- Email: [email protected]
EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP
Accepted Manuscript EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP Claudia F. Consiglieri, MD, Joan B. Gornals, MD, PhD, Gino Albines, MD, Meritxell de-la-hera, Lluis Secanella, MD, Nuria Pelaez, MD, PhD, Juli Busquets, MD, PhD PII:
S0016-5107(15)03207-1
DOI:
10.1016/j.gie.2015.12.013
Reference:
YMGE 9731
To appear in:
Gastrointestinal Endoscopy
Received Date: 30 September 2015 Accepted Date: 5 December 2015
Please cite this article as: Consiglieri CF, Gornals JB, Albines G, de-la-hera M, Secanella L, Pelaez N, Busquets J, EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP, Gastrointestinal Endoscopy (2016), doi: 10.1016/j.gie.2015.12.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT COVER PAGE Title: EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP
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Authors: Claudia F Consiglieri MD (1); Joan B Gornals MD, PhD (1); Gino Albines MD (1); Meritxell de-la-hera (1); Lluis Secanella MD (2); Nuria Pelaez MD, PhD (2); Juli Busquets MD, PhD (2).
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1. Endoscopy Unit, Department of Digestive Diseases, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Catalonia, Spain
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2. General and Digestive Surgery Department, Hospital Universitari de BellvitgeIDIBELL, Barcelona, Catalonia, Spain.
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Corresponding author:
Joan B. Gornals M.D, PhD
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Endoscopy Unit, Dept. of Digestive Diseases Hospital Universitari de Bellvitge-IDIBELL (Bellvitge Biomedical Research Institute) Feixa Llarga s/n 08907 L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain Tel: +34 93 260 7682 Fax: +34 93 260 76 81 Email: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT Background and aims: When ERCP fails, EUS-guided interventional techniques may be an alternative. The aim of this study was to evaluate the general outcomes and safety of EUS-guided methylene blue cholangiopancreatography in patients with failed ERCP in benign biliopancreatic diseases.
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Methods: Patients with benign biliopancreatic diseases and failed ERCP were
included. First, EUS-guided cholangiopancreatography plus injection of methylene
blue, and second, ERCP using coloring agent flow as an indicator of papilla orifice,
were performed. Procedures were prospectively collected in this observational, single-
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center study. Technical success, clinical success, and adverse events were analyzed retrospectively.
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Results: A total of 11 patients were included (10 choledocholithiasis, 1 pancreatic stricture). The main reason for failed ERCP was an unidentifiable papilla. EUS-guided ductal access with cholangiopancreatography and papilla orifice identification was obtained in all cases. Technical success and clinical success rates of 91% were achieved, with successful biliopancreatic drainage in 10 patients. Adverse events included one peripancreatic abscess attributed to a precut, which was successfully
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treated. No adverse events were related to the first EUS-guided stage. Conclusion: EUS-guided cholangiopancreatography with methylene blue injection seems to be a feasible and helpful technique for treatment in patients with benign
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biliopancreatic diseases with previous failed ERCP due to an undetectable papilla.
INTRODUCTION
The use of methylene-blue (MB) as an indicator of the pancreatic or bile ducts
has been described in sporadic clinical cases of failed pancreatic duct (PD) cannulation [1,2]. In seeking to improve our results and simplify the technique of EUS-guided biliary drainage (EUS-BD), the purpose of this study was to evaluate the general outcomes of EUS-guided MB injection for obtaining a cholangiopancreatography and papilla identification, in patients with failed ERCP due to unidentifiable papilla and with benign biliopancreatic diseases. ERCP was attempted using the MB flow as an indicator of the papilla orifice.
ACCEPTED MANUSCRIPT METHODS Between April 2012 and January 2015, all consecutive patients were prospectively recruited and analyzed retrospectively. All procedures were performed by a single interventional endoscopist (J.G.) who annually performs more than 400 ERCPs and 500 EUS (including more than 120 EUS-guided FNA), and has done more
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than 100 EUS-guided therapeutical procedures including EUS-guided BD. Written informed consent was obtained from all patients. Our institutional review board
approved the technique. All patients with benign biliopancreatic diseases in whom
ERCP transpapillary drainage had failed due unidentifiable papilla were considered for this study. The exclusion criteria were malignant biliopancreatic diseases, non-
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accessible papilla, severe coagulopathy, age younger than 18 years, and inability to
Procedural technique (Figs.1-3)
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give written informed consent.
EUS-session: The common bile duct (CBD) or PD was imaged from the gastric and duodenum wall. The puncture was carried out using mostly a 22-gauge needle. First, bile or pancreatic juice was aspirated to confirm the intraductal location. Second, contrast medium was injected under fluoroscopic guidance to obtain a ductography. Finally, a sufficient amount (5-15 mL) of MB and saline solution (1:9 mL) was injected
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depending on duct diameter and the presence of contrast fluid flow into the small intestine monitored by fluoroscopy.
