Microbe Isolation from Blood,Central Venous Catheters,and Fluid Collections after Liver Resections

Abstract

Background:

Our goal was to evaluate the microbe species responsible for bacteremia or infections related to central venous catheter (CVC) or fluid collections after liver resection.

Patients and Methods:

Data from 112 patients (68 males, 44 females) who underwent liver resection over a period of 63 months were reviewed. Patient and tumor characteristics, intra-operative and post-operative data, and the results from cultures of peripheral blood, CVC tips and drained intra-abdominal or intra-throracic fluid collections were collected.

Results:

There were positive blood cultures in 20 patients (17.9%). Coagulase-negative staphylococci (CoNS) and bacteria of enteric flora were the micro-organisms found most frequently and half of the cases had multiple isolated microbe species. The construction of a bilioenteric anastomosis was an independent risk factor for microbe isolation in peripheral blood (odds ratio [OR]: 11, p = 0.01). Furthermore, there were positive cultures of the CVC tip in 14 patients (12.5%), with CoNS being the micro-organism found most frequently and most cases had only one isolated microbe species. No specific risk factor for catheter-related infections was detected. In addition, there were positive cultures of drained fluid collections in 19 patients (17%), with bacteria of enteric flora being the micro-organisms found most frequently and the majority of cases had multiple isolated microbe species. The construction of a bilioenteric anastomosis (OR: 23.5, p = 0.002) and the laparoscopic approach (OR: 4.7, p = 0.0496) were independent risk factors for microbe isolation in drained fluid collections. Finally, the presence of positive blood cultures was associated with the presence of positive culture of CVC tips (p = 0.018) and drained fluid collections (p = 0.001).

Conclusions:

Post-operative bacteremia, colonization of CVCs, and contamination of fluid collections occur frequently after liver resections and various microbe species may be involved. Patients who undergo hepatectomy and a synchronous construction of a bilioenteric anastomosis are at increased risk of bacteremia development and contamination of fluid collections.

Liver resections have become more widespread during the last decades because of expansion of eligibility criteria and surgical techniques. New and more sophisticated modalities have been added to the arsenal available to hepatobiliary surgeons. However, despite the advances in the field of hepatic surgery, post-operative morbidity and mortality remain relatively high, with mortality rates between 0.3% and 9.7% and morbidity rates between 4.1% and 47.7% [1 –3]. Infectious complications are responsible for a great proportion of post-operative morbidity, with surgical site infection, pneumonia, urinary tract infection, intra-abdominal abscess, and central venous catheter (CVC)-related infection being among the most common. There is a wide range of micro-organisms implicated in the pathogenesis of the infectious complications after hepatectomy, which may result in septicemia, severe sepsis, and septic shock [1 –3]. The goal of this study was to evaluate the species that are responsible for bacteremia or infections related to CVC or fluid collections in patients having undergone liver resection, how often they are isolated from the peripheral blood, the CVC tips, or the drained intra-abdominal or intra-thoracic fluid collections, and whether there are any risk factors rendering patients more susceptible to these infectious complications.

Patients and Methods

We reviewed our prospectively maintained database of patients who underwent liver resections by a senior hepatobiliary surgeon in our department. One hundred thirty-five patients with hepatobiliary pathology underwent liver resection in our department over a period of 63 months. Patients having undergone additional synchronous procedures other than hepatobiliary ones were excluded from this study in order to rule out cases of post-operative infections that could be attributed to the additional procedures. We also excluded from this study patients who had undergone pre-operative biliary drainage, because it rses the possibility of post-operative infections caused by exposure of the biliary tree to microbes of enteric flora [4,5], in order to rule out those infections that could be attributed to the already existing drainage of bile ducts. We omitted the aforementioned cases because we wanted to avoid these confounding factors and concentrate on the effect of hepatobiliary procedures on the investigated infections itself. Thus, 112 of the 135 patients were finally included in this study. All patients received peri-operative antibiotic prophylaxis and a CVC was inserted at the right or the left internal jugular vein of all patients at the beginning of the operation. We collected data regarding patients' gender and age, presence of liver cirrhosis, type of tumor, number and size of lesions, whether the operation was open or laparoscopic, whether a major hepatectomy was performed (three or more liver segments), whether a bilioenteric anastomosis was constructed, whether patients stayed in the intensive care unit post-operatively (ICU), and results of peripheral blood cultures, cultures of CVC tip, and cultures of drained intra-abdominal or intra-thoracic fluid collections. A peripheral blood culture was taken and the CVC tip was cultured when a temperature of 38°C or higher was noted post-operatively, whereas samples from every drained intra-abdominal or intra-thoracic fluid collection were cultured. This study conforms to the Declaration of Helsinki and the guidelines of the ethical committee of our institution.

