EUS- Gallbladder Drainage: is it time to replace percutaneous drainage?

Jessica Widmer, DO1, Juveria Abdullah1, Michel Kahaleh, MD.1

Division of and Hepatology, Department of Medicine, Weill Cornell

Medical College,1 New York, USA

Running title: EUS guided gallbladder drainage

Keywords: , , EUS-guided drainage, EUS-guided intervention. Cholecystoduodenostomy

Address for Correspondence:

Michel Kahaleh, MD, AGAF, FACG, FASGE Professor of Medicine Chief of Endoscopy Division of Gastroenterology & Hepatology Department of Medicine Weill Cornell Medical College 1305 York Avenue, 4th Floor New York, NY 10021 Telephone: 646-962-4000 Fax: 646-962-0110 Email: [email protected]

Abstract:

Acute cholecystitis in patients who are not suitable for surgery can benefit from EUS-

GBD to avoid percutaneous transhepatic gallbladder drainage (PT-GBD) associated with poor quality of life and increased morbidity.

The technique involves EUS guided access of the gallbladder with creation of a gastric or duodenal fistula followed by placement of a stent. The overall reported technical success rate is 87/90 (96.6%). A total of 11/90 (12.2%) patients had complications including pneumoperitoneum, bile peritonitis and stent migration.

EUS-GBD provide gallbladder drainage in situations where percutaneous or transpapillary drainage is not feasible or technically challenging, it also offer the patients a better option with improved quality of life and decreased global morbidity by avoiding percutaneous access.

Introduction:

Surgical cholecystectomy has been the mainstay of treatment for acute cholecystitis.

For patients with advanced age, comorbidities, use of anti-platelet medications, and/or the presence of advanced malignancy, gallbladder drainage has been recommended instead of surgery.[1] Techniques for non-surgical gallbladder drainage include percutaneous transhepatic gallbladder aspiration or drainage (PT-GBD) and transpapillary endoscopic gallbladder stenting.[2] Endoscopic transpapillary drainage can be technically difficult in some cases with biliary or pancreatic malignancy due to cystic duct obstruction or previously placed metal stents. The need for alternative methods of gallbladder drainage during the evolution of EUS guided drainage techniques for extraluminal collections such as pseudocysts has lead to development of

EUS guided gallbladder drainage (EUS-GBD) techniques.[3-6]

.

Materials and methods:

Echoendoscopes

Conventional curved linear array oblique viewing therapeutic echoendoscopes are typically used (GF-UCT 180, Olympus America, Melville, NY). The working channel of this scope is 3.7 mm, allowing placement of 10 mm fully covered metal stents and 10 F double pigtail stents.[7] Itoi and colleagues have also reported the use of a prototype forward view curved linear array echoendoscope, which may enable the endoscopist to overcome this issue by exerting force directly with the scope towards the target.[8]

Patient selection and preparation

Contrast enhanced abdominal CT or magnetic resonance imaging should be reviewed as a roadmap prior to endoscopic intervention. This procedure is frequently performed under general anesthesia, although conscious sedation is also used at the discretion of the endoscopist. Peri-procedural antibiotics are often administered.

EUS guided gallbladder drainage technique (Table 1)

Endoluminal puncture site

Endoscopic ultrasound is used to identify the site of initial puncture at a location where the gallbladder lies closest to the bowel lumen, avoids blood vessels and a stable position of the endoscope tip can be easily maintained. The gastric antral wall has been the preferred site for the initial puncture to access in few large case series,[9-11] while some authors report the use of a transduodenal approach with similar success rates.[8,

12] Lee and colleagues reported use of the transgastric approach to access the body of the gallbladder and the transduodenal approach for the gallbladder neck.[13] In early reports of EUS-GBD, Lee et al. and Baron et al. commented that directing the puncture needle to the gallbladder neck can be advantageous since it is less mobile and is less likely to move away from the duodenal wall.[13, 14]

Puncture needle Most reports have consistently used a 19 gauge fine needle aspiration (FNA) needle to obtain access (Figure 1). Subtil et al. have described use of a one step device

(Giovannini Needle Wire Oasis, Cook Ireland Ltd, Limerick, Ireland), which allows puncture, dilation, electrocautery, and placement of the stent in one device.[11] This system is advantageous because it reduces the time that passes from the initial needle puncture until stent deployment, which reduces the risk of loss of guidewire access and potential complications. However, this system is only available for 8.5 and 10 F straight stents.[11]

Tract dilator

After gaining access with a 0.035 inch guidewire, which is coiled into the gallbladder, the fistula tract is dilated using either a mechanical or electrocautery device (Figure 2).