ERCP-session: If EUS-guided cholangiopancreatography was successful, the
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echoendoscope (GF-UCT140-AL5; Olympus) was withdrawn, and ERCP was immediately attempted. Papilla orifice identification was achieved using MB flow, and also thanks to a volume effect giving an image bulge. Once the papilla was reached, a
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sphincterotome (3.9F or 4.4F, AutotomeRX, Boston Scientific), with a 0.025 or 0.035inch guidewire (Visiglide;Olympus or Jagwire; Boston Scientific) was first used for direct cannulation. Second, a precut with needle-knife (microtome; Boston Scientific) was attempted. after several attempts (3-4) cannulation was not achieved, the papilla orifice was marked using a clip, and a second ERCP session was done. If necessary, papilloplasty was performed. Finally, in accordance with findings, a stent was considered. Technical success was defined as access to the CBD or PD, identification of the papilla orifice, transpapillary deep cannulation, and optimal drainage of the contrast
ACCEPTED MANUSCRIPT or fluids. Clinical success was defined as resolution of the symptoms and normalization of biocheminal parameters. Safety was defined as the rate of adverse events. All patients were monitored and admitted to our center for observation. Patient follow-up was based on outpatient examination findings, and data were collected prospectively.
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RESULTS General outcomes are summarized in Table1. A total of 2376 ERCPs were
performed during the study period. Excluding ERCPs with previous biliary intervention, a total of 1292 native papilla ERCPs were performed. The overall ERCP failure rate
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was 2.3% (30/1292). Eleven of them, 0.8% (11/1292) with undetectable papilla, were included consecutively in this study. The other failed cases were candidates for another type of EUS-guided biliary drainage or percutaneous transhepatic drainage. Number of
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previous failed ERCP was 1 to 3. In 4 patients, there was a previous failed rendezvous. The mean combined-procedure duration was 57.4 minutes. EUS-guided ductal access obtaining ductography and papilla orifice identification was successful in all patients. Technical success and clinical success rates of 91% were achieved, with successful biliopancreatic drainage in 10 patients. Eight cases were done with a single session of EUS-guided cholangiopancreatography with MB and 1 ERCP attempt; and in 3 cases a
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deep cannulation necessitated a second ERCP attempt. Adverse events related to the procedure occurred in one patient. It was a peripancreatic abscess, attributed to a precut and anticoagulation therapy, which was
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successfully treated. No adverse events were related to the first EUS-guided stage. During follow-up (range 6 to 38 months), 2 deaths were identified, but these were not
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procedure-related.
DISCUSSION
This study is the first to specifically examine the efficacy and safety of MB
injection for obtaining a cholangiopancreatography and identification of the OP in benign biliopancreatic cases with previous failed ERCP due to unidentifiable OP. Today, EUS-BD procedures enjoy a high level of technical and clinical success (91% and 88%, respectively) in expert hands, and they have been established as a real option in failed ERCP [3]. However, the mean overall adverse event rate is still considerable (26%) with a 0.4% mortality rate. In cases of benign biliopancreatic
ACCEPTED MANUSCRIPT diseases with previous failed ERCP, percutaneous transhepatic biliary drainage is commonly used as an alternative approach. However, in experienced centers, EUSguided rendezvous technique is routinely recommended first instead of direct transluminal stenting, because it is less invasive, and final drainage will be transpapillary [3,4]. Nevertheless, this technique is a labor-intensive procedure. It can fail even in expert hands, especially when the guidewire passage across the papilla is
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unsuccessful, and training programs are recommended [5-7]. In a multicenter
retrospective study, technical success was 68.3% with an adverse event rate of 21.6%, and intraductal manipulation of the guidewire was the most difficult stage[8].
With the purpose of seeking to simplify the technique of EUS-BD intervention,
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and thereby improving our outcomes, procedure-time, and safety, we decided to
replace the use of a guidewire with the use of MB [9]. This dye has been described
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before in the EUS field for tattooing small pancreatic tumors and for identifying the papilla minor or PD orifice in sporadic clinical cases [10-12]. Only 2 cases of EUSguided cholangiography using MB have been found, in a conference communication [13]. Barkay et al reported 21 patients with failed PD cannulation at ERCP. MB alone was used in 6 cases and the rendezvous technique was attempted in the rest of the cases. Success rate was 48% and in most cases the papilla was identified but a PD
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stricture did not allow deep cannulation [2].
