|Year : 2020 | Volume
| Issue : 2 | Page : 659-664
Role of early endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis
Hatem M Sultan1, Ahmed G El Tatawy1, Mohamed A Mohamed2
1 Department of General Surgery, Menoufia University Hospital, Menoufia, Egypt
2 Department of General Surgery, Ras Eltin Hospital, Alexandria, Egypt
|Date of Submission||02-Jan-2020|
|Date of Decision||25-Feb-2020|
|Date of Acceptance||27-Feb-2020|
|Date of Web Publication||27-Jun-2020|
Mohamed A Mohamed
Source of Support: None, Conflict of Interest: None
The aim was to evaluate the role of early endoscopic retrograde cholangiopancreatography (ERCP) in reducing mortality and morbidity of acute biliary pancreatitis with the consideration of the economic burden of this maneuver.
A stone that obstructs the ampulla of Vater can cause biliary pancreatitis. ERCP is used to remove the stones that obstruct the ampulla. The risk-to-benefit ratio of this in the setting of acute pancreatitis is a matter of debate. In this research, we intend to overweight one of the both schools (conservative vs early ERCP).
Patients and methods
This prospective randomized comparative study was done at the Menoufia University Hospital between April 2015 and January 2018 which included 40 patients who were divided into two groups: groups A included 20 patients managed by early ERCP. Group B included 20 patients managed initially conservatively and they will be divided into three subgroups according to the course of jaundice. B1 subgroup: Those who will continue the conservative course due to continuous daily serial declination of their direct serum bilirubin. Group B2: those with continuous daily serial rising of the serum bilirubin (for 2 consecutive days) and they will be subjected to urgent ERCP. Group B3: those with fluctuating levels of serum bilirubin and they will be subjected to elective ERCP. Both group A and B patients will be subjected to laparoscopic cholecystectomy and were compared as regards the complications, mortality, economic burden, and hospital admission time.
There was only one complication in group A with a percentage of 5% while there were three complications in group B and there were three with a percentage of 15%; thus, there was a significant reduction in complications in group A (P 0=0.05–0.001).
Early ERCP by a well-trained endoscopist in acute biliary pancreatitis is effective in reducing the complications and hospital admission time though it has more cost.
Keywords: complications, conservatism, economic burden, hospital admission mortality, morbidity
|How to cite this article:|
Sultan HM, El Tatawy AG, Mohamed MA. Role of early endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis. Menoufia Med J 2020;33:659-64
|How to cite this URL:|
Sultan HM, El Tatawy AG, Mohamed MA. Role of early endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis. Menoufia Med J [serial online] 2020 [cited 2020 Oct 24];33:659-64. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/659/287800
| Introduction|| |
Acute pancreatitis (acute inflammation of the pancreas) is one of the major causes of gastrointestinal admission in hospitals. Its annual incidence ranges from 4.5 to 35 per 100 000 in USA. The overall mortality of acute pancreatitis ranges from 1 to 2% but in severe form it is much higher. In 25% of cases of acute pancreatitis it is severe and is associated with complications like respiratory or renal failure or fluid collection and these patients will need more care with prolonged hospital admission. The overall pancreatitis incidence in UK is 56 per 100 000 which means that there is 9310 patients nearly facing this risk in UK and the number is higher in Egypt due to the higher percentage of biliary pancreatitis to overall cases of acute pancreatitis in Egypt. Thus, if we prevent the progression of pancreatitis from mild to severe, we will gain a dramatic reduction in complications of acute pancreatitis with amazing improvement in the outcome of such cases. This is the aim of our early intervention by endoscopic retrograde cholangiopancreatography (ERCP). Biliary pancreatitis commonly account for 35–65% of cases of acute pancreatitis. It occurs when a gallstone is passing into the bile duct and temporarily loading at the sphincter of Oddi. The co-localization theory by union between zymogen and lysozyme granules is commonly accepted as a triggering event of pancreatitis, while an increase in intracellular calcium has recently proved to have a pivotal role in pancreatitis. In most cases, usually accounting to 85% of cases, the stone passes spontaneously while in the rest it remains impacted for more than 48 h. Those cases will be at high risk of progressing to severe pancreatitis.
