The preventive effect of medical biological glue on postoperative bile leakage in laparoscopic common bile duct primary suture

doi:10.21203/rs.3.rs-4983803/v1

Aim

Laparoscopic common bile duct exploration for stone removal is a relatively comfortable procedure for patients, but the risk of bile leakage after surgery is still a concern. However, the use of medical biological glue in small incisions of the common bile duct may offer a solution. The effectiveness of this method for reducing the occurrence of bile leakage is still uncertain, but it holds great potential for improving patient outcomes. At Juxian People's Hospital, we are committed to exploring all options for enhancing the safety and comfort of our patients.

Objective

To evaluate the value of medical biological glue in preventing biliary fistula in laparoscopic choledochotomy in patients with non-acute suppurative cholangitis.

Methods

Patients undergoing laparoscopic choledochotomy and primary suture were divided into two groups: the control group (group 2 n=24) underwent continuous suture with absorbable sutures, and the experimental group (group 1 n=18) underwent continuous suture with absorbable sutures followed by spraying of medical biological glue. The incidence of biliary fistula, removal time, discharge time, and other indicators were compared between the two groups.

Results

The incidence of biliary fistula, amount of biliary leakage, postoperative hospital stay, and postoperative cost were significantly lower in the biological glue group than in the control group. The use of biological medical glue did not cause any relevant complications, did not affect liver function, did not delay intestinal exhaust time, and the patients felt good overall.

Conclusion

Medical biological glue can significantly reduce the incidence of biliary fistula after laparoscopic choledochotomy and primary suture, without increasing additional complications.

Biliary fistula

Choledocholithiasis

Choledochotomy and primary suture

Medical biological glue.

After the laparoscopic choledocholithotomy and primary closure, the problem of bile leak has not been resolved. This study cleverly uses medical bio-glue after primary closure, which can greatly reduce the probability of bile leakage and the volume of leaked bile.
The use of medical bio-glue has been proven to be safe in clinical practice and does not increase the incidence of adverse reactions. It is well tolerated by the human body, and its use does not increase hospitalization costs.

Preoperative and intraoperative assessment of patients with suitable conditions of common bile duct, undergoing laparoscopic common bile duct incision and stone removal followed by primary closure, is considered a safe surgical procedure. However, some surgeons refuse to perform primary closure of the common bile duct due to concerns about postoperative bile leak. Of course, if the common bile duct is forcefully closed in case of incorrect assessment of the bile duct condition, it can also cause problems with postoperative bile leak. Currently, there is limited data on the use of medical adhesive in common bile duct primary closure surgery and it is unclear whether it can reduce the incidence of postoperative bile leak. The main purpose of this literature study is to evaluate the value of using medical biological glue in primary closure of the bile duct.

In this study, we selected patients who underwent laparoscopic common bile duct exploration with primary closure from January 2023 to January 2024. A total of 42 patients were included in the data analysis, and all patient data were obtained from the People's Hospital of Juxian County, Shandong Province. They were divided into two groups: one group was treated with continuous suturing and spraying of medical biogel (n = 18), while the other group was treated with simple continuous suturing without biogel (n = 24). All patients underwent nutritional risk assessment, infection indicator assessment, assessment of cardiac, pulmonary, renal, and intestinal function, especially liver function assessment, thrombosis and bleeding assessment, and liver and bile duct imaging assessment, mainly using magnetic resonance imaging, with computed tomography as a secondary option.

Patients with acute pancreatitis, intrahepatic bile duct stones, transabdominal transfer, or incomplete data were excluded from the study.

This research protocol was approved by the Ethics Committee of the People's Hospital of Juxian County, Qingdao University Medical Group. All patients received general anesthesia. The operation was performed using the four-hole method, with the Olympus laparoscope system, Olympus choledochoscope, and one-time stone removal basket. The gallbladder was retrogradely freed, and the lateral side of the common bile duct that needs to be incised was exposed before gallbladder removal. The free surface of the common bile duct should be as narrow as possible to avoid the influence of blood supply to the common bile duct. The opening of the common bile duct is generally selected at the widest diameter of the common bile duct and usually centered on the junction of the cystic duct and the hepatic duct. An Olympus 5mm choledochoscope was used to enter the common bile duct from the trocar under the xiphoid process, and sometimes a trocar under the right clavicle midline and rib margin was also used. The biliary tract was washed with warm saline, and one-time stone removal basket was used. If the stone was impacted, liquid electric fragmentation or holmium laser-assisted fragmentation could be used.

