic treatment on infectious complications, intestinal integrity, and fecal flora and organic acids in hepatic surgery with or without cirrhosis. JPEN J Parenter Enteral Nutr 35(3):317-328. https://doi.org/10.1177/0148607110379813\u003c/li\u003e\n\u003cli\u003eIida H, Sasaki M, Maehira H, Mori H, Yasukawa D, Takebayashi K, Kurihara M, Bamba S, Tani M (2020) The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection. J Clin Biochem Nutr 66(1):67-73. https://doi.org/10.3164/jcbn.19-46\u003c/li\u003e\n\u003cli\u003eOwens WD, Felts JA, Spitznagel EL, Jr. (1978) ASA physical status classifications: a study of consistency of ratings. Anesthesiology 49(4):239-243. https://doi.org/10.1097/00000542-197810000-00003\u003c/li\u003e\n\u003cli\u003eOken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649-655\u003c/li\u003e\n\u003cli\u003eNishigori T, Tsunoda S, Okabe H, Tanaka E, Hisamori S, Hosogi H, Shinohara H, Sakai Y (2016) Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. Annals of Surgical Oncology 23:524-531. https://doi.org/10.1245/s10434-016-5385-y\u003c/li\u003e\n\u003cli\u003eNamm JP, Thakrar KH, Wang CH, Stocker SJ, Sur MD, Berlin J, Dale W, Talamonti MS, Roggin KK (2017) A semi-automated assessment of sarcopenia using psoas area and density predicts outcomes after pancreaticoduodenectomy for pancreatic malignancy. Journal of Gastrointestinal Oncology 8(6):936-944. https://doi.org/10.21037/jgo.2017.08.09\u003c/li\u003e\n\u003cli\u003eKato H, Iizawa Y, Kishiwada M, Usui M, Nakamura A, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Mizuno S, Sakurai H, Isaji S (2016) Negative Impact of Biliary Candidiasis on Early and Late Postoperative Complications After Pancreatoduodenectomy Usefulness of the CHROMagar Candida Plate for Identification. Pancreas 45(9):e45-47. https://doi.org/10.1097/mpa.0000000000000682\u003c/li\u003e\n\u003cli\u003eSato A, Masui T, Nakano K, Sankoda N, Anazawa T, Takaori K, Kawaguchi Y, Uemoto S (2017) Abdominal contamination with Candida albicans after pancreaticoduodenectomy is related to hemorrhage associated with pancreatic fistulas. Pancreatology 17(3):484-489. https://doi.org/10.1016/j.pan.2017.03.007\u003c/li\u003e\n\u003cli\u003eKato H, Iizawa Y, Nakamura K, Gyoten K, Hayasaki A, Fujii T, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Kishiwada M, Mizuo S, Usui M, Sakurai H, Isaji S (2018) The Critical Role of Biliary Candidiasis in Development of Surgical Site Infections after Pancreatoduodenectomy: Results of Prospective Study Using a Selective Culture Medium for Candida Species. Biomed Res Int 2018:5939724. https://doi.org/10.1155/2018/5939724\u003c/li\u003e\n\u003cli\u003eBerr\u0026iacute;os-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, Dellinger EP, Itani KMF, Berbari EF, Segreti J, Parvizi J, Blanchard J, Allen G, Kluytmans J, Donlan R, Schecter WP (2017) Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg 152(8):784-791. https://doi.org/10.1001/jamasurg.2017.0904\u003c/li\u003e\n\u003cli\u003eRahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, B\u0026uuml;chler MW, Weitz J (2011) Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 149(5):713-724. https://doi.org/10.1016/j.surg.2010.10.001\u003c/li\u003e\n\u003cli\u003eKoch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras J, DeMatteo RP, B\u0026uuml;chler MW, Weitz J (2011) Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery 149(5):680-688. https://doi.org/10.1016/j.surg.2010.12.002\u003c/li\u003e\n\u003cli\u003eBaumgartner C, Freydiere AM, Gille Y (1996) Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates. J Clin Microbiol 34(2):454-456. https://doi.org/10.1128/jcm.34.2.454-456.1996\u003c/li\u003e\n\u003cli\u003eHirokawa K, Utsuyama M, Ishikawa T, Kikuchi Y, Kitagawa M, Fujii Y, Nariuchi H, Uetake H, Sugihara K (2009) Decline of T cell-related