INTRODUCTION — Perforation is one of the most feared complications of endoscopic retrograde cholangiopancreatography (ERCP). This topic review will focus on the risk factors, diagnosis, and treatment of post-ERCP perforation. An overview of the complications of ERCP and detailed discussions of other individual complications are presented separately. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults" and "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis" and "Post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding" and "Uncommon complications of endoscopic retrograde cholangiopancreatography (ERCP)".)
CLASSIFICATION — Four types of perforation complicating endoscopic retrograde cholangiopancreatography (ERCP) have been recognized [1,2]. The Stapfer classification is most commonly used and is based on the mechanism, anatomical location, and severity of the injury that may predict the need for surgical intervention (figure 1) [2]:
●Type I: Free bowel wall perforation
●Type II: Retroperitoneal duodenal perforation secondary to periampullary injury
●Type III: Perforation of the pancreatic or bile duct
●Type IV: Retroperitoneal air alone
Of these, retroperitoneal duodenal perforations are the most common. In a case series of 44 post-ERCP perforations, 30 (68 percent) were retroperitoneal duodenal perforations, which usually occur as a result of a sphincterotomy that extends beyond the intramural portion of bile duct [3]. Perforation of the pancreatic or bile duct usually occurs following dilation of strictures, forceful cannulation, guidewire insertion, stent migration, or difficult stone extraction [4-12]. Liver and pancreatic parenchymal perforation by the guidewire during ERCP is an under-appreciated complication, and subcapsular liver hematoma and subcapsular biloma can occur in this context [13,14]. (See "Uncommon complications of endoscopic retrograde cholangiopancreatography (ERCP)".)
Free abdominal perforation of the duodenum or jejunum is rare, usually occurring in patients with a stricture or anomalous anatomy, such as Billroth II gastrectomy [15-18]. (See "Endoscopic retrograde cholangiopancreatography (ERCP) after Billroth II reconstruction" and "ERCP in patients with Roux-en-Y anatomy".)
In a single-center series, 79 post-ERCP perforations were diagnosed: seven perforations were type I, 54 were type II, nine were type III, six were type IV, and three were hypopharyngeal or esophageal [18]. While most patients with Type II perforations were medically managed, four patients from this group (7 percent) required surgical intervention.
Gastric and esophageal perforation [4,19,20] and pneumomediastinum without evidence of perforation [21] have also been described after ERCP and sphincterotomy. Intestinal perforation related to biliary stents is an uncommon complication. (See "Uncommon complications of endoscopic retrograde cholangiopancreatography (ERCP)".)
INCIDENCE — Retroduodenal perforation was reported in 0.5 to 2.1 percent of sphincterotomies in a number of older large series [22]. The incidence of perforation has appeared to decrease to less than 0.5 percent, probably because of improvement in experience and skill of endoscopists [23]. However, severe and fatal cases continue to occur [24,25]. In a summary of 21 prospective studies involving 16,855 patients undergoing diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) between 1987 and 2003, post-ERCP perforations totaled 101 (0.60 percent), with 10 deaths (0.06 percent) [26].
Numerous primarily retrospective studies published have described perforation rates following ERCP (table 1) [1-4,11,12,27-53]. Overall, the risk of perforation following ERCP is approximately 0.4 percent, with a mortality rate of approximately 7 to 8 percent. Type I perforations account for 25 percent of perforations, type II for 46 percent, type III for 22 percent, and type IV for 3 percent [50]. (See 'Classification' above.)
RISK FACTORS — A number of patient- and procedure-related risk factors for perforation have been identified in individual reports and in large series. A difficulty with interpreting the risk factors identified in these reports is that many of the studies combined free bowel wall perforation at a site remote from the papilla (endoscope-related) and periampullary retroperitoneal perforation (sphincterotomy-related). The mechanisms leading to the different types of perforations are substantially different. Furthermore, the absolute number of patients studied is small, reflecting the infrequent occurrence of these complications.