After the stone removal, the course of the common bile duct, whether there is any tortuosity, intestinal fluid reflux, Oddi sphincter function, and especially the inflammation of the common bile duct mucosa, needs to be evaluated. If the inflammation of the common bile duct is obvious, it is recommended to place a T-tube drainage tube. The common bile duct sutures were made using 4 − 0 or 5 − 0 micro-bridging wires (depending on the thickness of the common bile duct wall), with continuous sutures. Firstly, an 8-shaped suture knot was made, followed by continuous suturing, and finally an 8-shaped suture knot was made at the end. The suture margin should not exceed 2-3mm, and the needle distance should be about 3–4 times the thickness of the common bile duct wall. Patients who signed a consent form for the use of medical biogel were sprayed with biogel on the common bile duct incision site (mix the biogel immediately before use). The winslow hole was placed in advance, the assistant fully exposed the operation field, paid attention to not applying too much tension on the bile duct suture, sucked the surrounding fluid, kept the common bile duct wound as clean as possible, and quickly sprayed the biogel, generally 2–3 times, to quickly solidify within 5 seconds. Then, the drainage tube was quickly and slightly pulled to avoid the drainage tube being fixed by the biogel, resulting in too much resistance when pulling out the tube. On the second day after the operation, the drainage tube was withdrawn by 1-2cm. If there was no bile leakage, the tube was generally removed on the third day. If there was bile leakage, the drainage tube was removed on the second day after the bile leakage stopped, and the removal time was appropriately prolonged for some patients. If the drainage volume was large or if there was obstructive jaundice and the decrease in bilirubin was not obvious, abdominal CT examination was required to determine whether there was poor drainage or significant fluid accumulation around the liver before deciding whether to remove the tube.

The evaluation indicators included the operation time, postoperative bilirubin concentration, recovery of transaminase, postoperative albumin level, incidence of bile leakage, common bile duct stenosis, length of hospital stay, hospitalization costs, and allergic reactions.

Data analysis

Chi-square test was used for gender analysis; multivariate analysis was used for the analysis of age, liver function, albumin and other basic data on postoperative drainage volume; generalized linear model analysis was used for the analysis of multivariate variables between the two groups for daily drainage volume, Biliary leakage and extubation days.

The use of medical biological glue in bile leakage led to a lower proportion of bile leakage, less volume of bile leakage(Table 2), shorter time to remove the drainage tube, and shorter hospital stay, all of which were better than those without the use of the glue. There was no difference in postoperative bilirubin concentration, transaminase level, and postoperative albumin level between the two groups There was no significant difference in the recovery level of prothrombin activity or serum bilirubin levels between the two groups. No stone recurrence was found in the common bile duct within three months in both groups. None of the patients experienced acute suppurative obstructive cholangitis or acute pancreatitis. One case of pleural effusion occurred in the bio-glue group, while three cases of pleural effusion occurred in the control group. This may be due to older age, general cardiopulmonary function, and hypoproteinemia（Table 1）. Currently, all patients have been followed up for more than three months after the outpatient review one month after surgery, and follow-up will continue for one year.

Drainage volume(Table 2): After bile leakage occurred in the bio-glue group, the drainage volume was relatively low; in the control group (conventional primary suture), the daily drainage volume was relatively high, and the drainage duration was longer, especially from the second to the fifth day (P <0.05). Postoperative bio-glue did not cause any related complications.

Table 1 Comparison of patients' general data

	Group 2	Group1	P值
Sex（man，women）			0.859
age	68.18 ± 3.18	65.00±3.03	0.374
CBD diameter(cm)	1.48±0.13	1.58±0.42	0.818
Bile duct thickness (mm)	3.82±0.72	3.76±0.83	0.8
ALB	40.33±2.89	39.08±5.58	0.347
ALT	160.58±98.03	139.05±125.83	0.503
AST	150.41±92.23	123.66±162.09	0.542
GGT	339.65±295.93	354.68±332.93	0.8815
bilirubin	55.612±39.57	46.62±34.70	0.44
Prothrombin	75.08±10.50	81.60±23.38	0.289
PS score	4.76±0.44	4.96±0.20	0.099

Biogel group = biological glue group(group 1 )

No-Biogel group = no-biological glue group(group 2 )

There was no significant difference in general data between the two groups.

Table 2 Comparison of postoperative drainage volume between two groups

1day= the first day 2 day=the second day 3 day=the third day

Table 3 Biliary leakage and Extubation days

			P
	Biogel group	0.88±1.45	0.001
Bile leakage days
	No Biogel group	2.04±1.54
Extubation days	Biogel group	3.11±1.32	0
	No Biogel group	5.24±1.42

In terms of bile leakage(Table 2\Figure 2\ Figure 3): the use of medical biological glue significantly reduced the amount of bile leakage (Table 2). Bile leakage occurred in 5 out of 18 cases using the biological glue group, while it occurred in 18 out of 24 cases in the non-use group (P < 0.05 Figure 2). The use of biological glue reduces the days of bile leakage significantly (Figure 3).

The extubation time: in the biological glue group was 3 days (P < 0.05 Figure 1), and the hospital stay was shortened by 3 days (P < 0.05). Even if bile leakage occurred after surgery in the biological glue group, the amount of bile leakage was relatively less, and the extubation time was relatively shorter（p<0.05）. One case of bile duct stenosis occurred in a patient who did not use medical biological glue, but the condition improved after conservative treatment, possibly due to uneven tension during suturing.

