Post ERCP Perforation Joint Hospital Surgical Grand Round October 21, 2017 Winston Wong Kwan Kiu YCH

ERCP Introduced by McCune in 1968 Overall complications: up to 10% Mortality: 0.1 to 1% Reserved mainly for therapeutic purposes nowadays ERCP was introduced by Dr. McCune in 1968. It’s a valuable tool allowing both diagnostic and therapeutic purposes in hepatobiliary diseases. However as an invasive procedure it has its share of complications, with complication rate up to 10% and overall quoted mortality from 0.1 to 1%. MRI has surpassed ERCP as the main modality for diagnosis of biliary diseases, so ERCP nowadays serve mainly for therapeutic purposes.

Complications Overall mortality: 0.34% Major complications: Pancreatitis: 3.5% Bleeding: 1.3% Perforation Incidence: 0.3 to 2% Mortality rate: 7 to 25% The overall quoted mortality rate is around 0.3%. Major complications can include pancreatitis, bleeding, and perforation. For my presentation I will focus mainly on perforation by ERCP. Andriulli et al, 2007. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007;102(8):1781

Risk factors for perforation Patient factors Old age Suspected Sphincter of Oddi dysfunction Dilated bile duct Papillary stenosis Abnormal anatomy e.g. Billroth II reconstruction Procedural factors Precut sphincterotomy Long procedure duration Biliary stricture dilatation Operator factors Experience In particular, Billroth II reconstruction is associated with higher duodenal perforation rate Enns et al, 2002. ERCP-related perforations: risk factors and management. Endoscopy 34:293-98

During ERCP… Obvious perforation on endoscopic view Contrast extravasation or free gas on fluoroscopy

After ERCP… Sign & symptoms Blood tests Usually nonspecific Severe epigastric pain Vomiting Fever Epigastric tenderness progressing to board- like rigidity Blood tests Also non-specific Leukocytosis Amylase Raised amylase points to post-ERCP pancreatitis but may be concurrent with perforation!

1 2 3 Management Resuscitation Establish diagnosis Select candidates who require surgical management 3 Management

Resuscitation NPO Parenteral antibiotics IVF / Parenteral nutrition Continuous close monitoring +/- Nasogastric drainage

Diagnosis CT Higher sensitivity than XR for detecting extraluminal liquids Detects small amount of free gas Evaluate efficacy of endoscopic perforation closure with oral contrast #2, diagnosis. While intra-peritoneal gas can be seen in XR, CT is the main choice for imaging.

Surgery or not? One of the most used classification for ERCP related perforation was established by Stapfer in 2000. Stapfer classified perforations to 4 types in decreasing order of severity. Type 1: usually large tears, remote from papilla, caused by the endoscope or stent, have considerable spillage. Type 2: peri-ampullary perforations, generally retroperitoneal, occur during sphincterotomies. Type 3: bile duct injuries, caused by instrumentation / stenting near an obstruction, usually small Type 4: tiny retroperitoneal microperforations, by compressed air. Others such as Enns and Howard have similar classifications. The authors usually agree on surgery for duodenal perforation (Stapfer Type 1), but some controversy remains for optimal management of other types of perforation. In the next few slides I will show several suggested algorithms. ----------------------------------- Type 1: (20%) usually large tears, remote from papilla, caused by the endoscope or stent, have considerable spillage requiring aggressive surgical intervention. Type 2: peri-ampullary perforations, generally retroperitoneal, occur during sphincterotomies, usually for conservative or minimally invasive techniques. Type 3: bile duct injuries, caused by instrumentation / stenting near an obstruction, usually small, amenable for conservative management. (Majority are types 2 & 3) Type 4: tiny retroperitoneal microperforations, by compressed air, for conservative management. Agree on surgery for duodenal wall perforation (Stapfer type 1)

Kumbhari et al 2016. Gastrointestinal Endoscopy 83(5): 934-43 John Hopkins Hospital, USA This is an algorithm proposed by GI physicians and surgeons from John Hopkins Hospital, published in 2016. Stapfer III and IV are not mentioned as most studies show excellent results from nonsurgical management alone. For those with suspected duodenal perforation, they undergo a plain CT with oral contrast to confirm any duodenal perforation Primary repair is done for Type 1 injuries with early diagnosis, i.e. <12 hrs Primary repair +/- duodenal exclusion is done for Type 1 injuries with delayed diagnosis, or failure of medical therapy for other types of injuries ----------------------------------- Intra-procedural diagnosis of perforation: 10%