All perforations — The following risk factors for free abdominal or retroperitoneal perforation were identified in a large retrospective case-control study that included 33 endoscopic retrograde cholangiopancreatography (ERCP)-related perforations out of 9314 ERCP procedures [4]:
●Patient-related risk factors included sphincter of Oddi dysfunction and a dilated common bile duct. Sphincter of Oddi dysfunction has also been recognized as a risk factor [54,55]; however, it is usually in conjunction with a small, rather than a dilated, common bile duct [54,55]. A possible explanation for this difference is that the dilated common bile duct in one series was due to a distal common bile duct stricture, and the increased risk of perforation in this group was related to the manipulations carried out to obtain deep cannulation.
●Procedure-related risk factors included performance of a sphincterotomy, longer duration of the procedure, and biliary stricture dilation.
A grading system for assessing the complexity of ERCP has been proposed to predict rates of cannulation success and perforation, while further studies are anticipated [56].
Bowel wall perforation — The risk of bowel wall perforation is increased in patients who have stenosis in the upper gastrointestinal tract or bile ducts, and in patients with abnormal gastrointestinal anatomy, such as gastrectomy, pancreaticoduodenectomy, situs inversus, or periampullary diverticula [15,16,18,28,57,58]. Particular caution is required with the use of a side-viewing duodenoscope (the endoscope typically used for ERCP) in patients with a Billroth II gastrectomy [57,59]. (See "Endoscopic retrograde cholangiopancreatography (ERCP) after Billroth II reconstruction".)
Retroperitoneal perforation — The risk of retroperitoneal perforation is increased with precut sphincterotomy and larger sphincterotomies, particularly those that are created outside of the usually recommended landmarks (11 to 1 o'clock) [60-63]. In one report, 7 of 13 sphincterotomy perforations were related to precutting [4]. (See "Precut (access) papillotomy".)
ERCP with ampullectomy is a risk factor for retroperitoneal perforation. In a study of 104 patients who underwent ampullectomy, the perforation rate was 8 percent [64]. In a retrospective Italian study between 1999 and 2011, an ampullectomy had been performed in 7 out of 30 cases (23 percent) of duodeno-pancreato-biliary perforations reported after ERCP [65]. (See "Ampullary adenomas: Management".)
Other risk factors identified in individual reports include a small caliber bile duct [66], the presence of a peripapillary diverticulum [62,67], and intramural injection of contrast [60].
Biliopancreatic ductal perforation — Biliary stricture dilation increases the risk of biliopancreatic perforation [4].
CLINICAL MANIFESTATIONS AND DIAGNOSIS — Free abdominal perforation (type I perforation) is almost always recognized immediately based upon clinical symptoms, physical signs, and fluoroscopic findings. By contrast, retroduodenal perforation (type II) is usually determined by radiologic evidence of air (image 1) or contrast in the retroperitoneal space outside the confines of the bile duct and duodenum during ERCP or computed tomographic (CT) evaluation for post-ERCP pain. However, type II perforations may be evident endoscopically (picture 1).
A retrospective series of ERCPs performed between 2010 and 2014 that included 61 type I or II duodenal perforations found that the diagnosis was made during the procedure in six patients (10 percent) and after the procedure in 54 patients (90 percent). The mean time to diagnosis was 24 (+/-13) hours [18]. However, other studies suggest that the rate of detection during ERCP may be higher [50,51]. For example, in a review of 18 studies with a total of 437 perforations, the diagnosis of perforation was made during ERCP in 321 cases (73 percent) [50].
Patients with undetected leaks can present hours after the procedure with pain, fever, and leukocytosis. Pneumomediastinum and subcutaneous emphysema can occur [21,68-72]. Pneumothorax [73] and gas in the portal system [74] have also been rarely described. Case reports have documented patients who developed pneumoretroperitoneum, pneumoperitoneum, pneumomediastinum, pneumothorax, and subcutaneous emphysema following ERCP [75-78]. Indeed, an anatomic continuum exists between the retroperitoneum, pneumoperitoneum, mediastinum, pneumothorax, and subcutaneous tissues. As a result, ectopic air in one of these compartments can extend to distant communicating spaces [79].