The time lapse of stone impaction at the sphincter of Oddi is of great importance in determining the severity of pancreatitis. This is clarified by the low incidence of severe pancreatitis if the stone was impacted less than 24 h, meanwhile the incidence of severe pancreatitis rises significantly if the stone is impacted for more than 48 h. About half of the deaths in acute pancreatitis occurs in the first week due to multiorgan failure, while the other half occurs much later not due to multiorgan failure but also but due to infectious complications. On the other hand, pancreatitis has its local complications that are usually delayed such as abscess, psuedopancreatic cysts and walled-off pancreatic necrosis. ERCP is used to remove the stones from the ampulla by many methods such as using a balloon or basket, but has its own complications such as perforation, bleeding, infection, basket entrapment, and most importantly pancreatitis perse. There were many studies done to answer a logical question which is: Does early intervention by early ERCP affect the progression of the pancreatitis from mild to severe one? A study conducted in the UK made by Neoptolemus on patients with mild pancreatitis expected to have severe one by modified Glasgow criteria concluded that there were significant differences in morbidity in those subjected to early ERCP while mortality incidence did not differ significantly. While other studies neglect any benefit of ERCP in the absence of cholangitis. Thus the role of ERCP in acute biliary pancreatitis in the absence of cholangitis is still controversial. The aim of this study was to evaluate the role of ERCP in the management of acute biliary pancreatitis. In this study, we aim to overweight which of the two protocols (conservative vs early ERCP in the absence of cholangitis) is more beneficial in acute biliary pancreatitis based on the mortality and morbidity of patients with pancreatitis in such a protocol. There were three important lessons learned from this study: The first is that if we preclude elective ERCP in biliary pancreatitis, for fear of negative cases the number of cases shifted to ERCP in the conservative limp will exceed them. The second is the dependence on the scoring system for the selection of patients subjected to ERCP has its own limitations leading to missing of some cases that progressed to severe one and the third is that restriction of omens of ERCP in biliary pancreatic patient to cholangitis is not correct.
| Patients and Methods|| |
A prospective comparative randomized (by closed-envelope technique) controlled study was done at the Menoufia University Hospital between April 2015 and January 2018 which included 40 patients who were divided into two groups: Group A included 20 patients who will be managed initially with ERCP with concomitant laparoscopic cholecystectomy. Group B also included 20 patients who will be managed initially conservatively and will be subdivided into three subcategories according to the course of their jaundice: B1 subgroup: Those who will continue the conservative course due to continuous daily serial declination of their direct serum bilirubin. B2: those with continuous daily serial rising of the serum bilirubin (for 2 consecutive days) most probably due to impacted stone and they will be subjected to urgent ERCP. B3: those with fluctuating levels of serum bilirubin although pancreatitis may improve clinically (most probably due to floating stone or they may be stone passers) and they will be subjected to elective ERCP. Both group A and B patients will be subjected to concomitant laparoscopic cholecystectomy with their ERCP or laparoscopic cholecystectomy alone if they had successive conservative course. A written consent was taken from the patients about the procedures that will be done and investigations by the author was approved by the Local Ethics Committee. Both group B1 and B3 patients will be subjected to elective MRCP to preclude the presence of floating stone in B1 and passage of the floating stone in B3. The inclusion criteria were: those with pancreatitis diagnosed by high serum lipase and amylase and radiologically by computed tomography. Pancreatitis proved to be biliary by high serum bilirubin and alkaline phosphatase and alanine aminotransferase and dilated common bile duct by ultrasound. The exclusion criteria were: first, those proved to have non-biliary pancreatitis by normal CBD diameter on ultrasound; second, those who were unfit for general anesthesia; third, those admitted to the ICU; and fourth, those with coagulopathy. Four patients were excluded due to normal CBD diameter and normal serum bilirubin at the time of the attack of pancreatitis that precludes biliary etiology and this was confirmed by MRCP that excludes the presence of any stones or mud at the CBD. The economic, clinical, and humanistic outcome measures (ECHO) model was used.