Statistical analysis

Comparisons among groups with categorical variables were made using χ² test and Fisher exact test. When the dependent outcome was a categorical dichotomous variable multivariable analysis was performed using logistic regression analysis with the forward conditional method. All the tests were two-tailed. Results were considered statistically significant if the p value was less than 0.05.

Results

Patients' characteristics and isolated microbes

One hundred twelve patients (68 males and 44 females) underwent liver resection for various hepatobiliary pathologies. The mean age was 59.7 years (standard deviation [SD]: 13.6 years) and the median age was 61 years (range, 19–89 years). Table 1 shows patients' and tumor characteristics, as well as intra-operative and post-operative data. There were positive blood cultures in 20 of the 112 patients (17.9%). Various microbe species were isolated from peripheral blood cultures, with coagulase-negative staphylococci (CoNS) and bacteria of enteric flora being the micro-organisms found most frequently. Only one microbe species was detected in half of patients with positive blood cultures (10/20; 50%), whereas more than one microbe species were detected in the other half (10/20; 50%). Moreover, there were positive cultures of CVC tip in 14 of the 112 patients (12.5%). Various microbe species were isolated from cultures of CVC tips, with CNS being the micro-organism found most frequently. Only one microbe species was detected in most patients with positive cultures of CVC tips (12/14; 85.7%), whereas more than one microbe species were detected in two patients only (2/14; 14.3%). In addition, there were positive cultures of drained fluid collections in 19 of the 112 patients (17%). Various microbe species were isolated from cultures of samples from drained intra-abdominal or intra-thoracic fluid collections, with bacteria of enteric flora being the micro-organisms found most frequently. More than one microbe species was detected in the majority of patients with positive cultures of drained fluid collections (11/19; 57.9%). Table 2 shows the exact micro-organisms that were found in peripheral blood, CVC tips, and samples from drained fluid collections.

Table 1.

Patients', Tumor, Intra-Operative and Post-Operative Data (n = 112)

Gender	Male: 68 (60.7%); female: 44 (39.3%)
Age	Mean ± SD: 59.7 y ± 13.6
Age	Median (min-max): 61 y (range, 19–89)
Liver cirrhosis	Yes: 13 (11.6%); no: 99 (88.4%)
Type of tumor	Hepatocellular carcinoma: 37 (33%)
	Cholangiocarcinoma: 30 (26.8%)
	Intra-hepatic: 22 (19.6%)
	Hilar: 8 (7.1%)
	Liver metastases: 27 (24.1%)
	Other: 18 (16.1%)
Number of lesions	Solitary: 85 (75.9%); multiple: 27 (24.1%)
Maximum tumor diameter	Mean ± SD: 6.2 cm ±4.4 cm
Maximum tumor diameter	Median (min-max): 5 cm (0.4–22)
Type of operation	Open: 91 (81.25%), Laparoscopic: 21 (18.75%)
Extent of hepatectomy	Major: 40 (35.7%); minor: 72 (64.3%)
Bilioenteric anastomosis	Yes: 10 (8.9%); no: 102 (91.1%)
ICU stay	Yes: 22 (19.6%); no: 90 (80.4%)
Positive blood culture	Yes: 20 (17.9%); no: 92 (82.1%)
Positive culture of CVC tip	Yes: 14 (12.5%); no: 98 (87.5%)
Positive culture of drained fluid collection	Yes: 19 (17%), No: 93 (83%)

SD = standard deviation; ICU = intensive care unit, CVC = central venous catheter.