A biliary dilation catheter (Soehendra, Cook Medical) has been used as the initial dilating device in many reports.[10, 13, 15-17] A triple lumen cystoenterostome (6F or

10F Cysto-Gastro Set, Endo-flex, Voerde, Germany or Cystotome, Cook Endoscopy) is another preferred dilation device, which can assist in dilation using diathermy and/or a needle knife.[15] [8-12, 16] A cystoenterostome has the advantage of performing dilation without lifting the ultrasound probe from the gut wall while diathermy causes melting of tissue and inflammatory reaction which can aid in keeping the tissue layers together. [12] Some authors have described the use of 4 mm hurricane biliary balloon dilator either alone or in tandem with the methods mentioned above to achieve adequate dilation.[8, 9]

Endoprosthesis

After tract dilation, the stent delivery system or stent followed by the pushing catheter is advanced over the wire and into the cyst. The tip of echoendoscope is then carefully lifted from the luminal wall maintaining the direction to allow visualization of the stent deployment. The distal end of stent is deployed under fluoroscopic guidance, then the proximal end is then deployed endoscopically. The stent length is determined by the combined thickness of the interposed tissue as measured by EUS (Figure 3).

Plastic biliary stents (PBS) were used in most early studies describing EUS-GBD. A variety of PBS such as double pigtail, single pigtail and straight have been used with similar success rates (Table 1). [11-13, 16-18] The insertion of a plastic stent usually requires a tract diameter slightly larger than the stent to be placed, which could lead to a gap and potential leakage. [10] Self expanding metal stents (SEMS) were used for

EUS-GBD in one case series of fifteen patients in an attempt to circumvent the limitations of PBS by sealing the gap between the stent and the fistula as the stent expands. [10] SEMS can also be repositioned if desired, avoiding the need for a second puncture. Jang and colleagues described the use of 10 mm diameter covered metal stents (BONA-AL Standard Sci Tech Inc, Seoul, Korea), which are modified with flared ends up to 22 mm to prevent migration. [10] The larger diameter of the stent lumen also decreases risk of stent occlusion. Lumen-apposing stents (AXIOS, Xlumena Inc,

Mountain View, California) are the newest development in the arena of EUS-GBD. The

AXIOS stents have a 10 mm diameter with bilateral anchor flanges, which provide lumen to lumen apposition and prevent leakage. [8] It is also possible to access the gallbladder lumen through the stent with a slim endoscope to perform biopsies, remove stones or for debridement.[8, 9, 19]

Literature Review (Table 1)

Indications for the procedures included patients with acute cholecystitis that were not suitable for surgical cholecystectomy due to malignancy or other comorbidities and/or after failed endoscopic transpapillary gallbladder stenting. The initial needle puncture was made in a transgastric fashion in 54/73 patients (74%) and transduodenally in

19/73 patients (26%). One study including 30 patients did not specify whether the puncture was performed transgastrically or transduodenally. Nasocystic drainage tubes were used in 41/103 (39.8%) patients, plastic stents were used in 16/103 (15.5%) of patients, and covered metal stents were used in 46/103 (44.6%) patients.

The overall reported technical success rate is 100/103 (97.1%). Technical failures were attributed to loss of guidewire access (n = 1), uncontrolled stent release (n = 1) and cobblestone gallbladder limiting advancement of guidewire (n = 1). Clinical success defined as improvement in clinical and laboratory parameters was achieved in 100% patients when EUS-GBD was technically successful.

