Abstract
Background:
There are several methods used to extract common bile duct (CBD) stones encountered during cholecystectomy. Intraoperative cholangiotomy, cholangioscopy, and laparoscopic CBD exploration (LCBDE) are techniques that allow removal of stones from the CBD during the index procedure. However, bile leakage following CBD exploration is a common problem. The aim of this study was to assess whether fibrin sealant applied to the duct incision is safe.
Methods:
Patients planned for laparoscopic gallstone surgery at the Department of Surgery, Enköping Hospital, were included in the study. In cases where perioperative cholangiography showed CBD stones, LCBDE was performed through a longitudinal incision in the CBD. Randomization between closure of the incision with polyglactin sutures or with fibrin sealant was performed. After all the stones had been removed and the incision closed according to the allocation, an abdominal drain was placed close to the incision. A T tube was placed in the CBD or a straight tube into cystic duct for eventual postoperative cholangiogram. The patient and the surgeon assessing the postoperative course were blinded to the randomized allocation.
Results:
Altogether 51 patients were included from December 2012 to July 2016. Mean operative time was 188 minutes in the fibrin sealant group and 214 minutes in the suture group (P = .159). There was no significant difference between groups in bile flow in the abdominal drainage tube or in the CBD drain during the three first postoperative days. The time to removal of the abdominal drain did not differ significantly between groups.
Conclusion:
Although the present study lacks the statistical power to prove a benefit from fibrin sealant, it indicates that closure of the incision may be an option to reduce the risk for leakage. Further studies are required to confirm this. The study was retrospectively registered on clinicaltrials.gov September 5, 2015 (NCT02545153)
Background
The introduction of laparoscopy has led to a substantial improvement in the outcome of surgery for gallstone disease. Laparoscopic cholecystectomy is now widely accepted as the gold standard for treatment of symptomatic cholelithiasis. However, between 5% and 11% of patients undergoing cholecystectomy for gallbladder stones also have common bile duct (CBD) stones.1,2 Whereas laparoscopic cholecystectomy is widely considered as a routine procedure, the approaches for managing CBD stones vary widely. Intraoperative cholangiotomy, cholangioscopy, and laparoscopic CBD exploration (LCBDE) are techniques that allow removal of stones from the CBD during the index procedure. In most cases, LCBDE is a safe procedure, although with some morbidity 3 and risk for complications, including bile duct lesions and bile leakage. The risk of bile leakage is reduced by suturing the incision. However, suturing is a traumatic approach and requires a highly skilled surgeon. Furthermore, suturing is a time-consuming procedure. Since it is performed in the close vicinity of the hepatoduodenal ligament, there is also a risk for vascular trauma and hemorrhage.
Bile leakage requiring postoperative intervention is seen after 1.1% of all cholecystectomies. 4 The risk of bile leakage is even greater in cases where CBDs are present, since they may cause obstruction and increased pressure within the bile ducts. Safe closure of the CBD incision is therefore crucial. When dissecting along the CBD before incision, the peritoneum is separated from the anterior surface of the CBD. To avoid postoperative bile leakage, a T-tube may be placed in the CBD. As the T-Tube diameter is smaller than the incision, the incision is closed around the tube.
Stricture of the common bile duct is also a feared complication of cholangiotomy. Suturing the CBD along the incision may result in the development of scar tissue that eventually results in narrowing of the bile duct and late stricture formation.
The aim of the present study was to assess whether application of fibrin sealant to the incision is a safe and effective alternative to suturing the incision after LCBDE.
Methods
Study design
From December 2012 to July 2016, we undertook a single-center randomized controlled, parallel-group, double-blind trial aimed at comparing closure of the CBD incision using fibrin sealant with suturing of the incision. The study is registered on clinicaltrials.gov (NCT02545153). The study was approved by the Ethics Review Board of Uppsala (2013/166).
Study participants and eligibility criteria
All patients scheduled for laparoscopic cholecystectomy at the Department of Surgery, Enköping Hospital, during the period of study were eligible for inclusion (Fig. 1). Written information about the study was sent by mail before the procedure. Verbal and written consent were obtained on the day of surgery.
Flow chart of study group enrollment process.
Procedures and intervention
The decision whether to use T-tube drainage was at the discretion of the surgeon performing the procedure. If a T-Tube was used, it was placed with one limb ∼1 cm proximally into the hepatic duct and the opposite limb ∼1.5 cm distally in the CBD. If the surgeon was completely convinced that the CBD had been cleared of all stones and that there was no sign of obstruction of the papilla Vateri, the incision was left without a T-Tube and a straight tube was inserted into the cystic duct for eventual postoperative cholangiogram.
Regardless of the randomization, a postoperative cholangiography was performed to ensure stone clearance. The T-tube was removed 10 days after the cholangiography. The abdominal drain was removed when the bile flow ceased, but not earlier than 3 days postoperatively.
The patients and the staff responsible for the postoperative care were blinded to the allocation. The blinding concerned the closure of the incision, but not to the management of the T-tube or any other procedures related to the postoperative care. Data in the case record form were registered by a physician or member of the staff that was blinded to the allocation.