However, in our study all of the patients had failed ERCP due to an unidentifiable or invisible papilla. Moreover, ductal access and papilla orifice detection were possible in all patients, and the overall rate of successful drainage was 91%. The
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failed case was an elderly patient and non-surgery candidate in whom no other endoscopic attempts were considered. The most difficult part of the procedure was the papillary cannulation that requires good ERCP technique. But this is made easier by
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the ductogram map and the “pregnant” effect of the papilla after EUS injection, as in a “parallel” rendezvous. No adverse events were related to the EUS-part of the intervention, and the only adverse event was attributed to a precut and anticoagulation therapy in an undetectable papilla case with altered anatomy. In our opinion, this technique is technically easier, and less demanding and time-consuming, than rendezvous [9]. In the EUS-stage, only one 22G needle is necessary, and no guidewire is required. In our experience, in the event of not achieving deep cannulation, it was helpful to mark the papilla orifice with a clip as a marker, and then to perform a second ERCP, which yielded successful results in 3
ACCEPTED MANUSCRIPT cases. In the other cases the entire procedure was done in a single session. In case of failure, other EUS-guided options such as rendezvous are not contraindicated. However, there are some limitations to this study, especially the small sample size. Considerable experience in EUS-guided puncture is mandatory, especially if ducts are not dilated enough, and the optimal amount of MB is unknown. Finally, the
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operator needs to have sufficient experience in ERCP technique, including precut sphincterotomy. It is important to note that our failure rate in native papilla ERCPs
during the study period was 2.3%, similar to the 1.7% reported recently by Holt et al [14], which implies high quality of ERCP technique, and the scenario of an
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undetectable papilla is not common.
In conclusion, our preliminary data suggest that EUS-guided
cholangiopancreatography with MB seems to be feasible, effective, and safe in
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selected patients with benign biliopancreatic diseases in whom previous ERCP failed due to an undetectable papilla. This technique may be considered before attempting other EUS-guided BD options, or after these have failed. REFERENCES:
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1. Dewitt J, McHenry L, Fogel E, et al. EUS-guided methylene blue pancreatography for minor papilla localization after unsuccessful ERCP. Gastrointest Endosc 2004;59:133-6 2. Barkay O, Sherman S, McHenry L, et al, Therapeutic EUS-assisted endoscopic retrograde pancreatography after failed pancreatic duct cannulation at ERCP. Gastrointest Endosc 2010;71:1166-73
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3. Fabbri C, Luigiano C, Lisotti A, et al. Endoscopic ultrasound-guided treatments: Are we getting evidence based-a systematic review. World J Gastroenterol 2014; 20: 8424–48
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4. Ogura T, Higuchi K. Does endoscopic ultrasound-guided biliary drainage really have clinical impact? World J Gastroenterol 2015;21:1049-52 5. Dhir V, Itoi T, Fockens P, et al. Novel ex vivo model for hands-on teaching of and training in EUS-guided biliary drainage: creation of "MumbaiEUS" stereolithography/3D printing bile duct prototype. Gastrointest Endosc 2015;81:440-6
6. Holt BA, Hawes R, Hasan M, et al. Biliary drainage: role of EUS guidance. Gastrointest Endosc. 2015 Jul 24 7. Poincloux L, Rouquette O, Buc E, et al. Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center. Endoscopy 2015;47:794-801 8. Vila JJ, Pérez-Miranda M, Vazquez-Sequeiros E, et al. Initial experience with EUSguided cholangiopancreatography for biliary and pancreatic duct drainage: a Spanish national survey. Gastrointest Endosc 2012;76:1133-41
ACCEPTED MANUSCRIPT 9. Gornals JB, Moreno R, Castellote J, et al. Single-session endosonography and endoscopic retrograde cholangiopancreatography for biliopancreatic diseases is feasible, effective and cost beneficial. Dig Liv Dis 2013;45:578-83 10. Zografos GN, Stathopoulou A, Mitropapas G, et al. Preoperative imaging and localization of small sized insulinoma with EUS-guided fine needle tattooing: a case report. Hormones (Athens). 2005;4:111-6
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11. Park SH, de Bellis M, McHenry L, et al, Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003;57:358-63
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12. Carrara S, Arcidiacono PG, Diellou AM, et al, EUS-guided methylene blue injection into the pancreatic duct as a guide for pancreatic stenting after ampullectomy. Endoscopy 2007;39:E151-2
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13. Perez-Miranda M, Gil-Simon P, De-la-Serna C, et al. EUS-Guided methylene-blue cholangiography. Gastrointest Endosc 2012;75:AB109. 14. Holt BA, Hawes R, Hasan M, et al. Biliary drainage: role of EUS guidance. Gastrointest Endosc. 2015, EPub Jul 24. doi: 10.1016/j.gie.2015.06.019.
FIGURE LEGENDS:
Figure 1: A, Endoscopic image of a periampullary diverticulum and undetectable orifice
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papilla; B, EUS-guided biliary access using a 22G needle; C, methylene blue flow is identified coming from the major papilla orifice; D, attempt at biliary cannulation with a sphincterotome (patient no. 5).