A total of 11/103 (10.7%) patients had complications. Pneumoperitoneum (n = 6) was the most commonly reported complication and was self-limited in all cases. [10, 13, 15,

16] Bile peritonitis (n = 1) and stent migration (n = 1) were reported with placement of

PBS.[16] Bile peritonitis was managed conservatively. Distal stent migration was seen as a late complication at 3 weeks post-procedure and was without clinical consequence.

[16] AXIOS stents have been associated with self-limited hematochezia (n = 1), right hypochondrium pain (n = 1) and oozing at fistula site (n = 1). [8, 9] Other procedure related events reported include: transient dislodgement of cystoenterostome requiring a second puncture with a resultant small bile leak, and clogging, migration or spontaneous expulsion of stent without clinical consequences. [9, 11, 12, 15, 16]

Discussion:

Percutaneous techniques have been used for gallbladder drainage for years with good technical and clinical success rates. Risks involved with PT-GBD include liver injury secondary to puncture causing hemorrhage, pneumothorax, bile leak, dislodged tube, and skin site infections, which compromise quality of life and increase length of hospital stay. [2] PT-GBD has a complication rate ranging up to 12%[20] and issues such as catheter related pain, management of bile bag and cosmetic problems affect quality of life. [21] Most patients treated with percutaneous techniques eventually will need a cholecystectomy or acute cholecystitis can recur.[22] To overcome these limitations, there has been a need for find alternative techniques to manage patients with acute cholecystitis who are poor surgical candidates.

ET-GBD can be technically challenging in the setting of acute cholecystitis and has a risk of post-ERCP pancreatitis.[23, 24] It may not be feasible in patients with an inaccessible papilla or biliary obstruction due to malignancy. EUS-GBD can be a valuable alternative in selected patients not candidates of PT-GBD or ET-GBD. EUS-

GBD is carried out through gastric or duodenal wall, avoiding puncture of liver, which is more vascular and is safer in patients with coagulopathy or using anti-platelet agents. [7-13, 15-18] It can also be performed safely in patients with perihepatic ascites where

PT-GBD is not feasible.

The technique of EUS guided drainage has evolved over past decade with drainage of extraluminal collections such as pancreatic pseudocysts, necrosis and abscesses. [25,

26] We have previously reported drainage of bilomas and gallbladder fossa fluid collections with success. [6, 27] Baron and colleagues first reported successful EUS guided transduodenal gallbladder drainage using double pigtail PBS in a patient with and bilateral metal biliary stents. [14] Limited apposition of PBS with the tract wall lead to bile leak and stent migration[11, 16], although it has been postulated that thickened gallbladder wall and or surrounding adhesions can decrease the risk of bile leak. [13, 14] Most authors have used 7 F or 8.5 F diameter PBS which could clog due to thick drainage. [16] SEMS avoid these potential limitations of PBS by causing apposition at the tract wall to decrease chances of leakage and a have wider internal diameter that reduces the risk of clogging. Jang and colleagues described use of partially covered SEMS modified by adding flaring and angulations at the distal ends to prevent stent migration.[10] The ends of SEMS have the potential to cause injury and bleeding by abutting with the gallbladder or bowel lumen, although this has not been reported.[28] The lumen apposing AXIOS stent is another modification of SEMS by means of a “saddle” shape with distal anchor flanges to ensure both lumen apposition and drainage. Three recent case series involving 31 patients have shown reasonable success rates.[8, 9, 19] Deployment of AXIOS stents can be technically challenging, particularly in patients with a thickened gallbladder wall leading to low technical success rates in the initial pilot study. [9] These stents have been shown to provide an additional advantage of allowing access to the gallbladder lumen with slim (<10 mm) endoscope to perform biopsies, stone removal or debridement. [8, 9, 19]

Early experience with EUS-GBD procedures has shown minimal adverse events.

Pneumoperitoneum, the most common adverse event, was reported only in case series using a biliary dilation catheter for tract dilation. Due to lack of detailed information on individual cases, pneumoperitoneum cannot be clearly be attributed to biliary dilation catheters, but it has been postulated that the sheer force by the dilators has potential to detach and push away the gallbladder wall possibly leading to pneumoperitoneum.

