Optimal timing of laparoscopic cholecystectomy post-endoscopic retrograde cholangiography and common bile duct clearance: A prospective observational study.

Background: The treatment of patients with cholelithiasis with common bile duct (CBD) stones is CBD clearance with cholecystectomy. While traditional teachings advocate waiting for 4-6-week post-endoscopic retrograde cholangiography (ERCP) with CBD clearance, recent studies favour an early laparoscopic cholecystectomy (LC). Hence, this study was conducted to evaluate the optimal timing of LC post-ERCP.
Methods: We conducted a prospective observational study between March 2017 and October 2018. Patients diagnosed with cholelithiasis and CBS stones on ultrasonography or computed tomography were included. They were assigned to one of two groups (<2 weeks and >2 weeks) based on the time interval between ERCP and subsequent LC. Chi-square test was used to analyse the intraoperative and post-operative outcomes between the two study groups.
Results: One hundred and forty patients were included in the study of which 69 underwent an early LC (<2 weeks). There was a significant decrease in the blood loss and incidence of bowel injury in the early group. Calots triangle was better defined and critical view of safety was achieved more in the patients who underwent an early LC. This resulted in a significantly lower incidence of drain placement and length of hospital stay in those patients who underwent an early LC.
Conclusion: A delay of 2 weeks after ERCP makes the LC more difficult and is associated with a longer hospital stay. We advocate LC within 2 weeks of ERCP whenever feasible.

INTRODUCTION

Common bile duct (CBD) stones coexist in around 10%–18% of patients with gall bladder stones.[1] Fifty per cent to fifty-five per cent of patients with CBD stones are symptomatic and around 25% of these suffer from complications of choledocholithiasis, with pancreatitis and cholangitis being the most dreaded ones.[2] The ultimate treatment involves CBD clearance with cholecystectomy.

Traditional teachings advocate waiting for 4–6-week post-Endoscopic retrograde cholangio pancreatography (ERCP). However, the use of contrast in ERCP elicits an inflammatory reaction around the CBD and sphincterotomy leads to bacterial colonisation of the CBD which causes inflammation and scarring of the hepatoduodenal ligament[3]. This leads to difficulty in performing laparoscopic cholecystectomy (LC) and studies have shown that LC following ERCP is more difficult.[456]

Hence, recent trend favours LC to be done early, within 72 hours of ERCP before the inflammation can render the calots triangle frozen.[2357] However, laparoscopic surgery in an acute setting may increase the chances of complications. This study was conducted to evaluate the best time for patients to undergo LC after ERCP. The time interval between the two procedures and the difficulty to perform LC, intraoperative blood loss, post-operative complications and post-operative hospitalisation was analysed. We present our experience of LC following ERCP in this study.

METHODS

Study design

We conducted a prospective observational study in the department of general surgery in a tertiary care setup between March 2017 and October 2018. Patients were admitted under the general surgery units and they underwent ERCP in the department of gastroenterology on inpatient basis. The study was approved by the institutional ethics committee.

Eligibility criteria

Patients with choledocholithiasis and cholelithiasis diagnosed on the basis of ultrasonography (US), contrast enhanced computed tomography (CECT) or an endoscopic US (EUS) were included in the study. Patients with complications during ERCP such as duodenal perforation and pancreatitis and those with failure of complete CBD clearance were excluded from the study. Patients with uncontrolled hypertension, uncontrolled diabetes and chronic renal disease or liver cirrhosis were also excluded from the study.

Group allocation

The patients with suspected choledocholithiasis with cholelithiasis were admitted in the department of general surgery. Diagnosis was confirmed with either an US, CECT or EUS. These patients were then referred for ERCP to the department of gastroenterology on inpatient basis. The ERCP was performed by a qualified gastroenterologist. After a successful ERCP with CBD clearance, the patients underwent LC in their respective surgical unit. The decision to perform LC within 2 weeks of ERCP or waiting for more than 2 weeks after ERCP was taken by a consultant of the respective surgical unit. The patients were operated on by general surgeons with at least 1 year of post-qualification experience. The patients were then assigned to one of two groups based on the time interval between ERCP and subsequent LC;

Early: LC done within 2 weeks of ERCP

Delayed: LC done after 2 weeks of ERCP.