Figure 2: A, Image of an invisible papilla area; B, Endosonography-guided puncture of
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the common bile duct; C, cholangiogram obtained with the echoendoscope; D, papilla becomes visible with methylene blue coming from the duodenal wall, and is directly
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cannulated; E, completed cholangiogram via ERCP (patient no. 10). Figure 3: A, Endosonography images of choledocholithiasis in a non-dilated bile duct; B, cholangiogram obtained by EUS guidance; C, methylene blue coming from a diverticulum endoscopic image; D, biliary cannulation is attempted with a sphincterotome; E, cholangiogram via ERCP; F, extraction of white stone with an extractor balloon (patient no. 11).
ACCEPTED MANUSCRIPT
Access route
Needle, gauges
Previous failed rendezvous
Endotherapy of ERCP
Duration (minutes)
Successful procedure outcome
Adverse events Follow-up Final status (months)
88/F
Chol, CBD stones
Arterial hypertension, Alzheimer's disease
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
No
Precut sphincterotomy, no cannulation
100
No
None
16
Non-resolution Exitus (severe cholangitis)
2
71/F
Chol, CBD stones
Arterial hypertension
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
19
Yes
Precut sphincterotomy, CBD stricture, metallic stent
65
Yes
None
32
Resolution Alive
3
88/M
Chol, CBD stones
Epilepsy, COPD, congestive heart failure, atrial fibrillation with antiplatelet therapy
Previous surgery (Billroth I), undetectable papilla
Transgastric
19
Yes
Precut sphincterotomy, Biliary stent
60
Yes
None
38
Resolution Alive
4
69/M
Chol, CBD stones
Diabetes Mellitus type 2
Periampullary diverticulum, unidentifiable orifice papilla
Transgastric
22
No
Precut sphincterotomy, cleaning of CBD
50
Yes
None
38
Resolution Alive
5
67/M
Chol, CBD stones
Lung cancer
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
No
Precut sphincterotomy cleaning of CBD
55
Yes
None
17
Resolution Exitus (Pulmonary cancer)
6
36/M
AP, Chronic alcoholic pancreatitis Benign PS
Anatomic alteration, undetectable papilla
Transgastric
19/ 22
Yes
Precut sphincterotomy, 55 PD cannulation, papiloplasty, cleaning of CBD, biliary stent
Yes
None
31
Resolution Alive
7
70/M
Chol., CBD stones
Arterial hypertension, Alzheimer's disease, ischemic stroke with antiplatelet therapy
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
Yes
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
55
Yes
None
20
Resolution Alive
8
62/M
Chol., CBD stones
Diabetes Mellitus type 2, COPD
Periampullary diverticulum, unidentifiable orifice papila
22
No
Direct cannulation, papiloplasty, partial cleaning of CBD, biliary stent
40
Yes
None
14
Resolution Alive
9
77/F
AP, Chol., CBD stones
Liver transplant with immunosuppression therapy
Undetectable, Invisible papilla
Transduodenal
22
No
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
44
Yes
None
10
Resolution Alive
10
69/M
Chol., CBD stones
Arterial hypertension, Diabetes Previous surgery, Mellitus type 2, COPD, myocardial Undetectable papilla infarction with antiplatelet therapy
Transduodenal
22
No
Direct cannulation, papiloplasty, partial cleaning of CBD, biliary stent
43
Yes
None
7
Resolution Alive
11
66/M
Chol., CBD stones
Congestive heart failure, atrial fibrillation with anticoagulation therapy
Transduodenal
22
No
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
65
Yes
Abscess (treated 6 with antibiotics and percutaneous drainage)
Resolution Alive
Transduodenal
Periampullary diverticulum Previous surgery (Billroth II), undetectable papilla
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1
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Indication Comorbidities
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Age/ sex
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Patient no.
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Reason for failed ERCP
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TABLE1: Characteristics of patients, procedure details and clinical outcomes
AP, acute pancreatitis; CBD, common bile duct; Chol., Cholangitis; COPD, Chronic Obstructive Pulmonary Disease; F, female; M, Male; PD, pancreatic duct; PS pancreatic stricture.
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ACCEPTED MANUSCRIPT List of acronyms: BD: biliary drainage CBD: common bile duct MB: methylene blue
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PD: pancreatic duct
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Title: EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP Authors’ contributions:
drafting of the article, critical revision, and final approval
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Claudia F Consiglieri – conception and design, analysis and interpretation of the data,
Joan B Gornals – conception and design, analysis and interpretation of the data, drafting of the article, critical revision, and final approval Gino Albines – analysis and interpretation of the data
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Meritxell de-la-hera – analysis and interpretation of the data, final approval
Lluis Secanella – analysis and interpretation of the data, critical revision final approval Nuria Pelaez – analysis and interpretation of the data, critical revision, final approval
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Juli Busquets – critical revision, final approval
S0016-5107(15)03207-1
DOI:
10.1016/j.gie.2015.12.013
Reference:
YMGE 9731
To appear in:
Gastrointestinal Endoscopy
Received Date: 30 September 2015 Accepted Date: 5 December 2015
Please cite this article as: Consiglieri CF, Gornals JB, Albines G, de-la-hera M, Secanella L, Pelaez N, Busquets J, EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP, Gastrointestinal Endoscopy (2016), doi: 10.1016/j.gie.2015.12.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT COVER PAGE Title: EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP
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Authors: Claudia F Consiglieri MD (1); Joan B Gornals MD, PhD (1); Gino Albines MD (1); Meritxell de-la-hera (1); Lluis Secanella MD (2); Nuria Pelaez MD, PhD (2); Juli Busquets MD, PhD (2).