Table 2.

Isolated Microbes

Peripheral blood (n = 20)
Gram-positive bacteria	14 (70%)
Coagulase-negative staphylococci	8 (40%)
Enterococcus faecalis	3 (15%)
Enterococcus faecium	3 (15%)
Staphylococcus epidermidis	2 (10%)
Gram-negative bacteria	14 (70%)
Klebsiella pneumoniae	6 (30%)
Acinetobacter baumannii	4 (20%)
Escherichia coli	3 (15%)
Pseudomonas aeruginosa	2 (10%)
Enterobacter cloacae	1 (5%)
^*Multiple microbes: 10 (50%)

Central venous catheter tips (n = 14)
Gram-positive bacteria	12 (85.7%)
Coagulase-negative staphylococci	12 (85.7%)
Gram-negative bacteria	4 (28.6%)
Acinetobacter baumannii	2 (14.3%)
Klebsiella pneumoniae	1 (7.1%)
Pseudomonas aeruginosa	1 (7.1%)
^*Multiple microbes: 2 (14.3%)

Drained fluid collections (n = 19)
Gram-positive bacteria	14 (73.7%)
Enterococcus sp.	11 (57.9%)
Coagulase-negative staphylococci	5 (26.3%)
Staphylococcus aureus	1 (5.3%)
Gram-negative bacteria	14 (73.7%)
Klebsiella pneumoniae	5 (26.3%)
Escherichia coli	4 (21.1%)
Enterobacter cloacae	4 (21.1%)
Pseudomonas aeruginosa	3 (15.8%)
Acinetobacter baumannii	3 (15.8%)
Klebsiella oxytoca	1 (5.3%)
Serratia marcescens	1 (5.3%)
Stenotrophomonas maltophilia	1 (5.3%)
^*Multiple microbes: 11 (57.9%)

Associations regarding peripheral blood cultures

There were statistically significant associations concerning the type of tumor, the extent of hepatectomy, the construction of bilioenteric anastomosis, and the post-operative stay in ICU in univariate analysis. First, positive blood cultures were documented more frequently in patients with cholangiocarcinoma (11/30; 36.7%) than in patients with hepatocellular carcinoma (5/37; 13.5%) or liver metastases (1/27; 3.7%; p = 0.005). Furthermore, cases of major liver resection had positive blood cultures more often (12/40; 30%) than cases of minor liver resections (8/72; 11.1%; p = 0.012). In addition, cases with operations including a bilioenteric anastomosis showed a higher rate of isolated microbes from peripheral blood (6/10; 60%) than those without (14/102; 13.7%; p = 0.002). Finally, there was an increased rate of microbe isolation in peripheral blood of patients who had to stay in ICU post-operatively, usually for one or two days (8/22; 36.4%), compared with that of patients who did not stay in ICU post-operatively (12/90; 13.3%; p = 0.011). On the other hand, there were no significant associations between blood cultures and gender (p = 0.942), age (p = 0.147), presence of liver cirrhosis (p = 0.244), presence of multiple lesions (p = 0.393), maximum tumor diameter (p = 0.955), or type of operation (open or laparoscopic; p = 0.356) in univariable analysis. However, only the construction of bilioenteric anastomosis was an independent risk factor for isolation of microbes from peripheral blood post-operatively in multivariable analysis (OR: 11, 95% confidence interval [CI]: 1.771–68.314, B: 2.398, SE: 0.932, Wald: 6.623, p = 0.01). The results of multivariate analysis are listed in Table 3.

Table 3.