immune functions in cancer patients and an attempt to restore them through infusion of activated autologous T cells. Mech Ageing Dev 130(1-2):86-91. https://doi.org/10.1016/j.mad.2008.05.001\u003c/li\u003e\n\u003cli\u003eHirokawa K, Utsuyama M, Hayashi Y, Kitagawa M, Makinodan T, Fulop T (2013) Slower immune system aging in women versus men in the Japanese population. Immun Ageing 10(1):19. https://doi.org/10.1186/1742-4933-10-19\u003c/li\u003e\n\u003cli\u003eHayashi K, Tooyama H, Tanaka H, Aizawa H, Shimane T, Kurashina K, Yamada SI, Kurita H (2017) Relationship between the quantity of oral Candida and immunological vigor. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 29(1):65-70. https://doi.org/10.1016/j.ajoms.2016.09.011\u003c/li\u003e\n\u003cli\u003eKorting HC, Ollert M, Georgii A, Fr\u0026ouml;schl M (1988) In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. J Clin Microbiol 26(12):2626-2631. https://doi.org/10.1128/jcm.26.12.2626-2631.1988\u003c/li\u003e\n\u003cli\u003eGyoten K, Kato H, Hayasaki A, Fujii T, Iizawa Y, Murata Y, Tanemura A, Kuriyama N, Kishiwada M, Mizuno S, Usui M, Sakurai H, Isaji S (2021) Association between gastric Candida colonization and surgical site infections after high-level hepatobiliary pancreatic surgeries: the results of prospective observational study. Langenbecks Arch Surg 406(1):109-119. https://doi.org/10.1007/s00423-020-02006-7\u003c/li\u003e\n\u003cli\u003eShirtliff ME, Peters BM, Jabra-Rizk MA (2009) Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol Lett 299(1):1-8. https://doi.org/10.1111/j.1574-6968.2009.01668.x\u003c/li\u003e\n\u003cli\u003eCarlson E (1983) Enhancement by Candida albicans of Staphylococcus aureus, Serratia marcescens, and Streptococcus faecalis in the establishment of infection in mice. Infect Immun 39(1):193-197. https://doi.org/10.1128/iai.39.1.193-197.1983\u003c/li\u003e\n\u003cli\u003eSokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, Cosnes J, Seksik P, Langella P, Skurnik D, Richard ML, Beaugerie L (2017) Fungal microbiota dysbiosis in IBD. Gut 66(6):1039-1048. https://doi.org/10.1136/gutjnl-2015-310746\u003c/li\u003e\n\u003cli\u003eYang AM, Inamine T, Hochrath K, Chen P, Wang L, Llorente C, Bluemel S, Hartmann P, Xu J, Koyama Y, Kisseleva T, Torralba MG, Moncera K, Beeri K, Chen CS, Freese K, Hellerbrand C, Lee SML, Hoffman HM, Mehal WZ, Garcia-Tsao G, Mutlu EA, Keshavarzian A, Brown GD, Ho SB, Bataller R, St\u0026auml;rkel P, Fouts DE, Schnabl B (2017) Intestinal fungi contribute to development of alcoholic liver disease. Journal of Clinical Investigation 127(7):2829-2841. https://doi.org/10.1172/JCI90562\u003c/li\u003e\n\u003cli\u003eShindo K, Fukumura M (1995) Effect of H2-receptor antagonists on bile acid metabolism. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 43(2):170-177\u003c/li\u003e\n\u003cli\u003eShindo K, Machida M, Fukumura M, Koide K, Yamazaki R (1998) Omeprazole induces altered bile acid metabolism. Gut 42(2):266-271. https://doi.org/10.1136/gut.42.2.266\u003c/li\u003e\n\u003cli\u003eBrzozowski T, Zwolinska-Wcislo M, Konturek PC, Kwiecien S, Drozdowicz D, Konturek SJ, Stachura J, Budak A, Bogdal J, Pawlik WW, Hahn EG (2005) Influence of gastric colonization with Candida albicans on ulcer healing in rats: Effect of ranitidine, aspirin and probiotic therapy. Scandinavian Journal of Gastroenterology 40(3):286-296. https://doi.org/10.1080/00365520510011524\u003c/li\u003e\n\u003cli\u003eMartinsen TC, Bergh K, Waldum HL (2005) Gastric juice: A barrier against infectious diseases. Basic and Clinical Pharmacology and Toxicology 96(2):94-102. https://doi.org/10.1111/j.1742-7843.2005.pto960202.x\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Candida, gastric juice, hepatectomy, microflora, surgical site