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1. Endoscopy Unit, Department of Digestive Diseases, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Catalonia, Spain
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2. General and Digestive Surgery Department, Hospital Universitari de BellvitgeIDIBELL, Barcelona, Catalonia, Spain.
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Corresponding author:
Joan B. Gornals M.D, PhD
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Endoscopy Unit, Dept. of Digestive Diseases Hospital Universitari de Bellvitge-IDIBELL (Bellvitge Biomedical Research Institute) Feixa Llarga s/n 08907 L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain Tel: +34 93 260 7682 Fax: +34 93 260 76 81 Email: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT Background and aims: When ERCP fails, EUS-guided interventional techniques may be an alternative. The aim of this study was to evaluate the general outcomes and safety of EUS-guided methylene blue cholangiopancreatography in patients with failed ERCP in benign biliopancreatic diseases.
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Methods: Patients with benign biliopancreatic diseases and failed ERCP were
included. First, EUS-guided cholangiopancreatography plus injection of methylene
blue, and second, ERCP using coloring agent flow as an indicator of papilla orifice,
were performed. Procedures were prospectively collected in this observational, single-
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center study. Technical success, clinical success, and adverse events were analyzed retrospectively.
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Results: A total of 11 patients were included (10 choledocholithiasis, 1 pancreatic stricture). The main reason for failed ERCP was an unidentifiable papilla. EUS-guided ductal access with cholangiopancreatography and papilla orifice identification was obtained in all cases. Technical success and clinical success rates of 91% were achieved, with successful biliopancreatic drainage in 10 patients. Adverse events included one peripancreatic abscess attributed to a precut, which was successfully
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treated. No adverse events were related to the first EUS-guided stage. Conclusion: EUS-guided cholangiopancreatography with methylene blue injection seems to be a feasible and helpful technique for treatment in patients with benign
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biliopancreatic diseases with previous failed ERCP due to an undetectable papilla.
INTRODUCTION
The use of methylene-blue (MB) as an indicator of the pancreatic or bile ducts
has been described in sporadic clinical cases of failed pancreatic duct (PD) cannulation [1,2]. In seeking to improve our results and simplify the technique of EUS-guided biliary drainage (EUS-BD), the purpose of this study was to evaluate the general outcomes of EUS-guided MB injection for obtaining a cholangiopancreatography and papilla identification, in patients with failed ERCP due to unidentifiable papilla and with benign biliopancreatic diseases. ERCP was attempted using the MB flow as an indicator of the papilla orifice.
ACCEPTED MANUSCRIPT METHODS Between April 2012 and January 2015, all consecutive patients were prospectively recruited and analyzed retrospectively. All procedures were performed by a single interventional endoscopist (J.G.) who annually performs more than 400 ERCPs and 500 EUS (including more than 120 EUS-guided FNA), and has done more
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than 100 EUS-guided therapeutical procedures including EUS-guided BD. Written informed consent was obtained from all patients. Our institutional review board
approved the technique. All patients with benign biliopancreatic diseases in whom
ERCP transpapillary drainage had failed due unidentifiable papilla were considered for this study. The exclusion criteria were malignant biliopancreatic diseases, non-
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accessible papilla, severe coagulopathy, age younger than 18 years, and inability to
Procedural technique (Figs.1-3)
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give written informed consent.
EUS-session: The common bile duct (CBD) or PD was imaged from the gastric and duodenum wall. The puncture was carried out using mostly a 22-gauge needle. First, bile or pancreatic juice was aspirated to confirm the intraductal location. Second, contrast medium was injected under fluoroscopic guidance to obtain a ductography. Finally, a sufficient amount (5-15 mL) of MB and saline solution (1:9 mL) was injected
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depending on duct diameter and the presence of contrast fluid flow into the small intestine monitored by fluoroscopy.