Multivariable Analysis

Parameter	Positive peripheral blood culture (p value)	Positive culture of CVC tips (p value)	Positive culture of drained fluid collections (p value)
Gender (male/female)	0.839	0.602	0.613
Age (>65 y/≤65 y)	0.245	0.701	0.745
Liver cirrhosis (yes/no)	0.056	0.724	0.328
Type of tumor (HCC/CC/LM)	0.286	0.811	0.55
Number of lesions (multiple/solitary)	0.778	0.199	0.275
Maximum tumor diameter (>5 cm/≤5 cm)	0.932	0.773	0.461
Type of operation (laparoscopic/open)	0.898	0.69	0.0496 (OR: 4.7)
Extent of hepatectomy (major/minor)	0.572	0.459	0.709
Bilioenteric anastomosis (yes/no)	0.01 (OR: 11)	0.074	0.02 (OR: 23.5)
ICU stay (yes/no)	0.061	0.586	0.888

CVC = central venous catheter; HCC = hepatocellular carcinoma; CC = cholangiocarcinoma; LM = liver metastases; OR = odds ratio; ICU = intensive care unit.

Associations regarding cultures of CVC tips

No significant associations were detected between the isolation of microbes from CVC tips and any tested parameter, namely gender (p = 0.38), age (p = 0.769), presence of liver cirrhosis (p = 1), type of tumor (p = 0.139), number of lesions (p = 0.512), size of lesions (p = 1), type of operation (open or laparoscopic) (p = 0.724), extent of hepatectomy (major or minor; p = 0.247), construction of bilioenteric anastomosis (p = 0.11), or ICU stay (p = 0.47) in univariable analysis. The same lack of significant associations was confirmed in multivariable analysis. The results of multivariable analysis are listed in Table 3.

Associations regarding cultures of drained fluid collections

There was a higher rate of isolated microbes from drained fluid collections in cases with operations including a bilioenteric anastomosis (6/10; 60%) than in those without (13/102; 12.7%; p = 0.002) in univariable analysis. The construction of bilioenteric anastomosis remained an independent risk factor for isolation of microbes from drained fluid collections post-operatively in multivariable analysis (OR: 23.5, 95% CI: 3.242–170.324, B: 3.157, SE: 1.011, Wald: 9.759, p = 0.002). There was also an increased rate of isolated microbes from drained fluid collections in patients who underwent laparoscopic hepatectomy (5/21; 23.8%) compared with patients who underwent open hepatectomy (14/91; 15.4%), but this difference was not significant in univariable analysis (p = 0.347). Nevertheless, multivariable analysis revealed the laparoscopic approach as an independent risk factor for isolation of microbes from drained fluid collections post-operatively on the verge of statistical significance (OR: 4.7, 95% CI: 1.003-22.03, B: 1.548, SE: 0.788, Wald: 3.855, p = 0.0496). On the other hand, there were no significant associations between cultures of drained fluid collections and gender (p = 0.811), age (p = 0.442), presence of liver cirrhosis (p = 0.46), type of tumor (p = 0.253), number of lesions (p = 0.556), size of lesions (p = 0.512), extent of hepatectomy (major or minor; p = 0.245), or ICU stay (p = 0.202) in univariable analysis, which was confirmed in multivariable analysis. The results of multivariable analysis are listed in Table 3.

Associations among cultures of peripheral blood, CVC tips and drained fluid collections

There was a significant association between the presence of positive blood culture and the presence of positive culture of CVC tips, because there were six patients who had positive blood culture (6/20) and positive culture of CVC tips (6/14) as well (p = 0.018). However, there was considerable discrepancy in the isolated microbe species between blood cultures and cultures of CVC tips. In particular, the only micro-organism that was isolated from both the peripheral blood and the CVC tip was CoNS in four patients. There was also a significant association between the presence of positive blood culture and the presence of positive culture of drained fluid collection, because there were nine patients who had positive blood culture (9/20) and positive culture of drained fluid collection (9/19) as well (p = 0.001). In all these nine cases, there was at least one micro-organism that was isolated in both the peripheral blood and the drained fluid collection. On the contrary, no significant association was detected between the presence of positive culture of CVC tip and the presence of positive culture of drained fluid collection, because there were only four patients who had positive culture of CVC tip (4/14) and positive culture of drained fluid culture (4/19) as well (p = 0.252). Moreover, there was great discrepancy in the isolated microbe species between cultures of CVC tips and cultures of drained fluid collections. In particular, there was only one case in which the same microorganism, which was CoNS, was isolated from both the CVC tip and the drained fluid collection.