ERCP technique: first, the patient was given general anesthesia in the supine position and then turned to prone position where the duodenoscope is inserted till it reaches the second part of the duodenum and the major duodenal papilla is identified. Second, a cannula is inserted inside the major duodenal papilla and dye is injected inside the cannula and a screenshot is taken by the C-arm to be sure that we are inside the CBD not the pancreatic duct. NB, if we fail in cannulation, we use the Rendezvous technique by performing laparoscopic cholecystectomy and then inserting a guidewire through the cystic duct till it reaches the duodenum via the ampulla, then a cannula reaches the duodenum by the duodenoscope and passes over the guidewire till it gets inside the ampulla. Third, we insert a guidewire inside the cannula, then remove the cannula and insert the sphincterotome over the guidewire where sphincterotomy is done by the tip of the sphincterotome from 11 o'clock till the supraduodenal fold. Fourth, then exchange process is done by removing the sphincterotome and inserting the balloon over the guidewire till the CBD carina and then trawling is done to remove the stones and mud till the bile gushes from the ampulla and if balloon failed we use a basket instead and if we fail in stone extraction due to large stones we shift to laparoscopic cholodochotomy. Fifth, we perform laparoscopic cholecystectomy after the ERCP.
Follow up: all the patients are asked to come to the university hospital every 2 weeks for 3 months to detect any delayed complication of pancreatitis
The study questions were: first, what was the percentage of negative cases for stones in the early ERCP limp of the study. Second, what was the percentage of successful initial cannulation in this limp and how many iatrogenic complications occurred in this limp. Third, what was the percentage of the cases of conservative limb of the study who were managed by ERCP and finally what was the percentage of the cases who continue conservatism. Fourth, how many cases in each group progressed to severe pancreatitis. Fifth, how many cases suffered from delayed complications in each limb. Sixth, what was the mean hospital admission time in each limp. Seventh, what was the economic burden in each limp and lastly what was the mortality in each limp.
Outcomes were obtained, tabularized, and analyzed statistically using an IBM personal computer with SPSS (version 22; SPSS Inc., Chicago, Illinois, USA), in which data were introduced as mean, SD, range, and in the form of numbers and percentage in the following table.
| Results|| |
In group A, there was successful initial cannulation of 19 of the 20 patients with a percentage of 95% and the remaining patients were successfully cannulated by the Rendezvous technique.
Stones were extracted from 12 of the 20 patients (11 of them were by ERCP and one by laparoscopic cholodocotomy due to its large size 1.6 cm); thus, there were eight negative cases for stones [Table 1]. The overall success percentage for stone extraction by ERCP equaled 11/12 with 93% success percentage. The size of the stones extracted is summarized in [Table 2]. In group B, 11 patients continued the conservative course (B1) by 55% and they were subjected to elective laparoscopic cholecystectomy (and two of them were subjected to ERCP due to the presence of floating stones revealed by MRCP) and four patients of group B had impacted stone and were subjected to urgent ERCP with concomitant laparoscopic cholecystectomy (B2) with a percentage of 20% and five had fluctuating bilirubin though the pancreatitis had improved (stone passers or had floating stone) (B3) with a percentage of 25% and they were subjected to elective ERCP with concomitant laparoscopic cholecystectomy [Figure 1]. It is an important notice that the percentage of cases that were converted to ERCP in the conservative limp was 45% which is slightly higher than the percentage of negative cases in early ERCP group [Table 3] One case of group B2 progressed to severe pancreatitis on the fourth day though his Glasgow and Clinical APACHI 2 parameters were completely normal in the first 2 days and started to change on the third day. He was admitted to the ICU for 10 days and received assisted ventilation by CPAP for 4 days, then he was discharged at the end of the 10th day from the ICU. In group A, one patient had suffered from remote complication (psuedopancreatic cyst) that resolved spontaneously, while three patients had suffered from complications in group B (the case of severe pancreatitis and another case of pancreatic abscess that was managed by pigtail and psuedopancreatic cyst that was managed by cystogastrostomy 6 months later); thus, the complications of group B were three times that of A with a P value of 0.001–0.05 which is statistically significant [Table 4].