SEMS or lumen-apposing AXIOS stents are promising since complications associated with PBS such as bile leak and stent migration have not been reported. EUS-GBD with placement of SEMS or AXIOS stent is a reasonable palliative option in patients with malignancy affecting biliary system and avoids recurrence of cholecystitis due to stent blockage or removal as seen with other techniques which use smaller diameter drains.

EUS-GBD with AXIOS can also aid in treatment of large stones by performing cholecystoscopy. [9]

In summary, EUS-GBD is an evolving alternative to PT-GBD or ET-GBD in selected patients as a bridge to surgery or for palliation. The potential to perform therapeutic maneuvers will expand its applications in future. With continued development of EUS drainage accessories and experience with the drainage techniques, EUS-GBD is likely to have better technical success rates with minimal adverse events. With the widespread adoption of EUS-GBD, the indications are likely to expand. It can potentially be an access point for therapies directed towards biliary tree or liver such as photodynamic therapy, radiofrequency ablation through a transcystic approach in patients with inaccessible ampulla due to malignancy or altered anatomy after .

Table Legend

Table 1: Summary of studies describing endoscopic ultrasound guided gallbladder drainage

Table 1: Summary of studies describing endoscopic ultrasound guided gallbladder drainage

Author/Year/lo Num Indications Initial Tract Endoprost Mean Techni Clini Length of Limitatio Complicat cation ber of puncture dilatior hesis for proced cal cal follow up ns ions cases site drainage ure success succe time rate ss (min) rate Moon et al. [19] 13 Acute Stomach 6-8F Lumen Not 100% 100% 6 months None None 2014 cholecystitis, dilating apposing reporte Korea gallbladder catheter stent d cancer, Needle (AXIOS, pancreatic fluid knife Xlumena collections 4 mm Inc, balloon Mountain catheter View, CA) 10 mm diameter Jang et al.[15] 30 Acute Stomach 6F 5 F 23 ± 7 97% 100% 221 days Loss of Pneumoperito 2012 cholecystitis or dilator nasobiliary (6 days for guide neum (2/30) Korea unsuitable for duodenal catheter drainage patients who wire Self limiting emergency wall (43.3%) tube underwent access cholecystectom (numbers Triple cholecystect y not lumen omy) specified) needle knife (56.7%) Itoi et al.[8] 5 Aute 1 stomach 4 mm Lumen 23.4 100% 100% 9 months None Mild self 2012 cholecystitis in 4 hurrican apposing limited oozing Japan non-surgical duodenum e stent along fistula candidates dilating (AXIOS, tract (3 pancreatic balloon Xlumena cancers, 1 (N=4) Inc, cholangiocarci Mountain noma 10F View, CA) 1 gallstone cystoto 10 mm disease) me diameter (N=1) (length 6mm in 4 cases and 10 mm in one case) Serna-Higuera et 13 Acute 12/13 8.5F -Lumen Not 84.6% 100% 100.81 days Thickene Hematochezia al.[9] cholecystitis in transgastri Cystoto apposing reporte d (1/11) 2012 non surgical c-antral me stent d gallbladd Right hypo- Spain candidates for 1/13 followed (AXIOS, er wall chondrium emergent transduode by 4mm Xlumena pain (1/11) cholecystectom nal hurrican Inc, Uncontrol Both self y e biliary Mountain led stent limiting balloon View, CA) release dilator -Additional fully covered SEMS within AXIOS in 4 subjects Jang et al. [10] 15 Acute 10/15 -6 or 7 F Partially Not 100% 100% 145 days None Pneumoperito 2011 Cholecystitis transgastri Soehend covered reporte neum (2/15) Korea unsuitable for c- ra SEMS 10 d Self limiting cholecystectom prepyloric biliary mm y after failed antrum dilation diameter ERCP with 5/15 catheter and 4-7 mm transpapillary transduode length