Bilirubin level in the drainage fluid is an early and independent predictor of clinically relevant bile leakage after hepatic resection

doi:10.1016/j.surg.2012.03.012

Surgery

Volume 152, Issue 5, November 2012, Pages 821-831

https://doi.org/10.1016/j.surg.2012.03.012 Get rights and content

Background

Variations in the definition of bile leakage after hepatic resection have prevented the identification of risk factors for early diagnosis and efficient management. The International Study Group of Liver Surgery (ISGLS) definition standardizes reporting of this complication. It was our aim in the present study to prospectively validate the ISGLS definition of bile leakage after hepatic resection. Furthermore, we sought to identify early predictors of clinically relevant bile leakage.

Methods

A total of 265 patients who underwent elective hepatic resection were enrolled prospectively. Bilirubin concentrations were determined in the serum and drainage fluid until postoperative day 5. Risk factors of Grade B/C bile leakage were assessed by the use of univariate and multivariate analyses.

Results

Grade A, B, and C bile leakage was diagnosed in 23 (8.7%), 38 (14.3%), and 11 (4.1%) patients, respectively. The definition as well as severity grading of bile leakage correlated with the duration of drainage and intensive care unit and hospital stay. Perioperative mortality was 0% for Grade A, 5.2% for Grade B, and 45.4% for Grade C bile leakage (P < .0001). Multivariate analysis confirmed bilirubin concentration in the drainage fluid ≥2.4 mg/dL on postoperative day 2 (odds ratio 11.88; 95% confidence interval 5.33–26.49; P < .0001) and anatomic resection (odds ratio 3.59; 95% CI 1.08–11.97; P = .04) as independent predictors of clinically relevant bile leakage.

Conclusion

The ISGLS definition and severity grading of bile leakage after hepatic resection is clinically meaningful. Bilirubin concentration in the drainage fluid on postoperative day 2 is a strong predictor of clinically relevant bile leakage.

Section snippets

Study design

Patients who were scheduled for hepatic resection at the Department of General, Visceral, and Transplantation Surgery, University of Heidelberg between July 2008 and February 2011 were enrolled in this prospective study. Patients who were scheduled for an emergency procedure were excluded as were patients who were younger than 18 years of age and those with an expected lack of compliance. The study protocol was approved by the ethics committee of the University of Heidelberg.

Blood samples were

Patient characteristics and operative results

A total of 265 patients who underwent elective hepatic resection were enrolled prospectively in the study. The clinicopathologic characteristics of these patients are summarized in Table I. The median age of included patients was 62 (range, 21–88) years and the proportion of male patients was 55.1% (n = 146). The median BMI was 25.6 (range, 15.6–43.5) and 53 (20%) patients had a BMI of ≥30. An ASA class of III or IV was present in 133 (50.3%) patients. The majority of patients had metastatic

Discussion

Bile leakage is a serious complication with potentially severe impact on patients' perioperative and long-term outcome after hepatic resection.¹⁵ However, few studies are available in which authors specifically aimed to reduce the incidence of this complication, as have been attempts to identify early predictors of bile leakage that might allow rapid diagnosis and efficient management. In part this may be explained by the lack of a uniform definition of this complication. The development of the

References (51)

J. Belghiti et al.
Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection
J Am Coll Surg
(2000)
D.N. Reed et al.
Decreasing mortality of bile leaks after elective hepatic surgery
Am J Surg
(2003)
S. Bhattacharjya et al.
Outcome of early endoscopic biliary drainage in the management of bile leaks after hepatic resection
Gastrointest Endosc
(2003)
S. Tanaka et al.
Incidence and management of bile leakage after hepatic resection for malignant hepatic tumors
J Am Coll Surg
(2002)
L. Vigano et al.
Bile leak after hepatectomy: predictive factors of spontaneous healing
Am J Surg
(2008)
M. Koch et al.
Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery
Surgery
(2011)
P. Bedossa et al.
An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group
Hepatology
(1996)
M. Schiesser et al.
Perioperative morbidity affects long-term survival in patients following liver resection for colorectal metastases
J Gastrointest Surg
(2008)
R.T. Poon et al.
Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database
Ann Surg
(2004)
W.R. Jarnagin et al.
Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade
Ann Surg
(2002)