ERCP-session: If EUS-guided cholangiopancreatography was successful, the
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echoendoscope (GF-UCT140-AL5; Olympus) was withdrawn, and ERCP was immediately attempted. Papilla orifice identification was achieved using MB flow, and also thanks to a volume effect giving an image bulge. Once the papilla was reached, a
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sphincterotome (3.9F or 4.4F, AutotomeRX, Boston Scientific), with a 0.025 or 0.035inch guidewire (Visiglide;Olympus or Jagwire; Boston Scientific) was first used for direct cannulation. Second, a precut with needle-knife (microtome; Boston Scientific) was attempted. after several attempts (3-4) cannulation was not achieved, the papilla orifice was marked using a clip, and a second ERCP session was done. If necessary, papilloplasty was performed. Finally, in accordance with findings, a stent was considered. Technical success was defined as access to the CBD or PD, identification of the papilla orifice, transpapillary deep cannulation, and optimal drainage of the contrast
ACCEPTED MANUSCRIPT or fluids. Clinical success was defined as resolution of the symptoms and normalization of biocheminal parameters. Safety was defined as the rate of adverse events. All patients were monitored and admitted to our center for observation. Patient follow-up was based on outpatient examination findings, and data were collected prospectively.
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RESULTS General outcomes are summarized in Table1. A total of 2376 ERCPs were
performed during the study period. Excluding ERCPs with previous biliary intervention, a total of 1292 native papilla ERCPs were performed. The overall ERCP failure rate
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was 2.3% (30/1292). Eleven of them, 0.8% (11/1292) with undetectable papilla, were included consecutively in this study. The other failed cases were candidates for another type of EUS-guided biliary drainage or percutaneous transhepatic drainage. Number of
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previous failed ERCP was 1 to 3. In 4 patients, there was a previous failed rendezvous. The mean combined-procedure duration was 57.4 minutes. EUS-guided ductal access obtaining ductography and papilla orifice identification was successful in all patients. Technical success and clinical success rates of 91% were achieved, with successful biliopancreatic drainage in 10 patients. Eight cases were done with a single session of EUS-guided cholangiopancreatography with MB and 1 ERCP attempt; and in 3 cases a
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deep cannulation necessitated a second ERCP attempt. Adverse events related to the procedure occurred in one patient. It was a peripancreatic abscess, attributed to a precut and anticoagulation therapy, which was
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successfully treated. No adverse events were related to the first EUS-guided stage. During follow-up (range 6 to 38 months), 2 deaths were identified, but these were not
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procedure-related.
DISCUSSION
This study is the first to specifically examine the efficacy and safety of MB
injection for obtaining a cholangiopancreatography and identification of the OP in benign biliopancreatic cases with previous failed ERCP due to unidentifiable OP. Today, EUS-BD procedures enjoy a high level of technical and clinical success (91% and 88%, respectively) in expert hands, and they have been established as a real option in failed ERCP [3]. However, the mean overall adverse event rate is still considerable (26%) with a 0.4% mortality rate. In cases of benign biliopancreatic
ACCEPTED MANUSCRIPT diseases with previous failed ERCP, percutaneous transhepatic biliary drainage is commonly used as an alternative approach. However, in experienced centers, EUSguided rendezvous technique is routinely recommended first instead of direct transluminal stenting, because it is less invasive, and final drainage will be transpapillary [3,4]. Nevertheless, this technique is a labor-intensive procedure. It can fail even in expert hands, especially when the guidewire passage across the papilla is
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unsuccessful, and training programs are recommended [5-7]. In a multicenter
retrospective study, technical success was 68.3% with an adverse event rate of 21.6%, and intraductal manipulation of the guidewire was the most difficult stage[8].
With the purpose of seeking to simplify the technique of EUS-BD intervention,
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and thereby improving our outcomes, procedure-time, and safety, we decided to
replace the use of a guidewire with the use of MB [9]. This dye has been described
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before in the EUS field for tattooing small pancreatic tumors and for identifying the papilla minor or PD orifice in sporadic clinical cases [10-12]. Only 2 cases of EUSguided cholangiography using MB have been found, in a conference communication [13]. Barkay et al reported 21 patients with failed PD cannulation at ERCP. MB alone was used in 6 cases and the rendezvous technique was attempted in the rest of the cases. Success rate was 48% and in most cases the papilla was identified but a PD
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stricture did not allow deep cannulation [2].