Randomization
Randomization was performed during the procedure in cases where perioperative cholangiography showed one or more CBD stones requiring intervention. The randomization procedure was performed using a concealed envelope system without blocking. The surgeon and the staff in the operating theater were aware of the treatment allocation, but not the patient or the surgeons and staff responsible for postoperative care. If the patient was randomized to fibrin sealant closure, 1 mL of Tisseel® (Baxter) was applied on the incision. In case the patient was randomized to suturing, the incision was closed with interrupted Vicryl® 4.0 (polyglactin 910; Ethicon) sutures.
Outcomes
The primary outcome was the total amount of bile measured in the abdominal drain. Secondary outcomes were length of hospital stay, flow in the T-tube, time to removal of the abdominal drain, and postoperative complications.
Statistical analysis
Differences between the groups in terms of drainage flow, operating time, and time to removal of the abdominal drain were tested with Student's t test. The sample size estimation was based on the estimated number of procedures performed in Enköping each year, assuming that CBD exploration would be performed in 5% of the cholecystectomies. 3
Results
Altogether 51 patients were included. There were 26 patients allocated to the fibrin sealant closure group and 25 patients to the suture group. None of the patients had undergone magnetic resonance tomography of visualizing CBD stones before surgery, all CBD stones were detected intraoperatively by intraoperative cholangiography. Furthermore, no patients had undergone endoscopic retrograde cholangiopancreatography with sphincterotomy before the cholecystectomy.
There was no significant difference in history of cardiovascular disease, gender, or age between the two groups. Indication for surgery was also equally distributed between the groups.
Baseline characteristics are shown in Table 1. Mean operating time was 214 minutes (standard deviation [SD] 72 minutes) in the control group and 188 minutes (SD 55 minutes) in the fibrin sealant group (P = .157). Bile flows through the abdominal drain and T-tube are presented in Table 2. There was no statistically significant difference between groups in operating time, abdominal drain bile flow, or T-tube flow the first 3 days, although there was a tendency toward less flow in the fibrin sealant group. There was no major complication requiring reoperation, or cardiovascular event in either group.
Baseline Data
Outcomes Registered Before Discharge
At a 3-month follow-up, there was no statistically significant difference in complication rate between the groups (P = .30, Table 3). Time to removal of the abdominal drain did not differ significantly between the groups.
Complications Registered at Three-Month Follow-Up (P = .30)
Retained stones were confirmed at ERCP in 3/8 cases.
ALP, alkaline phosphatase; ERCP, endoscopic retrograde cholangiopancreatography.
In a retrospective review of the patient records undertaken in 2020, none of the patients had developed clinical signs of bile duct stricture or had undergone any intervention related to an assumed bile duct stricture.
Discussion
In the present study, we did not see any statistically significant difference between the two groups in terms of bile leakage from the CBD incision. There was, however, a tendency toward less flow in the abdominal drain in the fibrin sealant group. Although the present study lacks the statistical power to prove a benefit from fibrin sealant, it indicates that closure of the incision may be an option to reduce the risk for leakage.
Even if no difference was seen between the groups, there are advantages with fibrin sealant that are difficult to show in studies like the present one. Closing the incision with sutures requires advanced technical skill. Applying fibrin sealant, on the other hand, is rather straightforward and may easily be performed by most surgeons with basic experience in laparoscopic surgery.
Concerns have been raised regarding the fibrinolytic activity of human bile and the use of fibrin sealant in liver surgery. 5 Nevertheless, the present study does not indicate that the fibrinolytic effect of bile resulted in breakdown of the fibrin sealant. These results are in accordance with those of previous studies where fibrin sealant was used to prevent bile leakage following liver surgery.6–8 It also confirms the outcome of an animal study, where fibrin sealant was found to have a good biliostatic effect. 9
The present study has some limitations. Whether to place a T-tube or close the incision primarily was at the discretion of the surgeon. Although this may have increased the safety and resulted in a more adequate selection of patients likely to benefit from primary closure, it may also have caused some selection bias. Even if a T-tube was used in the vast majority of the procedures and there was no difference between the groups, this may have affected the outcome.
Due to the limited sample size, it is difficult to draw definite conclusions regarding the safety of fibrin sealant for prevention of bile leakage. Nevertheless, there was a tendency toward less bile leakage in the fibrin sealant group, suggesting that it is not inferior to suturing the incision.
In conclusion, fibrin sealant seems to be an alternative to suturing of the incision following LCBDE. Studies with greater power are required if we are to confirm this observation.
Ethics Approval and Consent to Participate
The study was approved by the Ethics Review Board of Uppsala (Regionala Etikprövningsnämnden i Uppsala, 2013/166). All participants gave written and verbal consent to the study before surgery.
Footnotes
Authors' Contributions
B.D. assembled the data and drafted the article. T.N. participated in the data assembling and interpretation of the data. G.S. designed the study and performed the analyses. All three authors have approved to the submitted article.
Disclosure Statement
No competing financial interests exist.
Funding Information
The study was supported by grants from the Bengt Ihre Research Foundation and Rickard and Rut Juhlin's Research Foundation. The grant number is 2020-00273.