infection","lastPublishedDoi":"10.21203/rs.3.rs-2685128/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2685128/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u003cem\u003e Candida \u003c/em\u003espp. cause opportunistic infections in conditions of immunodeficiency. Here, we investigated the relationship between colonization of the gastric juice by \u003cem\u003eCandida \u003c/em\u003espp. and surgical site infection (SSI) in hepatectomy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Consecutive hepatectomy cases between November 2019 and April 2021 were enrolled. Gastric juice samples (collected intraoperatively through a nasogastric tube) were cultured. We compared factors related to patient background, blood test findings, surgical findings, and postoperative complications between the \u003cem\u003eCandida+\u003c/em\u003egroup (positive for colonization of the gastric juice by \u003cem\u003eCandida \u003c/em\u003espp.) and the \u003cem\u003eCandida- \u003c/em\u003egroup (negative). In addition, we identified the factors that contribute to SSI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e There were 29 and 71 patients in the \u003cem\u003eCandida+ \u003c/em\u003eand \u003cem\u003eCandida-\u003c/em\u003e groups, respectively. The \u003cem\u003eCandida+ group\u003c/em\u003e was significantly older (average age: \u003cem\u003eCandida+\u003c/em\u003e 74 years vs. \u003cem\u003eCandida- \u003c/em\u003e69 years; \u003cem\u003ep\u003c/em\u003e=0.02) and contained more patients who were negative for the hepatitis B and C virus (\u003cem\u003eCandida+\u003c/em\u003e 93% vs. \u003cem\u003eCandida-\u003c/em\u003e 69%; \u003cem\u003ep\u003c/em\u003e=0.02). SSI was significantly more common in the \u003cem\u003eCandida+ group\u003c/em\u003e (\u003cem\u003eCandida+\u003c/em\u003e 31% vs. \u003cem\u003eCandida- \u003c/em\u003e9%; \u003cem\u003ep\u003c/em\u003e=0.01). Postoperative bile leakage and colonization of the gastric juice by \u003cem\u003eCandida \u003c/em\u003espp. were independent predictors of SSI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eColonization of the gastric juice by \u003cem\u003eCandida \u003c/em\u003espp. is a risk factor for SSI after hepatectomy.\u003c/p\u003e","manuscriptTitle":"Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-16 14:42:48","doi":"10.21203/rs.3.rs-2685128/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-04-16T02:56:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-04-15T16:54:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e0477ed0-2089-4563-bc24-5b5143295f81","date":"2023-04-05T23:11:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-03-31T07:35:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"50f13504-9c88-4684-aa7d-6df58dc54b99","date":"2023-03-30T22:45:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-03-30T22:40:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-03-15T06:13:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-03-14T21:57:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2023-03-13T03:10:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"cb66ea03-668d-481d-85fb-b2cb773cdf16","owner":[],"postedDate":"March 16th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:53:35+00:00","versionOfRecord":{"articleIdentity":"rs-2685128","link":"https://doi.org/10.1007/s00423-023-02978-2","journal":{"identity":"langenbecks-archives-of-surgery","isVorOnly":false,"title":"Langenbeck's Archives of Surgery"},"publishedOn":"2023-06-20 21:16:50","publishedOnDateReadable":"June 20th, 2023"},"versionCreatedAt":"2023-03-16 14:42:48","video":"","vorDoi":"10.1007/s00423-023-02978-2","vorDoiUrl":"https://doi.org/10.1007/s00423-023-02978-2","workflowStages":[]},"version":"v1","identity":"rs-2685128","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2685128","identity":"rs-2685128","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}