ERCP-induced perforation: review and revisit after half a century

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most commonly utilized procedures for both diagnostic and therapeutic indications. It was first developed in clinical practice in 1968 as a diagnostic tool.¹ Cannulation of the ampulla and sphincterotomy were introduced in the early 1970s with consequent evolution of ERCP into a therapeutic procedure.^1,2 Nowadays ERCP is almost exclusively indicated for the therapy of hepatobiliary disorders since other less invasive diagnostic modalities (for example: magnetic resonance cholangiopancreatography (MRCP)) which possess similar sensitivity, are widely available.

In spite of the valuable contribution of ERCP in patients’ management, it is not a complication-free intervention. The ERCP-related morbidity was estimated to be 6.9%; it also carries a mortality rate of 0.33%.³ The spectrum of complications includes pancreatitis being the most common, followed by cholangitis, bleeding and perforation. The incidence of severe complications is approximately four times higher in ERCP than in other endoscopic procedures.⁴

One of the most feared complications is ERCP-induced perforation (EIP). Although EIP is uncommon, it is potentially fatal. Moreover, the treatment of such complication is still controversial.

This study represents the first analysis of EIPs in Jordan. Along with this analysis, we aimed to conduct a comprehensive review of literature for ERCP-induced perforations since the introduction of this procedure as a therapeutic intervention.

Methods

Results

A total of 996 ERCP procedures were performed by three experienced endoscopists (board certified gastroenterologist, licensed to perform endoscopy after training in an accredited structured ERCP program). Thirteen patients (1.34%) were diagnosed with EIP. Additionally, 43 other patients who also underwent ERCP, but with no endoscopic induced perforation were randomly selected as a control group, all patients had the procedure for the first time (Table 1).

EIP group: There were nine women (69%) and four men (31%) with a mean age of 52.6 years. Approximately two-thirds (69%) of patients had hypertension, 18.9% had diabetes mellitus while none were diagnosed to have ischemic heart disease. Only two patients (15%) had a history of abdominal surgery, both of which were laparoscopic cholecystectomy. One patient had pancreatic adenocarcinoma and another patient was known to have cholangiocarcinoma.

ERCP indications

By far, the most common indication for ERCP was obstructive jaundice (61%), followed by choledocholithiasis (23%). Other indications included gallstone pancreatitis and bile leak after cholecystectomy (Table 2).

ERCP characteristics

Dilated common bile duct (CBD) was observed in 31% of cases and 15% had a filling defect. Precut papillotomy was performed for 85% of the EIP group, 23% had a stone extracted during ERCP. Failure of cannulation was experienced in half of patients (six patients, 46%).

Discussion

In this study, we investigated the incidence rate of duodenal perforation among patients undergoing ERCP and compared patients’ and procedure’s characteristics to a control group. Our results revealed that perforations occurred in a comparable rate (1.34%) to published series. Our study also disclosed that failure to cannulate the CBD was the main predictor of perforation during ERCP.

The reported incidence of ERCP related perforations varied between 0.11% and 2.4%.^6,7 In one large analysis of 21 prospective surveys of post-ERCP complications in adults (16,855 patients) between 1977-2006, 101 patients experienced perforation (0.60%). The mortality rate in that study was 9.9%.³ In another review of 18 (mainly retrospective) studies conducted between 2000-2014, the incidence rate of EIP was 0.39%, with an overall mortality of 7.8%.⁸ Surprisingly, published numbers did not seem to decline significantly over the last 20 years as ERCP became more popular and widely available.

Published data revealed that the incidence rate of ERCP perforations corresponds with volume of cases at each institution, as highes-volume centers (which perform more than 1000 ERCPs per year) reported lower incidence rates (Bill et al., 0.44%, Jin et al., 0.27%, Kim J et al., 0.61%, Howard et al., 0.6%, Dubecz et al., 0.09%),^9–13 compared to the lower volume ones (less than 500 ERCPs per year) (Turner et al., 2.4%, Stapler et al., 1%, Miller et al., 1.65%, Rabie et al., 1.67%, Koc et al., 0.94%).^5,6,14–16 The correlation between incidence of perforation and volume of ERCP cases needs further analysis to elaborate statistical significance. These observations, however, indicate that ERCP remains an invasive procedure which may carry significant morbidity and mortality, even in skilled hands or at high volume units.