However, in our study all of the patients had failed ERCP due to an unidentifiable or invisible papilla. Moreover, ductal access and papilla orifice detection were possible in all patients, and the overall rate of successful drainage was 91%. The
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failed case was an elderly patient and non-surgery candidate in whom no other endoscopic attempts were considered. The most difficult part of the procedure was the papillary cannulation that requires good ERCP technique. But this is made easier by
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the ductogram map and the “pregnant” effect of the papilla after EUS injection, as in a “parallel” rendezvous. No adverse events were related to the EUS-part of the intervention, and the only adverse event was attributed to a precut and anticoagulation therapy in an undetectable papilla case with altered anatomy. In our opinion, this technique is technically easier, and less demanding and time-consuming, than rendezvous [9]. In the EUS-stage, only one 22G needle is necessary, and no guidewire is required. In our experience, in the event of not achieving deep cannulation, it was helpful to mark the papilla orifice with a clip as a marker, and then to perform a second ERCP, which yielded successful results in 3
ACCEPTED MANUSCRIPT cases. In the other cases the entire procedure was done in a single session. In case of failure, other EUS-guided options such as rendezvous are not contraindicated. However, there are some limitations to this study, especially the small sample size. Considerable experience in EUS-guided puncture is mandatory, especially if ducts are not dilated enough, and the optimal amount of MB is unknown. Finally, the
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operator needs to have sufficient experience in ERCP technique, including precut sphincterotomy. It is important to note that our failure rate in native papilla ERCPs
during the study period was 2.3%, similar to the 1.7% reported recently by Holt et al [14], which implies high quality of ERCP technique, and the scenario of an
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undetectable papilla is not common.
In conclusion, our preliminary data suggest that EUS-guided
cholangiopancreatography with MB seems to be feasible, effective, and safe in
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selected patients with benign biliopancreatic diseases in whom previous ERCP failed due to an undetectable papilla. This technique may be considered before attempting other EUS-guided BD options, or after these have failed. REFERENCES:
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1. Dewitt J, McHenry L, Fogel E, et al. EUS-guided methylene blue pancreatography for minor papilla localization after unsuccessful ERCP. Gastrointest Endosc 2004;59:133-6 2. Barkay O, Sherman S, McHenry L, et al, Therapeutic EUS-assisted endoscopic retrograde pancreatography after failed pancreatic duct cannulation at ERCP. Gastrointest Endosc 2010;71:1166-73
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3. Fabbri C, Luigiano C, Lisotti A, et al. Endoscopic ultrasound-guided treatments: Are we getting evidence based-a systematic review. World J Gastroenterol 2014; 20: 8424–48
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4. Ogura T, Higuchi K. Does endoscopic ultrasound-guided biliary drainage really have clinical impact? World J Gastroenterol 2015;21:1049-52 5. Dhir V, Itoi T, Fockens P, et al. Novel ex vivo model for hands-on teaching of and training in EUS-guided biliary drainage: creation of "MumbaiEUS" stereolithography/3D printing bile duct prototype. Gastrointest Endosc 2015;81:440-6
6. Holt BA, Hawes R, Hasan M, et al. Biliary drainage: role of EUS guidance. Gastrointest Endosc. 2015 Jul 24 7. Poincloux L, Rouquette O, Buc E, et al. Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center. Endoscopy 2015;47:794-801 8. Vila JJ, Pérez-Miranda M, Vazquez-Sequeiros E, et al. Initial experience with EUSguided cholangiopancreatography for biliary and pancreatic duct drainage: a Spanish national survey. Gastrointest Endosc 2012;76:1133-41
ACCEPTED MANUSCRIPT 9. Gornals JB, Moreno R, Castellote J, et al. Single-session endosonography and endoscopic retrograde cholangiopancreatography for biliopancreatic diseases is feasible, effective and cost beneficial. Dig Liv Dis 2013;45:578-83 10. Zografos GN, Stathopoulou A, Mitropapas G, et al. Preoperative imaging and localization of small sized insulinoma with EUS-guided fine needle tattooing: a case report. Hormones (Athens). 2005;4:111-6
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11. Park SH, de Bellis M, McHenry L, et al, Use of methylene blue to identify the minor papilla or its orifice in patients with pancreas divisum. Gastrointest Endosc 2003;57:358-63
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12. Carrara S, Arcidiacono PG, Diellou AM, et al, EUS-guided methylene blue injection into the pancreatic duct as a guide for pancreatic stenting after ampullectomy. Endoscopy 2007;39:E151-2
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13. Perez-Miranda M, Gil-Simon P, De-la-Serna C, et al. EUS-Guided methylene-blue cholangiography. Gastrointest Endosc 2012;75:AB109. 14. Holt BA, Hawes R, Hasan M, et al. Biliary drainage: role of EUS guidance. Gastrointest Endosc. 2015, EPub Jul 24. doi: 10.1016/j.gie.2015.06.019.
FIGURE LEGENDS:
Figure 1: A, Endoscopic image of a periampullary diverticulum and undetectable orifice
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papilla; B, EUS-guided biliary access using a 22G needle; C, methylene blue flow is identified coming from the major papilla orifice; D, attempt at biliary cannulation with a sphincterotome (patient no. 5).
Figure 2: A, Image of an invisible papilla area; B, Endosonography-guided puncture of
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the common bile duct; C, cholangiogram obtained with the echoendoscope; D, papilla becomes visible with methylene blue coming from the duodenal wall, and is directly
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cannulated; E, completed cholangiogram via ERCP (patient no. 10). Figure 3: A, Endosonography images of choledocholithiasis in a non-dilated bile duct; B, cholangiogram obtained by EUS guidance; C, methylene blue coming from a diverticulum endoscopic image; D, biliary cannulation is attempted with a sphincterotome; E, cholangiogram via ERCP; F, extraction of white stone with an extractor balloon (patient no. 11).