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Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation.
We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group.
The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P < .05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P < .0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P < .0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P < .001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P < .001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P = .03)
The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition.
Improved management of grade B biliary leaks after complex liver resections using gadoxetic acid disodium–enhanced magnetic resonance cholangiography
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Bile leaks occurring after complex liver resection and lasting >1 week (grade B) usually are managed by means of invasive cholangiography either endoscopic or percutaneous, with a substantial risk of procedure-related complications. The aim of this study was to investigate the ability of gadoxetic acid disodium–enhanced magnetic resonance cholangiography to detect postoperative biliary leaks and avoid invasive cholangiography in case of peripheral location of the fistula.
Patients with grade B biliary leak after complex liver resection from January 2018 to March 2020 underwent magnetic resonance cholangiography to guide the management of the leak (study group). The primary endpoint was the ability of magnetic resonance cholangiography to reduce the need for invasive cholangiography with respect to similar posthepatectomy leaks collected in the previous 2 years and approached with upfront invasive cholangiography (controls). A series of in-hospital outcomes also were compared.
Out of 533 liver resections, 11 study patients versus 11 control patients with grade B leaks were compared. Magnetic resonance cholangiography achieved 100% accuracy in detection and location of the leak. Five out of 6 peripheral leaks healed without invasive cholangiography. Overall, 50% reduction in the use of invasive cholangiography was observed in the study versus control patients. Median healing time and hospital stay were 38 and 40 days in patients undergoing invasive cholangiography versus 10 and 11 days in patients treated conservatively (P = .007 and 0.012, respectively). Infection rate and other complications rate were 82% vs 20% (P = .01) and 35% vs 40% (P = .5), respectively.
Magnetic resonance cholangiography is a safe, precise, noninvasive tool to detect posthepatectomy bile leaks that can help clinicians in decision-making on conservative versus invasive treatment of fistulas.
Development and validation of the bile leakage grading criterion in patients following Roux-en-Y hepaticojejunostomy
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The present research aimed to propose a severity grading criterion for bile leakage in pediatric patients after Roux-en-Y hepaticojejunostomy for choledochal cysts.
Despite a bile leakage classification system from the International Study Group of Liver Surgery (ISGLS) has been developed, a commonly used grading system for pediatric patients after Roux-en-Y hepaticojejunostomy has not yet been established.
A review of clinical, laboratory, and ultrasonographic parameters were used to develop a grading system for classifying the severity of bile leakage. A total of 267 patients with bile leakage were retrospectively assessed to review the system.
We developed a grading system for bile leakage severity for use in pediatric patients following Roux-en-Y hepaticojejunostomy. By applying the criteria to 267 patients, grade I, II, or III bile leakage was determined in 103 patients (8.7%), 115 patients (9.8%), and 49 patients (4.2%) patients, respectively. The most severe bile leakage grade (grade III), was associated with significantly higher γ-glutamyl transpeptidase and amylase levels, greater drain fluid output, more intensive care unit (ICU) admissions, and longer postoperative hospital stay. Interestingly, patients with grade II leakage who underwent reoperation had significantly more ICU admissions, longer postoperative hospital stays (p < 0.05), and higher overall hospitalization cost (p < 0.05) compared with those who underwent conservation management. Of the patients with bile duct stricture and common bile duct (CBD) stones, there were no differences among the different grades of postoperative bile leakage.
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Several modalities are used to improve the outcome of liver resection surgery. Laser-based surgery may become promising option; therefore we aim to report our experience regarding the efficacy and safety of Thulium-Doped Fiber Laser (TDFL) 1940 nm in liver parenchyma resection.
A cross sectional study in which patients with pre-existing liver pathology during July 2019 and July 2020 were randomly assigned to receive liver resection using TDFL integrated with raman laser emitting at 1940 nm and 1470 nm wavelength. Data on estimated blood loss during liver transection, liver transection speed, morbidity rate, and postoperative variables including complications, length of hospital stay (days), and mortality were analyzed.
A total of 17 consecutive liver resections were performed, among them are 7 major and 11 minor hepatectomies. The Multipulse TM+1470 were used on 8 procedures consisted of 1 major and 7 minor hepatectomies, the mean amount of blood loss during operation and liver transection was 628.13 ± 141.31 mL and 294.63 ± 94.81 ml, respectively. The mean liver transection speed was 1.52 ± 0.27 cm²/min. No biliary leak, post-hepatectomy-liver failure, and mortality were reported.
TDFL provided by Multipulse TM+1470 is an effective and safe tool for liver surgery, providing good hemostasis and allowing for safe and effective exposure of vascular. Further study with larger samples might be needed proved the efficacy and safety of TDFL in liver surgery.
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A total of 101 patients were enrolled in this trial, giving 51 patients in the BioFoam® group and 50 patients in the control group (without use of BioFoam®). Time-to-complete hemostasis was significantly reduced in the BioFoam® group (156 ± 129 versus 307 ± 264 s; P = 0.001). There were no significant differences in postoperative bile leaks (n = 6 (12%) vs. n = 5 (10%); P = 0.776), postoperative morbidity (n = 37 (73%) vs. n = 40 (80%); P = 0.482) or mortality (n = 3 (6%) vs. n = 1 (2%); P = 0.618) between groups.
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Citation Excerpt :
In 2011, the International Study Group of Liver Surgery (ISGLS) proposes a uniform definition and severity grading of BL after hepatobiliary and pancreatic operative therapy.27 Rahhari and colleagues have reported that this definition as well as severity grading of BL correlated with the short-term outcomes like duration of drainage, intensive care unit and hospital stay.8 However, using this severity grading of BL, most of the BL would be classified as Grade B.38–40 What's more, the criterion of the severity grading is based on the impact of BL on patients' clinical management, which cannot reflect the impact of BL on long-term prognosis.
The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear.
One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared.
The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p < 0.001). Compared with the patients without BL, the patients with BL had a higher level of IL-6 from postoperative day (POD) 1 to POD 60, and a higher level of CRP from POD 7 to POD 60. By POD 60, the levels of IL-6 and CRP hadn't restored to the normal level in the LTBL group.
The LTBL has a negative impact on the long-term prognosis of patients with primary liver cancers after hepatectomy, in which the inflammatory responses may play a pivotal role.

View all citing articles on Scopus

: Dr Rahbari and Dr Elbers contributed equally to this work.

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Original CommunicationBilirubin level in the drainage fluid is an early and independent predictor of clinically relevant bile leakage after hepatic resection

Background

Methods

Results

Conclusion

Section snippets

Study design

Patient characteristics and operative results

Discussion

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Am J Surg

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J Am Coll Surg

Am J Surg

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Original Communication
Bilirubin level in the drainage fluid is an early and independent predictor of clinically relevant bile leakage after hepatic resection