Data collection

The records of ERCP were evaluated to find procedural data such as duration of ERCP, requirement of PD stenting and any complications. The operative notes were analysed for pertinent data of LC. Intraoperative difficulty to achieve critical view of safety, requirement of drain placement, bile spillage, bowel injury, requirement of a bail out procedure and other intraoperative details were noted. Serosal tears were considered as bowel injury. The post-operative length of hospital stay was considered for the purpose of this study. Readmissions were not included in calculating this length of hospital stay post-LC.

Follow-up

Patients were then observed during their routine follow-up to the operating surgeon on 7th, 14th, 28th day and 6-month post-surgery. Details regarding complications such as bile leak and surgical site infection (SSI) were noted.

Statistical analysis

Data were analysed by SPSS (the Statistical Package for the Social Sciences version 26; IBM; Chicago, IL, USA). Blood loss, a continuous variable, was represented as categorical data by considering groups of <50 ml blood loss and >50 ml blood loss during LC. A Chi-square test was used to determine statistical significance for categorical data and the unpaired t test was used for continuous variables. Statistical significance was set at 0.05.

RESULTS

A total of 144 patients met the inclusion criteria for this study. Four patients from this cohort suffered from complications of ERCP or had an unsuccessful CBD clearance and were excluded from the analysis. Out of these 140 patients, 69 patients underwent an early LC (within 2 weeks of ERCP) while 71 patients underwent a delayed LC [Figure 1].

Figure 1

Recruitment algorithm

In our study, the mean age of patients was 41 years and there was a slight female preponderance seen (59.3%). Multiple gall stones were observed in 55% of the cases [Table 1]. All the patients were non-icteric and had normal or mildly elevated liver enzymes (mean 54 U/L). The laboratory parameters of the present cohort are shown in Table 2. Both the study groups were homogenous in terms of patient demographics and investigations as illustrated in Tables 1 and 2.

Table 1

Patient profile

	Early LC (n=69), n (%)	Delayed LC (n=71), n (%)	P
Sex
Male	27 (39)	30 (42)	0.565
Female	42 (61)	41 (58)	0.573
Age (years)	39±7.5	45±8.9	0.877
Gall bladder stone
Single	34 (49)	28 (39)	0.433
Multiple	35 (51)	43 (61)	0.643

Values are listed as either n (%) or mean±SD. LC: Laparoscopic cholecystectomy, SD: Standard deviation

Table 2

Investigations

	Early LC (n=69)	Delayed LC (n=71)	P
CBD diameter (mm)	7 (6-8)	7 (6-8)	0.996
ALT (U/L)	58 (46-67)	59 (44-68)	0.877
AST (U/L)	52 (40-62)	54 (45-70)	0.643
ALP (U/L)	146 (122-164)	156 (129-167)	0.823
Total bilirubin (mg/dL)	1.1 (1.1-1.5)	1.3 (1.2-1.6)	0.627
Direct bilirubin (mg/dL)	0.3 (0.2-0.4)	0.3 (0.1-0.4)	0.994

Values are listed as median (IQR). CBD: Common bile duct, ALT: Alanine transaminase, AST: Aspartate transaminase, ALP: Alkaline phosphatase, LC: Laparoscopic cholecystectomy, IQR: Interquartile range

The diameter of CBD was similar in size on US and CECT (mean diameter 7 mm). Alkaline phosphatase was within normal limits (median value 165).

The mean duration of ERCP was 45 min, with complete clearance being achieved in all but 2 cases in the first attempt. Inadvertent pancreatic duct (PD) cannulation requiring placement of a PD stent was seen in 14 (10%) cases.