Discussion

Infectious complications are a frequent reason of post-operative morbidity [1 –3]. The incidence of post-operative bacteremia in patients who underwent liver resection ranges between 3.3% and 17.5% [6 –9], whereas the incidence of post-operative microbe isolation from the CVC tip ranges between 1.6% and 5% [8 –13]. Moreover, the incidence of contaminated intra-abdominal fluid collections, and organ/space surgical site infections (SSIs) in general after hepatectomy is estimated between 4% and 11.1% [9,12,14 –19]. In addition, contaminated pleural effusion is a potential post-operative complication after hepatectomy and the possibility of a patient suffering from pleural empyema after liver resection is estimated at approximately 1% [20].

A variety of microbe species have been isolated in the blood stream of patients having undergone hepatectomy and presenting an infectious complication. Gram-positive bacteria are detected in 41.9%–71.4% of cases with bacteremia, such as Staphylococcus aureus, Staphylococcus epidermidis, CoNS, Streptococcus bovis, Enterococcus faecium, Enterococcus faecalis, Enterococcus avium, etc. Gram-negative bacteria are detected in 26.7%–53.2% of cases with bacteremia, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Stenotrophomonas maltophilia, etc. Moreover, fungi, such as Candida albicans, are found in the blood stream at a lower rate, approximately 4.8%–14.3% of patients with bacteremia. Cases with mixed bacteremia, with more than one microbe isolated in peripheral blood, correspond to 14.3%–17.7% of patients with positive blood cultures [6,7,9]. Similarly, a variety of microbe species of the enteric flora have been isolated in samples of intra-abdominal fluid collections, and organ/space surgical site infections in general, such as Enterococcus sp., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter sp., Serratia marcescens, etc., as well as species of Staphylococcus (CoNS and Staphylococcus aureus) and Streptococcus [9,14,15,18].

Regarding risk factors for bacteremia and organ/space SSIs after hepatectomy, findings are controversial. In particular, Shigeta et al. [7] indicated older age, longer duration of operation, major hepatectomy, and presence of pre-operative obstructive jaundice as risk factors for the development of post-operative bacteremia, whereas Karavokyros et al. [9] reported only ICU stay as a risk factor for the emergence of post-operative infections. Several risk factors for the development of post-operative organ/space SSIs have also been identified, but with each study reporting a different combination. Thus, presence of liver cirrhosis, presence of hepatolithiasis, pre-existing bilioenteric anastomosis, higher blood loss, longer operative times, post-operative bile leakage, liver re-operation, hypoalbuminemia, hyperbilirubinemia, hyponatremia, pre-operative liver-directed chemotherapy, and synchronous bowel operation have been associated with post-operative organ/space SSIs in one or more studies [15 –19]. In addition, the presence of infected ascites or intra-abdominal collections predisposes to the development of contaminated pleural effusion [20]. A lot of clinical research has also been conducted in regards to the role of pre-operative biliary drainage in the development of post-operative infectious complications. It seems that pre-operative biliary drainage increases the possibility of post-operative infections caused by exposure of the biliary tree to microbes of enteric flora [4,5]. The same mechanism is responsible for the increased rates of SSIs noted in patients with a pre-existing bilioenteric anastomosis who undergo liver resection [15].