(Duodenum lateral wall or jejunum injuries) (Periampullary & bile duct injuries) This algorithm was proposed by a Korean group from the Seoul National University in 2012. They further simplied the injuries into two groups, either duodenal injuries (i.e. Type 1) and “all other injuries” (Type 2), as their experience shows non-type 1 injuries usually have successful outcomes with conservative management. Of interest is that they added option of endoscopic clipping; if possible it should be done for type 1 injuries recognized early, otherwise they should proceed with operation Otherwise, their suggestion is more or less similar for their non-duodenal injuries, that is, conservative measures and continued evaluation and go for surgery if deterioration ---------------------------------------------- Rate of perforation: 0.63% Therapeutic (vs diagnostic): 84.9% Type I injuries 39.6% Type II injuries 60.4% Immediately detected perforation: 73.6% Morbidity: 34% Mortality: 5.7% Indication for surgery: (1) remaining problem unsolved by endoscopic procedure that requires immediate correction (e.g. retained hardware / stone), (2) duodenum lateral wall or jejunum injury without possibility of minimal leakage through adhesions or interventions, (3) initial / subsequent symptoms / signs of severe sepsis / peritonitis Kwon et al 2012. Journal of Korean Surgical Society 83:218-226 Seoul National University, Korea

The European Society of Gastrointestinal Endoscopy has came up with a position statement in 2014 regarding iatrogenic endoscopic perforations, with a section mentioning ERCP related perforations. Paspatis et al, 2014. Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 46(8):693-711

Stapfer Type I perforations 1) For Stapfer type 1 perforations, endoscopic closure should be tried if immediately discovered. 2) If there is delayed recognition, CT should be done. The main point being surgery is indicated if there is intra-abdominal fluid or extravasation. Free air alone may warrant trial of non-surgical management. Paspatis et al, 2014. Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 46(8):693-711

Non-Stapfer Type I perforations For non-Stapher type 1 perforations, main point is if there is peritonitis or sign of toxicity while on supportive measure, then patient should go for surgery If perforation discovered during ERCP, aim for supportive measure +/- biliary drainage If perforation discovered after ERCP, CT should be done to see if any significant collection requires drainage, whether percutaneous or endoscopic Paspatis et al, 2014. Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 46(8):693-711

Surgical management Indication Free intra-abdominal air Peritonitis Worsening sepsis Retained apparatus (e.g. trapped basket)

Surgical management Choices Primary repair & drainage +/- patch ECBD + T-tube Tailored to the type of injury, indication of ERCP, timing, and patient’s general condition Simplest damage control therapy Adequate drainage & lavage of possible sites of contamination Pyloric exclusion + GJ Since mortality rate of duodenal perforation is relatively high at 16-18%, early surgical closure is standard treatment. Consider simplest damage control therapy possible, since patients are usually fragile and in a catabolic state from peritonitis or malignancy. Repair may be difficult as the tissue may no longer be soft and extensively involved by inflammation. Diverticulization: truncal vagotomy, antrectomy with gastrojejunostomy, duodenal closure, tube duodenostomy, closure of duodenal perforation, drainage of CBD, external drainage Duodenal diverticulization

Endoscopic management Endoclips alone Endoclips + Fibrin glue Endoclips + Endoloop (for larger perforations) EBL +/- Endoclips Novel devices e.g. over the scope clips (Ovesco) Endoscopic management may be feasible as 1) perforations are recognized early during procedure, 2) lower chance of bacterial contamination in a fasting state. Prerequisites for endoscopic closure are 1) operator skill and familiarity with device, 2) immediate availability, 3) cost Efficacy is poorly established as there are limited cases in literature with perforation and endoscopic closure done.

EBL + Endoclip Park 2016. Clin Endosc. Jul;49(4):376-82 Endoscopic band ligation closure followed by endoclip to secure band Park 2016. Clin Endosc. Jul;49(4):376-82

EBL + Endoclip Kim et al 2017. Clin Endosc. Mar;50(2):202-205 Gastroscopic findings of duodenal wall perforation during endoscopic retrograde cholangiopancreatography and closure with double band ligation and endoclipping. (A) Duodenal wall perforation caused by insertion of the lateral scope into the second portion of the duodenum. The peritoneal contents were visible through the 2.0-cm perforation. (B) Partial closure of the duodenal perforation via the first band ligation. (C) Closure of the duodenal perforation including the duodenal wall and peritoneal fat with double band ligation. (D) Complete closure of the duodenal perforation with endoclipping after double band ligation. (E) Diagrammatic representation of the band ligation and endoclipping procedures for the repair of large duodenal perforations.