Sixty-nine (49%) cases underwent LC <2 weeks from ERCP. The median duration of surgery was 45 min. In this study, bowel injury during LC was noted in 5 (3%) cases while bile spillage was seen in 11 (7.9%) cases. We were able to dissect the calots triangle safely in 84 (60%) cases to achieve the critical view of safety. We were forced to convert to open surgery in 8 (5.7%) cases and bile leak in the post-operative period was also noted in 8 (5.7%) cases. There was a 8.6% incidence of a SSI in the present study [Tables 3 and 4].

Table 3

Data pertaining to endoscopic retrograde cholangiopancreatography, laparoscopic cholecystectomy and overall post-operative outcome

Operative and Post Operative Data	(n=140)
Total patients	140
Duration of ERCP (min)	45 (45-60)
CBD clearance (%)	140 (100)
Unsuccessful attempts (2 attempts in one patient) (%)	8 (5.7)
PD stenting (%)	14 (10)
Time interval between ERCP and LC	14 (1-58)
Duration of LC (min)	45 (20-100)
Mortality	-
Length of post-operative hospital stay (days)	3 (2-15)

Values are listed as either n (%), median (range). ERCP: Endoscopic retrograde cholangiopancreatography, CBD: Common bile duct, PD: Pancreatic duct, LC: Laparoscopic cholecystectomy

Table 4

Comparison of intraoperative findings, complications and post-operative outcomes between the two groups

	Total (n=140), n (%)	Early LC (n=69)	Delayed LC (n=71)	P
Blood loss <50 ml	118 (84.2)	104	14	<0.001
Bile spillage (n)	11 (7.9)	4	7	0.372
Bowel injury (n)	5 (3.6)	0	5	0.025
Frozen calots triangle (n)	69 (49.3)	9	60	<0.001
Critical view of safety achieved (n)	84 (60)	53	31	<0.001
Adhesions (n)	63 (45)	15	48	<0.001
Drain (n)	85 (60.7)	28	58	<0.001
Conversion to open (n)	8 (5.7)	2	6	0.157
Bile leak (n)	8 (5.7)	3	5	0.492
SSI (n)	12 (8.6)	3	9	0.078
Mean length of post-operative hospital stay (days) (n)	4.3	3.1	5.4	<0.001
Readmissions (n)	7 (5)	2	5	0.261

SSI: Surgical site infection

Seven (5%) the cases required readmission for a delayed complication. The average length of post-operative hospital stay was 4 days. No mortality was noted in the present study [Table 3].

Out of the 140 cases, 69 cases underwent an early LC. There was a significant decrease in the blood loss for this cohort (P < 0.001). Chance of bowel injury was also significantly lower (P = 0.025). We were better able to define the calots triangle and achieve the critical view of safety (P < 0.001) in the patients who underwent an early LC since there was lesser periportal inflammation and fewer adhesions (P < 0.001) were present. This resulted in a significantly lower incidence of drain placement for this group (P < 0.001). Length of hospital stay was also lower in those patients who underwent an early LC [Table 4].

DISCUSSION

Management of choledocholithiasis with cholelithiasis necessitates clearance of CBD and cholecystectomy to eliminate the source of gall stones. Approaches vary with experience and expertise and include laparoscopic CBD exploration, open CBD exploration and various sequences of LC and ERCP.[2] Open CBD exploration carries significant morbidity to the patient and is not popular in the present scenario. Laparoscopic CBD exploration with cholecystectomy is an attractive alternative, but this is a challenging procedure with a steep learning curve. Lack of expertise limits this option to only advanced laparoscopic centres. Endoscopic sphincterotomy through ERCP with stone extraction has therefore gained wide acceptance with studies reporting a success rate of more than 90%.[8] Performing a LC first followed by ERCP seems excellent to avoid unnecessary ERCP's but if post-operative ERCP fails or there is some complication (a 4% risk), the patient may require a second surgical procedure.[2] Intra-operative ERCP is a single-stage procedure, but feasibility limits its use. Hence, pre-operative ERCP is most commonly used for clearing the CBD in patients with choledocholithiasis with cholelithiasis. There still exists considerable debate between the timing of LC after ERCP.