We have observed a rate of 17.9% in terms of post-operative bacteremia and a rate of 12.5% in terms of post-operative CVC colonization after liver resections. We have also noted a rate of 17% in regards to post-operative contaminated fluid collections. The isolation of multiple microbe species was common in cases of bacteremia and contaminated drained fluid collections. On the contrary, only one microbe species was isolated from CVC tip in most cases with colonization of CVC tip. Coagulase-negative staphylococci and bacteria of enteric flora were detected mostly in peripheral blood. Bacteria of enteric flora were also the micro-organisms that were found most frequently in samples from drained fluid collections. Moreover, CoNS was the micro-organism that was isolated from CVC tips in most cases. The frequent detection of CoNS in peripheral blood and CVC tips and its isolation in samples from drained fluid collections raises the suspicion of contamination at the time of culture or breaks in the sterile technique during operation or CVC insertion. Nevertheless, several studies have reported the frequent detection of CoNS in peripheral blood, CVC tips, and fluid collections after liver resections [6,9,15].

According to our findings, major hepatectomy, ICU stay, presence of cholangiocarcinoma, and construction of bilioenteric anastomosis are associated with a higher risk of developing post-operative bacteremia. However, only the construction of a bilioenteric anastomosis is an independent risk factor for microbe isolation in the peripheral blood of patients who underwent hepatectomy. Moreover, the construction of a bilioenteric anastomosis seems to be an independent risk factor for post-operative contamination of fluid collections, along with the laparoscopic approach, with the second one contradicting the findings of recent studies, which report that the rates of organ/space SSIs are lower after laparoscopic than after open hepatectomies [21 –23]. The connection between bilioenteric anastomosis on the one hand and bacteremia and contaminated fluid collections on the other hand is probably a result of the exposure of the biliary tree to microbes of enteric flora, because this reflux is not prevented by the sphincter of Oddi anymore. The ascent of enteric bacteria in the biliary tree leads to bactibilia, which in turn results in ascending cholangitis and bacteremia, as it has been shown by experimental studies [24,25] and also predisposes to organ/space SSIs, as has been indicated by clinical studies [15]. On the contrary, we did not find any specific risk factors for catheter-related infections, as far as parameters of liver resections are concerned. Finally, the presence of positive blood cultures was associated with the presence of positive culture of CVC tips and drained fluid collections. The same micro-organisms were often isolated from peripheral blood and drained fluid collections. On the contrary, different microbe species were usually isolated from peripheral blood and CVC tips. This leads to the conclusion that microbes located in contaminated fluid collections may enter the blood stream more frequently than microbes colonizing CVCs.

In conclusion, post-operative bacteremia, colonization of CVCs and contamination of fluid collections occur frequently after liver resections. Hepatobiliary surgeons should be aware of these potential post-operative infectious complications and the fact that they are often multimicrobial and various microbe species may be involved. A high clinical suspicion is required in order for these to be identified and treated promptly. They should also keep in mind that the patients who undergo hepatectomy and a synchronous construction of a bilioenteric anastomosis are at increased risk of bacteremia development and contamination of fluid collections.

Footnotes

Acknowledgment

The authors would like to thank Mr. Dimitrios Fourkas for his valuable help in collecting the microbiological data.

Author Disclosure Statement

The authors declare that there are no conflicts of interest.

References

Ishii

, Mizuguchi

, Harada

, et al. Comprehensive review of post-liver resection surgical complications and a new universal classification and grading system. World J Hepatol, 2014; 6:745–751.

Jin

, Fu

, Wuyun

. Management of post-hepatectomy complications. World J Gastroenterol, 2013; 19:7983–7991.

van den Broek

, van Dam

, Malagó

, et al. Feasibility of randomized controlled trials in liver surgery using surgery-related mortality or morbidity as endpoint. Br J Surg, 2009; 96:1005–1014.

Liu

, Li

, Wei

, Li

. Preoperative biliary drainage before resection for hilar cholangiocarcinoma: Whether or not? A systematic review. Dig Dis Sci, 2011; 56:663–672.

Celotti

, Solaini

, Montori

, et al. Preoperative biliary drainage in hilar cholangiocarcinoma: Systematic review and meta-analysis. Eur J Surg Oncol, 2017; 43:1628–1635.

Raymond

, Pelletier

, Crabtree

, et al. Impact of bloodstream infection on outcomes among infected surgical inpatients. Ann Surg, 2001; 233:549–555.