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Access route
Needle, gauges
Previous failed rendezvous
Endotherapy of ERCP
Duration (minutes)
Successful procedure outcome
Adverse events Follow-up Final status (months)
88/F
Chol, CBD stones
Arterial hypertension, Alzheimer's disease
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
No
Precut sphincterotomy, no cannulation
100
No
None
16
Non-resolution Exitus (severe cholangitis)
2
71/F
Chol, CBD stones
Arterial hypertension
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
19
Yes
Precut sphincterotomy, CBD stricture, metallic stent
65
Yes
None
32
Resolution Alive
3
88/M
Chol, CBD stones
Epilepsy, COPD, congestive heart failure, atrial fibrillation with antiplatelet therapy
Previous surgery (Billroth I), undetectable papilla
Transgastric
19
Yes
Precut sphincterotomy, Biliary stent
60
Yes
None
38
Resolution Alive
4
69/M
Chol, CBD stones
Diabetes Mellitus type 2
Periampullary diverticulum, unidentifiable orifice papilla
Transgastric
22
No
Precut sphincterotomy, cleaning of CBD
50
Yes
None
38
Resolution Alive
5
67/M
Chol, CBD stones
Lung cancer
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
No
Precut sphincterotomy cleaning of CBD
55
Yes
None
17
Resolution Exitus (Pulmonary cancer)
6
36/M
AP, Chronic alcoholic pancreatitis Benign PS
Anatomic alteration, undetectable papilla
Transgastric
19/ 22
Yes
Precut sphincterotomy, 55 PD cannulation, papiloplasty, cleaning of CBD, biliary stent
Yes
None
31
Resolution Alive
7
70/M
Chol., CBD stones
Arterial hypertension, Alzheimer's disease, ischemic stroke with antiplatelet therapy
Periampullary diverticulum, unidentifiable orifice papilla
Transduodenal
22
Yes
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
55
Yes
None
20
Resolution Alive
8
62/M
Chol., CBD stones
Diabetes Mellitus type 2, COPD
Periampullary diverticulum, unidentifiable orifice papila
22
No
Direct cannulation, papiloplasty, partial cleaning of CBD, biliary stent
40
Yes
None
14
Resolution Alive
9
77/F
AP, Chol., CBD stones
Liver transplant with immunosuppression therapy
Undetectable, Invisible papilla
Transduodenal
22
No
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
44
Yes
None
10
Resolution Alive
10
69/M
Chol., CBD stones
Arterial hypertension, Diabetes Previous surgery, Mellitus type 2, COPD, myocardial Undetectable papilla infarction with antiplatelet therapy
Transduodenal
22
No
Direct cannulation, papiloplasty, partial cleaning of CBD, biliary stent
43
Yes
None
7
Resolution Alive
11
66/M
Chol., CBD stones
Congestive heart failure, atrial fibrillation with anticoagulation therapy
Transduodenal
22
No
Precut sphincterotomy, papiloplasty, partial cleaning of CBD, biliary stent
65
Yes
Abscess (treated 6 with antibiotics and percutaneous drainage)
Resolution Alive
Transduodenal
Periampullary diverticulum Previous surgery (Billroth II), undetectable papilla
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1
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Indication Comorbidities
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Age/ sex
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Patient no.
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Reason for failed ERCP
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TABLE1: Characteristics of patients, procedure details and clinical outcomes
AP, acute pancreatitis; CBD, common bile duct; Chol., Cholangitis; COPD, Chronic Obstructive Pulmonary Disease; F, female; M, Male; PD, pancreatic duct; PS pancreatic stricture.
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SC
RI PT
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EP
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M AN U
SC
RI PT
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AC C
EP
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M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
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M AN U
SC
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ACCEPTED MANUSCRIPT List of acronyms: BD: biliary drainage CBD: common bile duct MB: methylene blue
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PD: pancreatic duct
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Title: EUS-guided methylene blue cholangiopancreatography for benign biliopancreatic diseases after failed ERCP Authors’ contributions:
drafting of the article, critical revision, and final approval
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Claudia F Consiglieri – conception and design, analysis and interpretation of the data,
Joan B Gornals – conception and design, analysis and interpretation of the data, drafting of the article, critical revision, and final approval Gino Albines – analysis and interpretation of the data
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Meritxell de-la-hera – analysis and interpretation of the data, final approval
Lluis Secanella – analysis and interpretation of the data, critical revision final approval Nuria Pelaez – analysis and interpretation of the data, critical revision, final approval
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Juli Busquets – critical revision, final approval