An abdominal CT scan should be obtained in patients who are suspected of having a perforation, even if they do not have evidence of retroperitoneal air on plain films, since CT scan is the most sensitive means for detecting perforation [80,81]. The clinical or radiographic amount of air does not always indicate the size of the perforation or correlate with the severity of the complication, but rather reflects the degree of manipulation after the perforation occurred [80,82].
Retroperitoneal air in asymptomatic patients — As discussed above, perforation is typically associated with the presence of retroperitoneal air, which can be detected by plain radiographs or CT. However, retroperitoneal air may also develop following sphincterotomy in patients who are clinically asymptomatic [81,83]. Such patients may not require intervention. This was illustrated in a series of 21 patients studied prospectively who underwent an abdominal CT scan following sphincterotomy. Retroperitoneal air was observed in six (29 percent) patients, all of whom were asymptomatic and had an uneventful postprocedural course [83]. No clinical or procedure-related characteristics predicted the presence of air.
The origin of retroperitoneal air in such patients is presumably related to dissection through an injured or macroscopically intact bowel, which has also been described after colonoscopy [84,85], although sealed microperforations are also possible. These findings suggest that the presence of retroperitoneal air in the absence of symptoms should warrant careful observation but may not require intervention.
Retroperitoneal perforation associated with pancreatitis — The finding of retroperitoneal air may be challenging in patients who are symptomatic following sphincterotomy in whom a distinction needs to be made between perforation, clinically insignificant retroperitoneal air, and pancreatitis, particularly since pancreatitis and perforation can have a similar clinical presentation or occur simultaneously [74,80,86]. This was illustrated in a study that included 36 patients who developed prolonged abdominal pain following sphincterotomy and underwent a diagnostic CT scan. Complications included acute pancreatitis in 23 patients (64 percent), duodenal perforation in 11 (31 percent), and both pancreatitis and duodenal perforation in six patients (17 percent) [80]. In a series that included 61 type I or II duodenal perforations, concurrent post-ERCP pancreatitis was diagnosed in 26 patients (43 percent) and was associated with increased mean length of stay [18]. In another series, two of three perforations in patients with Billroth II anatomy were associated with acute pancreatitis [87]. The diagnosis of retroperitoneal duodenal perforation associated with pancreatitis should be based upon the detection of retroperitoneal air or contrast in a symptomatic patient meeting criteria for post-ERCP pancreatitis. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".) A retroperitoneal abscess should be suspected in patients with post-ERCP pancreatitis who develop back pain and persistent fever [88].
GRADING — Post-endoscopic retrograde cholangiopancreatography (ERCP) retroperitoneal perforation can be graded as mild, moderate or severe, based upon a consensus definition [22]:
●Mild – Possible, or only very slight leak of fluid or contrast, treatable by fluids and suction for three days or less
●Moderate – Any definite perforation treated medically for 4 to 10 days
●Severe – Medical treatment for more than 10 days or intervention (percutaneous or surgical)
MANAGEMENT
General principles — All patients should be kept fasting while receiving hydration, nasogastric or nasoduodenal suction, and intravenous antibiotics. If immediately diagnosed, type I perforations (free bowel wall perforations) can sometimes be successfully treated endoscopically [89]. However, patients with esophageal and free abdominal gastric, jejunal, or duodenal perforation usually require surgery [4,90].
By contrast, a conservative approach to retroperitoneal perforation following endoscopic sphincterotomy has been adopted over the years [2,11,12,28,31]. However, early surgical consultation and careful observation is mandatory since the outcome may be poor in patients who do not receive prompt and appropriate treatment [1,91-94]. For example, in a retrospective study of 380 patients with ERCP-related perforation, 330 patients (87 percent) were managed nonoperatively, while 50 patients (13 percent) required surgical intervention [92]. For 20 of 50 surgical patients, surgery was performed 24 hours after ERCP, and delayed surgery was associated with higher rates of mortality and post-operative duodenal leak compared with early surgery (50 versus 20 percent, and 75 versus 23 percent, respectively).