|Table 2: Size of stones extracted in group A by endoscopic retrograde cholangiopancreatography|
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|Figure 1: Distribution of subcategories of group B patients (those who continue conservatism and those who were subjected to endoscopic retrograde cholangiopancreatography either urgently or electively).|
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|Table 3: Comparison between negative cases in group A and cases that were converted to endoscopic retrograde cholangiopancreatography in group B|
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The hospital admission time for the conservative group was four times that of the early ERCP counterpart with a P value of less than 0.0001 [Figure 2].
|Figure 2: Comparison between the mean hospital admission days of groups A and B.|
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Total economic burden in group A was 80 000 while in group B 43 500 [Figure 3]; thus, the early intervention limp had more economic burden though it had less complications and less mean hospital admission time.
| Discussion|| |
Acute pancreatitis is classified clinically to mild (those with inflammation only without neither organ failure nor local complications) or moderately severe (transient organ failure or local complications) or severe (persistent organ failure for more than 2 days. The mortality of mild pancreatitis is very rare while that of severe ranges from 35 to 50%. Pancreatitis evolves from mild to severe acute pancreatitis in a period that may reach 7 days. Early dislodging of an impacted stone can at least prevent superadded infection of obstructed pancreas and should be done as early as possible as persistent stone impaction may evolve pancreatic edema to hemorrhage and necrosis, while it is believed to have no effect on mortality or morbidity by others in the absence of cholangitis.
As regards the negative cases of group A they would be decreased theoretically by -pre-ERCP MRCP or intraoperative cholangiogram; however, it can be explained by that: first, MRCP has its own false negative results especially in micro-stones and muddy stones and in stones smaller than 6 mm and that most stones that cause pancreatitis are small with a size of less than 5 mm. Second, intraoperative cholangiogram has also its fallacies ranging from 4 to 60% by some authors although recent data suggest that it has sensitivity reaching 90%, thus, there is a minimum of 10% of stones to be missed by intraoperative cholangiogram,. However, many authors still insist on pre-ERCP imaging as Dr Moustafa M. Mourad and colleagues. As regards the duration of observation which was minimally 2 days for group B2 who were managed by urgent ERCP on the third day; 2 days were the minimal to compare two consecutive measurements of serum bilirubin and in spite of the fact that those cases had all the complications that occurred in group B (the conservative limp of the study). This reflects that the evolution in pancreatitis may occur early and may be within the first 48 h. We should notice that with observation policy it was impossible to perform ERCP within the golden 48 h as usually the patient comes to the hospital after 12 h of his complain in addition to 48 h of observation; thus, we have lost the golden hours. This was proved by the case that progressed to severe pancreatitis on the fourth day after ERCP and it had no risk factors of post-ERCP pancreatitis that can attribute severe pancreatitis to ERCP. The morbidity in the conservative limp was triple than that of the early intervention group and the hospital stay in the conservative limp was quadruple than that in the early intervention group and this may be due to the low volume of the sample. This fact was concordant with the Adrash P. Saleh conclusion that early ERCP is beneficial in the presence of cholangitis or biliary obstruction and with the UK guidelines also that suffice cholodocholithiasis to perform ERCP. The restriction of performance of ERCP in acute pancreatitis to cholangitis was only refuted by the large multicenter Dutch study. The main difference between our study and similar studies is that early ERCP was done randomly without dependence on the scoring system of severe pancreatitis to select the patients subjected to early ERCP and this was due to that the most sensitive scoring system (interleukin-6) has a 93% sensitivity in predicting severe pancreatitis and thus there is a 7% chance of the cases that will progress to severe pancreatitis to be missed, which is from one quarter to half of the overall cases that will progress to severe pancreatitis generally.
| Conclusion|| |
Early ERCP by a well-trained endoscopist is effective in reducing the complications and hospital admission time though it has more cost in patients with acute biliary pancreatitis.
The limitations of the study: the small sample size is the limitation of the study was its Achilles heel.