Endoclip + fibrin glue Lee et al 2013. Clin Endosc. 46(5):522-28 Endoclip followed by fibrin glue. Glue causes multiple clips to adhere to each other, and provide a cushion effect below the base of the perforation. Lee et al 2013. Clin Endosc. 46(5):522-28

Endoclip + Endoloops Lee et al 2013. Clin Endosc. 46:522-28 Endoloop can be used with endoclips to close a defect. On the left diagram, after placement of the endoloop around the perforated area, multiple clips are attached to the endoloop, then the endoloop is tightened thus closing the perforation. On the right is an alternate method for closing. The endoloop is used to approximate 2 endoclips over each side of the defect. This is repeated to close the entire defect. Lee et al 2013. Clin Endosc. 46:522-28

OTSC (Ovesco) Lee et al 2013. Clin Endosc. 46:522-28 Over-the-scope clipping system, shown here is the Ovesco system. Lee et al 2013. Clin Endosc. 46:522-28

Any consensus? No high quality evidence No definite guidelines No RCTs due to ethical problems and rarity of perforations In the end, there is no high quality evidence so far on this topic. No RCTs are done due to the ethical implications and perforations are rare events. Therefore there are still no definite guidelines on managing ERCP perforations

Take home messages Prevention better than treatment. ERCP is a highly specialized procedure that should be done by experienced, skilled endoscopist to minimize complications. Stapfer Type 1 (duodenal perforations) are best managed by surgery. Endoscopic repair is a promising option in expert hands if recognized early. Non-duodenal perforations are managed supportively. Close monitoring is required to avoid delay in surgical treatment. ERCP is a highly specialized procedure that should only be done by experienced, skilled endoscopists.

Thank you! Joint Hospital Surgical Grand Round October 21, 2017 Winston Wong Kwan Kiu YCH Senderey A et al, 2017. Management of endoscopic retrograde cholangiopancreatography-related perforations: Experience of a tertiary center. Surgery 161(4): 920-929. Dubecz et al, 2012. Management of ERCP-related small bowel perforations: the pivotal role of physical investigation. Can J Zsur 55(2): 99-104. Kwon et al, 2012. Proposal of an endoscopic retrograde cholangiopancreatography-related perforation management guideline based on perforation type. Lee et al, 2013. Endoscopic Treatments of Endoscopic Retrograde Cholangiopancreatography-Related Duodenal Perforations. Clin Endosc. 46: 522-528. Stapfer et al, 2000. Management of Duodenal Perforation After Endoscopic Retrograde Cholangiopancreatography and Sphincterotomy. Annals of Surgery 232(2): 191-98. Kumbhari et al, 2016. Algorithm for the management of ERCP-related perforations. Gastrointestinal Endoscopy 83(5): 934-43. Park, 2016. Recent Advanced Endoscopic Management of Endoscopic Retrograde Cholangiopancreatography Related Duodenal Perforations. Clinical Endoscopy 49(4): 376-382. Kim et al, 2017. Repair of an Endoscopic Retrograde Cholangiopancreatography-Related Large Duodenal Perforation Using Double Endoscopic Band Ligation and Endoclipping. Clinical Endoscopy 50(2): 202-205. Lee et al, 2013. Endoscopic Treatments of Endoscopic Retrograde Cholangiopancreatography-Related Duodenal Perforations. Clinical Endoscopy 46(5): 522-28.

Non-surgical management Insert biliary stent Watch out for Intra-abdominal fluid collection Need drainage (percutaneous / surgical) Sepsis High morbidity and mortality with longer hospital stay in failed case or those delayed >24 hrs before surgery Consider water soluble contrast study prior to resuming diet

Dubecz et al, 2012. Can J Surg, 55(2): 99-104 Nuremberg Hospital, Germany This is a retrospective study by a German group in 2012 from one of the largest hospitals in Germany. The study involved ~12000 patients, with ERCP-related perforation rate of 0.08% (i.e. 11 patients). 2 patients had a Bilroth II gastrectomy. 4 patients received surgery and survived. 7 patients received conservative Mx; 5 were successful and 2 patients died (both patients were offered surgery but refused).

Stapfer Type I perforations Endoscopic closure: Clinical success rate: 94% (17 out of 18) TTS clips: max perforation diameter 13mm TTS clips + endoloop: 30mm OTSC: 28mm Reported case of successful therapeutic ERCP following treatment with OTSC for duodenal perforation from EUS 1) For Stapfer type 1 perforations, endoscopic closure should be tried if immediately discovered. 2) If there is delayed recognition, CT should be done. The main point being surgery is indicated if there is intra-abdominal fluid or extravasation. Free air alone may warrant trial of non-surgical management. ----------------------