Medical management — Patients with a post-ERCP perforation should be kept fasting while receiving intravenous hydration, nasogastric or nasoduodenal suction, and intravenous antibiotics. Patients who are expected to require bowel rest for one week should be placed on total parenteral nutrition.
Surgery — Overall, surgery was required in 20 to 50 percent of patients with a perforation in most reports (table 1) [3,4,11,12,18,22,32-36,50,52,60,65,90,95-97]. Surgery was most often needed in patients with free bowel wall perforations. Surgery should be recommended for patients with a major contrast leak, persistent biliary obstruction, or cholangitis, and for those whose symptoms do not improve after a brief period of nonoperative management [94]. Surgical options include choledochotomy with stone extraction and T-tube drainage, repair of the perforation, drainage of an abscess or phlegmon, choledochojejunostomy, or pancreatoduodenectomy [65,94,98-100]. (See "Repair of common bile duct injuries".) .
The location of the perforation in cases of endoscopic retrograde cholangiopancreatography (ERCP)-associated injury may not be identified at laparotomy [11].
Patients who require surgery have a high mortality rate. In a review that included 11 studies, surgery was required in 29 out of 137 patients with Type II perforations (21 percent), with an overall mortality rate of 9.4 percent. However, the mortality rate in patients who required surgery was 38 percent (11 of 29) [50].
Endoscopic therapy — Endoscopic therapeutic options to manage ERCP-related perforations include:
•Through-the-scope clips – The effective and safe placement of metallic endoclips in the treatment of duodenal perforation secondary to sphincterotomy has been reported [37,101,102]. Effective endoscopic closure of duodenal perforations caused by the tip of the endoscope during ERCP using endoclips has also been reported [97,103,104]. However, endoscopic therapy of a duodenal perforation is much more difficult than that of a colonic or gastric perforation.
•Endoscopic purse-string suture – The endoscopic purse-string suture uses endoscopically placed loops and clips to repair of perforations of the gastrointestinal tract. It has been reported that this technique was successfully employed with a double-lumen endoscope for closing a large perforation on the lateral duodenal wall [105].
•Over-the-scope clip – In case reports, a post-ERCP jejunal perforation in a patient with Billroth II anatomy [106] and a large post-ERCP retroperitoneal duodenal perforation [107] were effectively closed with an over-the-scope clip device. However, this endoscopic treatment in general should only be considered in patients who are inoperable, are not septic, and have only a minimal peritoneal fluid collection [108].
•Fibrin glue – In a case report, the injection of fibrin glue proved effective in sealing a perforation located in the posterior wall of the duodenal bulb [109]. Fibrin sealant injection successfully occluded a retroperitoneal perivaterian perforation after sphincterotomy in a case report where previously a computed tomography-guided abscess drainage had been performed and the biliary orifice had been protected by a stent [110]. Additional study of the use of fibrin glue for perforations is needed.
•Covered stents – Effective temporary placement of fully covered self-expandable metal stents for the treatment of perforation following endoscopic sphincterotomy has been reported in selected cases. The clinical outcomes were encouraging, but further studies are required [18,111-116].
•Band ligation – Successful repair of lateral duodenal post-ERCP perforations has been reported using a band [117].
•Endoscopic vacuum therapy – A case of successful drainage of an iatrogenic retroperitoneal duodenal perforation following ERCP with papillotomy was reported from Hamburg, Germany, using a vacuum technique [118]. The distal end of a drainage tube, wrapped in a very thin, open-pore, double-layered drainage film and secured using a suture was inserted nasally and then advanced into the duodenal lumen under endoscopic view. A vacuum was applied, resulting in collapse of the stomach and duodenum around the tube. Gastric, biliary, and pancreatic secretions were drained via the open-pore tube. Once the perforation healed (after six days in the report) the tube was removed.