cystic approach nal -Triple (Modified* lumen BONA-AL needle Stent, knife Standard microto Sci Tech me Inc, Seoul, Korea) Song et al. [16] 8 Acute 7/8 -6 or 7 F 7F double- 28 100% 100% 186 days Clogging 1 pneumo- 2010 Cholecystitis transduode tapered pigtail (range of stent peritoneum Korea poor surgical nal tip plastic stent 17-32) (no (self limiting) candidates 1/8 biliary clinical 1 bile after failed transgastri dilation conseque peritonitis transpapillary c catheter nce) 1 distal stent cystic approach migration (4 -7F cholangiocarci Triple noma, 2 liver lumen cirrhosis, 1 on needle anticoagulation knife , 1 malignant microto cystic duct me (6/8) obstruction) Subtil et al. [11] 4 Acute Transgastr -10F 8.5F stent Not 100% 100% Not reported Stent None 2010 cholecystitis ic- cystoto modified reporte migration Spain with prepyloric me (1 Cotton- d into gall perforation and antrum case) Leung® bladder perigallbladder (Amsterda abscess in non -One- m) Spontane surgical step ous stent candidates system 10F stent expulsion (1 NWOA modified Alzheimer’s, 3 (Giovan Soehendra advanced nini Tannenbau hepatobiliary Needle m Biliary malignancies) Wire Oasis (3 cases) Kamata et al. 1 Acute Transgastr Serial 6 7F X 4 cm Not 100% 100% 6 months None None [17] cholecystitis in ic Fr, 7 Fr, double reporte 2009 patient with and 9 Fr; pigtail d Japan malignant Soehend biliary ra obstruction biliary treated with dilation covered SEMS catheters Takasawa et 1 Acute Transgastr Needle 7.2 Fr, 30 Not 100% 100% 10 days None None al.[18] cholecystitis in ic knife cm-long, reporte 2009 patient with papiloto single d Japan malignant me pigtail biliary plastic tube obstruction after SEMS Kwan et al. [12] 3 Acute 1 6F or Single Not 100% 100% 6 weeks Transient None 2007 Cholecystitis in Transgastr 10F pigtail reporte dislodge Belgium non surgical ic-antral Cysto- nasocholec d ment of candidates 2 Gastro ystic drain cysto- transduode Set enterosto nal [Endo- together or me flex, followed by causing Voerde, small bile German 8.5F leak and y] Double- requiring pigtail stent repeat Cystoto (Zimmon puncture me biliary [Cook stent) endosco py] Lee et al.[13] 9 Acute 4 6F or 7F 5F 20 100% 100% 3-12 months None Pneumoperito 2007 Cholecystitis transgastri bougie nasobiliary (range neum (1/9) Korea (Gallstone c (Soehen drainage 10-35) self limiting induced) in 5 dra tube elderly or high transduode biliary risk due to co nal dilatatio morbidities or n on catheter) anticoagulation not suitable emergent cholecystectom y Baron et al.[14] 1 Acute Transduod 4 mm 7F X 4cm Not 100% 100% 11 weeks None None 2007 Cholecystitis in enal balloon double reporte USA patient with pigtail d cholangiocarci biliary stent noma with bilateral metal biliary stents

Abbreviations: SEMS- Self-Expandable Metal Stents; Modified BONA-AL - modified by enlarging the flares (22-mm external diameter) and the ends of the stent had 90°angulation to prevent migration after placement,

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S61- 5. 27. Kahaleh, M., et al., Drainage of gallbladder fossa fluid collections with endoprosthesis placement under endoscopic ultrasound guidance: a preliminary report of two cases. Endoscopy, 2005. 37(4): p. 393-6. 28. Talreja, J.P., et al., Transenteric drainage of pancreatic-fluid collections with fully covered self-expanding metallic stents (with video). Gastrointest Endosc, 2008. 68(6): p. 1199-203. FIGURE LEGENDS

1-Figure 1: EUS guided puncture of the gallbladder

2-Figure 2: Fluoroscopy images of balloon dilation

3-Figure 3: Endoscopic images of deployed lumen apposing metal stent between the gallbladder and the bulb