ERCP is preferred to be done before 48 h of patient's complication of biliary pancreatitis without dependence on scoring systems for prediction of the severity of pancreatitis due to their potential fallacies (7% by the best one which depends on interleukin-6).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Japp J, Candera S. Statepearls website. Acute Pancereatitis 2018; 2
Pancreatitis NICE guidelines, 2019. Available from: http//www.nice.org
. [Accessed September 2018]
Çiftçi F, Anuk T. Acute biliary pancreatitis in cholecystectomised patients. Northern Clin Istanbul 2017; 4
Dixit A, Dawra RK, Dudeja V, Saluja AK. Role of trypsinogen activation in genesis of pancreatitis. Michigan city, USA; Pancreapedia. 2016; Version 1.0
Lerch M Aghdassi A. Gallstone-Related Pathogenesis of Acute Pancreatitis
. Michigan city, USA; Pancreapedia 2016; 1–5.
Hazem ZM. Acute biliary pancreatitis: diagnosis and treatment. Saudi J Gastroenterol 2009; 15
Acosta JM, Rubio OG, Rossi R, Chinellato AV, Pellegrini CA. Effect of duration of ampullary gallstone obstruction on severity of lesions of acute pancreatitis. J Am Coll Surg 1997; 184
Kylänpää L, Rakonczay Z, O'Reilly DA. The clinical course of acute pancreatitis and the inflammatory mediators that drive it. Int J Inflamm 2012; 2012
Arkaprovo R. Complications of acute pancreatitis. Health Med 2017; 5
Cotton B. Therapeutic ERCP 2005; 5
Szary NM, Al-Kawas FH. Complications of endoscopic retrograde cholangiopancreatography: how to avoid and manage them. Gastroenterol Hepatol 2013; 9
Neoptolemos JP, London NJ, James D. Controlled trail of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative management for acute pancreatitis due to gallstones. Lancet 1988; 3
Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, van Erpecum KJ, Gooszen HG. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trial. Pancreas 2008; 247
Androlini A, Repisi A. Role and timing of ERCP in acute biliary pancereatitis. World J Gastroentrol 2015; 21
Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG,et al
. Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62
Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004; 53
Fan ST, Lai E, Mok F, Lo CM, Zheng SS, Wong J. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. N
Engl J Med 1993; 328
Li P, Zhang Z, Li J, Jin L, Han W, Zhang J. Diagnostic value of magnetic resonance cholangiopancreatography for secondary common bile duct stones compared with laparoscopic trans-cystic common bile duct exploration. Med Sci Monitor 2014; 20
Guarese A, Baten S, Mainardi P, Facioli N. Diagnostic accuracy of MRCP in cholodocholithiasis. Radiol Med 2005; 109
Deihl AK, Holleman DR, Chapman JB, Swichinger WH, Kuten WE. Gall stone size and risk of pancereatitis. Arch Internet Med 1997; 157
Sppin M, Wolf D, Verma D, Lukens FJ. Prediction which patient with abnormal intraoperative cholangiogram will have confirmed stones at ERCP. Dig Dis Sci 2010; 55
Shah AP, Mourad MM, Bramhall SR. Acute pancreatitis: current perspectives on diagnosis and management. J Inflamm Res 2018; 11
Hope WW, Fanelli R, Walsh DS, Narula VK, Price R, Stefanidis D, Richardson WS. SAGES clinical spotlight review: intraoperative cholangiography. Surg Endosc 2017; 31
Silverstein W, Isikoff MB, Hill MC, Barkin J. Diagnostic imaging of acute pancreatitis: prospective study using CT and sonography. Am J Roentgenol 1981; 137
UK working party on acute pancereatitis, UK guide lines for management of acute pancereatitis, BMJ, GUT, 2004. Available at: http/dx.doi.org/10.1136/gut2004.057026
. [Last accessed on 2005 Apr 29].
Van DIjk SM, Hallensleben ND, van Santvoort HC, Fockens P, van Goor H, Bruno MJ,et al
. Acute pancreatitis: recent advances through randomised trials. Gut 2017; 66
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]