There are two main surgical methods for patients with gallbladder stones and bile duct stones^[1–4]: (1) laparoscopic primary closure of the bile duct + cholecystectomy ,LCBDE(with or without insertion of endobiliary stent^[3])and (2) ERCP for bile duct stone removal + laparoscopic cholecystectomy (if there is a hybrid operating room, it can be performed at the same time, and if not, it can be staged). However, the risk of damage to the sphincter of Oddi^[3] after ERCP has always existed, which can cause dysfunction of the sphincter of Oddi, reflux cholangitis, stone recurrence, and stenosis of the lower biliary tract. Therefore, some experts are increasingly paying attention to the laparoscopic primary closure of the bile duct technique^[5].

If it is not possible to perform hybrid surgery, LC surgery may need to be performed, which may increase surgical costs and risks. Laparoscopic primary closure of the bile duct incision for stone removal and cholecystectomy is a safe and efficient method[^{5, 6]}.

However, patients who undergo bile duct stone removal (primary closure) commonly experience bile leakage, which is the most urgent problem to be solved^[7]. Appropriate methods can reduce the occurrence of bile leakage, such as improving the patient's nutritional level: using albumin or intravenous nutrition in a timely manner, using drugs: cholangitis drugs, choleretic drugs, and liver function-improving drugs. In particular, strict training in laparoscopic surgery is required^[8]. Of course, the improvement of laparoscopic suturing technology can reduce bile leakage to a certain extent, but after a large amount of data research, no method has been found that can completely prevent postoperative bile leakage^[9].

The use of biological glue is also related to postoperative bile leakage, and so far, no relevant complications have been found with the biological glue we use^[10]. However, there are risks, such as whether the biological glue will enter the bile duct and form new foreign bodies, leading to stone recurrence or cholangitis. The biological glue has not been found to cause intestinal obstruction recently, but whether it will increase the occurrence of intestinal obstruction in the long term needs further observation.

The following is our team's experience in the use of biogel in the first stage of common bile duct suture: When using it, a certain amount of exploration is needed. We usually place the drainage tube first, suck out the surrounding liquid, remove the gauze strip, fully expose the sutured bile duct, and then spray the glue. The key points of processing are: first, fully exposing the bile duct; second, keeping the appropriate tension of the bile duct wall, which should be given mild tension, which requires some experience to accumulate; third, not emptying the air in advance, should be aimed at the bile duct incision, about 3cm away, quickly injecting air and glue, and the appropriate injection distance can make the glue injection uniform. We look forward to the development of more advanced medical biological glue suitable for bile duct incisions in the future^[10].

There are several issues that need to be explained separately in this article[11]. First, from the perspective of surgical techniques and methods alone, biological glue can be tried to reduce the occurrence of bile leakage. Second, because the time occupied by the biological glue is very short, averaging 3–5 minutes, the issue of surgical time has not been discussed. The cost of biological glue is very small in the total cost, and it clearly shortens the extubation time and reduces hospital stay, so the actual total cost of the biological glue group is less than the control group. Third, the length of hospital stay after surgery mainly depends on whether there are complications and extubation time. Fourth, the diagnostic criteria for bile leakage: bile is continuously drained for three days or the single drainage volume of bile is ≥ 100ml, but in reality, because physiological saline is used for flushing during the intraoperative cholangioscopy. It is difficult to define whether there is bile leakage from the ^drainage volume on the first day after surgery. The color of the drainage fluid should also be observed. When it is unclear whether the fluid is bile, the concentration of bilirubin in the drainage fluid should be measured to determine whether there is bile leakage^[12]. Fifth, the follow-up time of this article is all over three months, and no relevant complications related to the use of biological glue during hospitalization have been found in the biological glue group^[11]. This study is only a study of a center in the hepatobiliary pancreatic spleen surgery department of this hospital, with a small sample size and a not long enough follow-up time. Further increase in sample size and follow-up time is needed.

This study confirms that the use of biological materials in laparoscopic primary closure of the common bile duct can reduce the incidence and volume of bile leakage, shorten hospital stay, and increase patient comfort by reducing the duration of drainage tube place-ment, without causing any related complications.

Funding

This research was supported by the National Natural Science Foundation of China, with grants awarded to Lantian Tian (Code: 8207112292)

Author contributions

Lantian Tian: Resources, modify the article, Funding acquisition; Liqiang Mi: Methodology, Analysis, Writing—Original Draft; Jingxiang Li: Data collection and sorting，Outpatient review and Patient follow-up; Wenxin Wei Paper writing gives unique suggestions; Leitao Zhao 、Guangjian Yu、Yingrong Guo: Outpatient review and Patient follow-up.

Acknowledgments

Declaration of competing interest

All authors declare no conflicts of interest.

Data available

The data that support the findings of this study are available on request from the corresponding author(Liqiang Mi )( The data are not publicly available due to privacy or ethical restrictions.

Ethics statement

This study was approved by the Ethics Committee of The People's Hospital of Ju xian County, Qingdao University Medical Group ，Shandong Province and performed in accordance with the principles of the Helsinki Declaration.

Informed consent

All patients provided written informed consent at the time of entering this study.

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No competing interests reported.

The preventive effect of medical biological glue on postoperative bile leakage in laparoscopic common bile duct primary suture

Status:

Version 1

Abstract

Figures

Highlights

Background

Grouping and Method

Data analysis

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

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