Shigeta

, Nagino

, Kamiya

, et al. Bacteremia after hepatectomy: An analysis of a single-center, 10-year experience with 407 patients. Langenbecks Arch Surg, 2002; 387:117–124.

Jannasch

, Kelch

, Adolf

, et al. Nosocomial infections and microbiologic spectrum after major elective surgery of the pancreas, liver, stomach, and esophagus. Surg Infect, 2015; 16:338–345.

Karavokyros

, Orfanos

, Angelou

, et al. Incidence and risk factors for organ/space infection after radiofrequency-assisted hepatectomy or ablation of liver tumors in a single center: More than meets the eye. Front Surg, 2017; 4:17.

10.

Togo

, Matsuo

, Tanaka

, et al. Perioperative infection control and its effectiveness in hepatectomy patients. J Gastroenterol Hepatol, 2007; 22:1942–1948.

11.

Uchiyama

, Ueno

, Ozawa

, et al. Risk factors for postoperative infectious complications after hepatectomy. J Hepatobiliary Pancreat Sci, 2011; 18:67–73.

12.

Pessaux

, van den Broek

, Wu

, et al. Identification and validation of risk factors for postoperative infectious complications following hepatectomy. J Gastrointest Surg, 2013; 17:1907–1916.

13.

Zhou

, Chen

, Li

, et al. Preoperative antibiotic prophylaxis does not reduce the risk of postoperative infectious complications in patients undergoing elective hepatectomy. Dig Dis Sci, 2016; 61:1707–1713.

14.

, Ding

, Han

, Wu

. A nomogram prediction of postoperative surgical site infections in patients with perihilar cholangiocarcinoma. Medicine (Baltimore), 2017; 96:e7198.

15.

Matsumura

, Saiura

, Inoue

, et al. High rate of organ/space surgical site infection after hepatectomy with preexisting bilioenteric anastomosis. World J Surg, 2016; 40:937–945.

16.

Kokudo

, Uldry

, Demartines

, Halkic

. Risk factors for incisional and organ space surgical site infections after liver resection are different. World J Surg, 2015; 39:1185–1192.

17.

Yang

, Tu

, Zhang

, et al. Risk factors of surgical site infection after hepatic resection. Infect Control Hosp Epidemiol, 2014; 35:317–320.

18.

Sadamori

, Yagi

, Shinoura

, et al. Risk factors for organ/space surgical site infection after hepatectomy for hepatocellular carcinoma in 359 recent cases. J Hepatobiliary Pancreat Sci, 2013; 20:186–196.

19.

Moreno Elola-Olaso

, Davenport

, Hundley

, et al. Predictors of surgical site infection after liver resection: A multicentre analysis using National Surgical Quality Improvement Program data. HPB (Oxford), 2012; 14:136–141.

20.

Goumard

, Fuks

, Cauchy

, et al. Pleural empyema following liver resection: a rare but serious complication. World J Surg, 2016; 40:2999–3008.

21.

Bagante

, Spolverato

, Strasberg

, et al. Minimally invasive vs. open hepatectomy: A comparative analysis of the National Surgical Quality Improvement Program Database. J Gastrointest Surg, 2016; 20:1608–1617.

22.

López-Ben

, Palacios

, Codina-Barreras

, et al. Pure laparoscopic liver resection reduces surgical site infections and hospital stay. Results of a case-matched control study in 50 patients. Langenbecks Arch Surg, 2014; 399:307–314.

23.

Nanashima

, Arai

, Oyama

, et al. Associated factors with surgical site infections after hepatectomy: Predictions and countermeasures by a retrospective cohort study. Int J Surg, 2014; 12:310–314.

24.

Chuang

, Lee

, Shieh

, et al. Reappraisal of the role of the bilioenteric conduit in the pathogenesis of postoperative cholangitis. Pediatr Surg Int, 2000; 16:29–34.

25.

Hsieh

, Huang

, et al. Bacteria ascend to liver from the bilioenteric conduit after choledochojejunostomy in the cholestatic rat. Pediatr Surg Int, 2003; 19:699–702.