In this study, we evaluated the intra-operative difficulties faced during LC and the outcomes of LC when performed within 2 weeks and after 2 weeks of ERCP. In our study, we were able to delineate the triangle of safety in significantly more patients when they were operated within 2 weeks of ERCP (P < 0.05). There was significantly less peri-portal inflammation and calots triangle was not frozen when LC was performed early. This is in agreement to other studies which advocate early LC following ERCP.[23910] Zhang et al. collected data of 105 patients and showed that the mean duration of surgery and the intraoperative blood loss was the highest when the patients underwent LC within 4–6 days of ERCP.[3] Salman et al. grouped patients as those operated on between 24 and 72 h after ERCP (n = 39) and those operated on more than 72 h after ERCP (n = 40). They showed that median operation time, median post-operative hospital stay and conversion rate in Group 2 were significantly higher than those of group 1 and more post-operative complications were seen in Group 2.[2] The likely explanation is that local inflammation ensues because of endoscopic sphincterotomy and contrast agents.[3] Kilciler et al. and Chen et al. demonstrated an early increase (within 24 h) in the serum interleukin (IL)-2, IL-4, tumour necrosis factor a and IL 6 levels post-ERCP irrespective for the development of post-ERCP pancreatitis.[1112] These findings showed that an acute inflammation process starts early after ERCP. This local inflammation leads to poor vision, formation of friable granulation tissue which bleeds easily and hence makes the surgery difficult. This may also explain the higher blood loss noted in the delayed LC group in the present study a finding which is consistent with that noted by Zhang et al.[3]

As fibrosis progresses in the inflammatory process, local adhesions may alter the biliary anatomy and create a pull on the CBD causing it to be misidentified as the cystic duct. Dense adhesions in Calot's triangle may render it impossible for laparoscopic dissection. A frozen calots was responsible for the higher rate of bail-out procedures in delayed group of this study. This also led us to insert a drain in significantly more patients undergoing a delayed LC (P < 0.05). Perioperative complications such as CBD injury and bile leak were seen in both the early and the groups with delay between ERCP and LC. In agreement to the results of Bostanci et al., we also did not find a statistically significant increase in the rate of CBD injury or bile spillage in this study.[5] However, we did note a significantly higher incidence of bowel injury in the delayed group (0 vs. 5 cases) a finding which is not reported previously. However, further studies with a larger sample size are required to confirm this finding.

There was a significantly longer duration of post-operative hospital stay (3 vs. 5 days) when patients were operated after 2 weeks. A similar finding was published by Borreca et al. and 2 other studies.[11314] Borreca et al. divided patients into three groups. In the first group, surgery was performed on the same day of ERCP (n = 36), in Group 2, surgery was performed within 72 h of ERCP (n = 29) and in the third group, the surgery was delayed (n = 28). They showed that length of stay was least in the group where surgery was performed on the same day of ERCP and was highest in the delayed group.[13] The reason for a longer hospital stay was a higher rate of conversion to open in the second group in all the studies. We also report a higher rate of conversion to open in the delayed surgery group, though the result is not statistically significant.

The strength of our study lies in the completeness of its data. There were no missing variables in this data set. A smaller sample size and lack of randomisation are limitations of this study and we advocate studies with a larger sample size to confirm the our findings.

CONCLUSION

A delay of 2 weeks after ERCP makes the LC more difficult and is associated with higher intraoperative blood loss and a longer post-operative hospital stay. Since delineating the critical view of safety was easier, less patients required placement of a drain and there was a reduced incidence of bowel injury in Group 1; we advocate performing LC within 2 weeks of ERCP whenever feasible.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.