“Difficult cannulation” is a term employed to describe failure to gain access into the bile duct by the conventional cannulation technique. Factors that may contribute to this difficulty include presence of periampullary diverticula, altered anatomy and bulky papilla. In many studies, this situation has been defined as a leading cause of perforation.¹⁷ The risk is highest as precut papillotomy (or sphincterotomy) is attempted by the endoscopist to overcome this challenge. In Vezakis et al.’s review, endoscopic sphincterotomy was responsible for 41% of perforations.⁸ Another study by Stapfer and colleagues found that cannulation of the ampulla was considered difficult by the endoscopist in 10 of 14 patients who had perforations (out of 1413 ERCPs).⁵ In their review of 21 prospective reports of ERCP complications, Andriulli et al., found that the overall complication rate was significantly higher whenever therapeutic interventions were utilized during ERCP.³ Complications were also significantly higher in studies with a precut sphincterotomy rate of over 10%. Fifty years after the advent of therapeutic ERCP, difficult cannulation is still a frequently encountered condition, which may – although rarely – predispose to perforation and subsequent morbidity and death.

There appears to be a consensus on electing surgery for the treatment of free duodenal wall perforations (type I), which commonly present with signs of peritonitis.^12,18–20 In our group of patients with perforation, surgery was required in 5/13(38%), 4/5 of the operated patients had type I (free wall) perforation. Surgical intervention is conducted in higher risk injuries that are more likely to progress into sepsis, which explains – in part – the higher morbidity observed in this subgroup. Because duodenal or duct wall defect identification during surgery might be very challenging, especially if diagnosis is delayed (>6 hours post ERCP),^21,22 surgery can be limited to perform proper drainage and debridement of unhealthy tissue, which can reduce the risk of systemic manifestations and sepsis. Diversion surgeries (Roux-en-Y bypass) have been reported in management of large duodenal perforations.⁵ However, in ERCP most perforations are small, unless caused by the scope itself.

Endoscopic repair of duodenal perforations, particularly small defects(<10mm) that are recognized during ERCP has been reported.^23,24 The latter development of endoscopic clipping (through-the-scope clips), suturing and closure devices (ligation band, fibrin glue, and endo-loops) as well as covering luminal stents has made endoscopy more efficient in treating injuries similar to perforations and bleeding.^25–31 With the growing body of evidence supporting the use of these techniques for the management of ERCP complications, endoscopist expertise, perforation type and diameter remain important predictors of the outcomes.

In other types of perforation, i.e. types II, III and IV, the injury is less likely to manifest as peritonitis, but rather as retroperitoneal (and to a less extent intraperitoneal) fluid or air accumulation. Conservative measures in such circumstances vary from simply restricting oral intake with parenteral nutrition, hydration and coverage with broad spectrum antibiotics to percutaneous drainage of collections under ultrasound or CT guidance.

It is critical to recognize if leakage has stopped after the endoscopy or is still ongoing, as the patient may have experienced transient fluid extravasation during the procedure due to duct or duodenal wall puncture. The presence of enlarging pockets of pus or fluid collections, especially in the retroperitoneal space, does not necessarily indicate an active leakage, which can usually be excluded utilizing CT scan with water soluble contrast (Gastrografin), or fluoroscopic imaging (meal). This may instead indicate inadequate drainage or persistent infection that mandates repositioning of the drain, upgrading the size of the drain or placing another drain. It may also be helpful to consider adding antifungals after submitting samples for cultures.

The following are literature-based guidelines which can be driven to conclude when and how to intervene in patient with suspected or proved ERCP-induced perforation:

This study had some limitations. Firstly, it was a retrospective study. Secondly, the sample size of patients with EIP was relatively small to evaluate risk factors with statistical significance. Thirdly, we assume that a small group of patients with type IV perforation may have not been detected, due to lack of abdominal or systemic manifestations.

In conclusion, fifty years after introduction of ERCP for therapy, it remains an invasive procedure with certain complications that carry significant morbidity and mortality, even in skilled hands or at high volume units. Selection of patients for ERCP must be strict, it has to be done for therapeutic indications. Difficult cannulation is still a condition that is frequently encountered, and considered the main risk factor for perforation. Early diagnosis and appropriate surgical or percutaneous drainage yield favorable outcomes.

Author contributions

AM: investigation, methodology and project administration, ZM: resources, software, TM: software, analysis, HM: software, supervision, AH: methodology, resources, KJ: investigation, MH: methodology, NF: investigation, SS: resources, DA: resources, supervision, JF: methodology. All authors had substantial contribution to conception and design, interpretation of data, drafting, and revising the article. They all approved the final manuscript and agreed to be accountable for all aspects of the work.