•Whether or not the therapeutic goal of ERCP was achieved, a nasobiliary tube can be placed in an attempt to aspirate bile and minimize retroperitoneal contamination if a retroperitoneal perforation is recognized during the procedure, but not at the price of marked prolongation of the procedure.
Percutaneous drainage methods — Percutaneous transhepatic drainage (see "Percutaneous transhepatic cholangiography") is an alternative to surgery for patients who develop localized retroperitoneal fluid collections [96,100].
PROGNOSIS — The prognosis of patients with a perforation depends upon the rapidity with which it is recognized, the clinical setting, and patient comorbidities. The overall mortality was 16 percent in an older report that summarized the outcomes of 153 perforations following endoscopic sphincterotomy [22]. Overall mortality was 6 percent (seven out of 115 patients) in five large series between 1987 and 2004 [4,38,60,95,119], and a mortality rate of 8 percent (20 out of 251 patients) was demonstrated in a review that considered major studies from the year 2000 onwards [120]. An overall mortality of 13 percent (four deaths out of 30 cases) and a postoperative mortality of 27 percent (four deaths out of 15 cases) were reported in a retrospective study from Italy between 1999 and 2011 [65]. The overall need for surgery after perforation was approximately 35 percent and the mortality was approximately 7 percent, according to results from observational studies (table 1) [1-4,11,12,27-48,51,52]. The lower mortality seen in many of the more recent studies may reflect the benefits related to a conservative team approach for the management of small retroperitoneal perforations.
PREVENTION — The risk of perforation can be minimized when endoscopic retrograde cholangiopancreatography (ERCP) is performed by well-trained endoscopists and assistants abiding by the following technique-related principles [54]:
●Proper orientation of the sphincterotome between 11 and 1 o'clock.
●Step-by-step incision.
●Avoiding a "zipper" cut.
●Sphincterotomy length tailored to the size of papilla, bile duct, and eventual stone. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy".)
●Judicious use of precut papillotomy. (See "Precut (access) papillotomy".)
●Appropriate technique in cases of anatomical variants such as peripapillary diverticula and Billroth II gastrectomy. (See "Endoscopic retrograde cholangiopancreatography (ERCP) after Billroth II reconstruction" and "ERCP in patients with Roux-en-Y anatomy".)
●Use of balloon dilatation in conjunction with sphincterotomy in patients with large bile duct stones, rather than relying on sphincterotomy alone [121-123], though severe perforations have been noted with this technique as well [122]. In a retrospective study from China comparing small sphincterotomy combined with endoscopic papillary large balloon dilation (group A) versus sphincterotomy alone (group B) for removal of large common bile duct stones involving a total of 153 patients, there were no perforations in either group and the rate of bleeding was significantly lower in group A (1.6 versus 5.6 percent) [124]. (See "Endoscopic balloon dilatation for removal of bile duct stones".)
●Carbon dioxide (CO2) insufflation is an alternative to air insufflation. Carbon dioxide is absorbed from the gastrointestinal tract approximately 160 times faster than nitrogen and its use can reduce abdominal pain and discomfort after endoscopic procedures. The role of CO2 insufflation during ERCP is not yet established but it can theoretically minimize the degree of retroperitoneal gas in the event of ERCP-related perforation [125]. Larger trials are needed to further assess the role of CO2 during ERCP.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endoscopic retrograde cholangiopancreatography (ERCP)" and "Society guideline links: Gastrointestinal perforation".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Four types of perforation complicating endoscopic retrograde cholangiopancreatography (ERCP) have been recognized. (See 'Classification' above.):
•Type I: Free bowel wall perforation
•Type II: Retroperitoneal duodenal perforation secondary to periampullary injury
•Type III: Perforation of the pancreatic or bile duct
•Type IV: Retroperitoneal air alone
●Retroduodenal perforation was reported in 0.5 to 2.1 percent of sphincterotomies in a number of older large series. Over time, the incidence of perforation has appeared to decrease to less than 0.5 percent, probably because of improvement in experience and skill of the endoscopists. (See 'Incidence' above.)
●Free abdominal perforation is almost always recognized immediately based upon clinical symptoms, physical signs, and fluoroscopic findings. By contrast, retroduodenal perforation is usually determined by the radiologic evidence of air or contrast in the retroperitoneal space outside the confines of the bile duct and duodenum during computed tomographic (CT) evaluation for post-ERCP pain. Perforation is rarely evident endoscopically. (See 'Clinical manifestations and diagnosis' above.)
●Retroperitoneal air may also develop following sphincterotomy in patients who are clinically asymptomatic. Such patients may not require intervention. (See 'Retroperitoneal air in asymptomatic patients' above.)
●An abdominal CT scan should be obtained in patients who are suspected of having a perforation, even if they do not have evidence of retroperitoneal air on plain films, since CT scan is the most sensitive means for detecting perforation. (See 'Clinical manifestations and diagnosis' above.)
●Patients with esophageal and free abdominal gastric, jejunal, or duodenal perforation usually require surgery. By contrast, a conservative approach to small retroperitoneal perforation may be appropriate. However, early surgical consultation and careful observation is mandatory since the outcome may be poor in patients who do not receive prompt and appropriate treatment. (See 'Management' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Francesco Ferrara, MD, for his contributions as author to prior versions of this topic review.
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104 : Iatrogenic duodenal perforation treated with endoscopic placement of metallic clips: a case report.
105 : ERCP-induced duodenal perforation successfully treated with endoscopic purse-string suture: a case report.
106 : Endoscopic "retroperitoneal fatpexy" of a large ERCP-related jejunal perforation by using a new over-the-scope clip device in Billroth II anatomy (with video).
107 : Colic and gastric over-the-scope clip (Ovesco) for the treatment of a large duodenal perforation during endoscopic retrograde cholangiopancreatography.
108 : Endoscopic Retrograde Cholangiopancreatography-Related Large Jejunal Perforation: Operate or Apply Over-the-Scope Clip Device?
109 : Successful endoscopic closure of a lateral duodenal perforation at ERCP with fibrin glue.
110 : Endoscopic fibrin sealant closure of duodenal perforation after endoscopic retrograde cholangiopancreatography.
111 : Closure of a persistent sphincterotomy-related duodenal perforation by placement of a covered self-expandable metallic biliary stent.
112 : Endoscopic sphincterotomy-related perforation in the common bile duct successfully treated by placement of a covered metal stent.
113 : Short-term stenting using fully covered self-expandable metal stents for treatment of refractory biliary leaks, postsphincterotomy bleeding, and perforations.
114 : A case of ampullary perforation treated with a temporally covered metal stent.
115 : Value of temporary stents for the management of perivaterian perforation during endoscopic retrograde cholangiopancreatography.
116 : Can a Fully Covered Self-Expandable Metallic Stent be Used Temporarily for the Management of Duodenal Retroperitoneal Perforation During ERCP as a Part of Conservative Therapy?
117 : Successful closure of lateral duodenal perforation by endoscopic band ligation after endoscopic clipping failure.
118 : Successful endoscopic vacuum therapy with new open-pore film drainage in a case of iatrogenic duodenal perforation during ERCP.
119 : Complications of ERCP: a prospective study.
120 : Management of duodenal perforation post-endoscopic retrograde cholangiopancreatography. When and whom to operate and what factors determine the outcome? A review article.
121 : Endoscopic sphincterotomy plus large-balloon dilation versus endoscopic sphincterotomy for removal of bile-duct stones.
122 : Large-diameter biliary orifice balloon dilation to aid in endoscopic bile duct stone removal: a multicenter series.
123 : Large size balloon dilation of the ampulla after biliary sphincterotomy can facilitate endoscopic extraction of difficult bile duct stones.
124 : Small sphincterotomy combined with endoscopic papillary large balloon dilation vs sphincterotomy alone for removal of common bile duct stones.
125 : Carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography: A meta-analysis and systematic review.