- Email: [email protected]
Antireflux stents
Techniques in Gastrointestinal Endoscopy (2010) 12, 216-224
Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com
Antireflux stents Hans-Ulrich Laasch, MRCP, FRCR,a Derrick F. Martin, FRCP, FRCRb aDepartment bAcademic
of Radiology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Department of GI-Radiology, South Manchester University Hospitals NHS Foundation Trust, Manchester M23
9LT, UK. KEYWORDS: Endoprosthesis; Esophageal stenosis; Esophageal neoplasms; Stents; Complications
Because of changing epidemiology, an increasing proportion of esophageal stents must be placed across the gastroesophageal junction (GEJ). However, stents allowing food to pass antegradely in the erect position equally facilitate regurgitation of gastric contents into the esophagus in the supine position. Reported rates of stent-induced reflux vary between 10% and 95%. To address this, a variety of stents have been developed incorporating an antireflux valve. Published evidence of their effectiveness is sparse and inconsistent. Results range from no effect to a nearly 20-fold reduction in patients requiring acid suppression after stenting. On average, valved stents seem at least as effective as additional proton pump inhibitor therapy, with the potential to prevent debilitating regurgitation and aspiration. Standalone valves for “retrofitting” are available for patients with severe reflux symptoms from an open stent. Stents placed across the GEJ have a 3 times higher risk of displacement, which is caused by the local anatomy and affects valved and open stents alike. This article reviews the history and current state of antireflux stents. © 2010 Elsevier Inc. All rights reserved.
In contrast to esophageal squamous cell carcinoma, adenocarcinoma of the gastroesophageal junction (GEJ) has a rapidly rising incidence,1,2 probably as a consequence of gastroesophageal reflux and Barrett’s metaplasia. A large proportion of patients are incurable at the time of diagnosis. Five-year survival is less than 10% and palliative stent insertion remains one of the main treatment strategies at the current time. The particular anatomy of the GEJ requires special considerations: 1. Because of the anterolateral course of the GEJ, increased stent flexibility is required for good alignment. 2. Stents placed across the cardia abolish the valve function of the lower esophageal sphincter: any food that passes antegradely through the stent may equally pass retrogradely through the stent when the patient lies
HUL was COOK Fellow in interventional radiology (2000-2004) and has acted as a technical consultant for Ella-CS. Address reprint requests to Hans-Ulrich Laasch, MRCP, FRCR, Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK. E-mail: [email protected] 1096-2883/10/$-see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2011.01.005
down because the GEJ becomes the “plug hole” of the stomach in the supine position. 3. Tumors of the cardia necessitate placement of the lower end of the stent within the stomach. This reduces fixation of the stent and results in increased migration, which is approximately 3 times higher than with stents placed entirely within the esophagus.3
Anatomy of the GEJ The esophagus passes through a posterior hiatus in the diaphragm and sweeps anterior and to the left to meet the gastric fundus. From a radiographic point of view it is important to understand that straight antero-posterior (AP) projections foreshorten the curve of the cardia and stricture length can be underestimated. The most accurate projection is a right anterior oblique or a left posterior oblique projection (Figure 1) and this should be taken into account during stenting procedures. The fundus, the upper part of the stomach under the left hemidiaphragm, derives its name from the fact that it “collects” gastric content in the supine position because it forms the lowest part of the stomach when lying on one’s back.
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Figure 3 Stent-induced reflux on sagittal reconstructions of a computed tomogram in the supine position. A (radiolucent) biodegradable Ella-BD stent is present across the gastroesophageal junction (arrowheads). Ingested contrast in the stomach (S) is seen to empty back into the esophagus (arrows).
Figure 1 Fluoroscopy of a lower esophageal adenocarcinoma. In the right posterior oblique projection (RPO) the cardia is straightened and obscured by the overlying dome of the gastric fundus (arrow). Left posterior oblique projection (LPO) shows the curve of the cardia and the exact insertion into the stomach (patient is in the prone position).
The gastric body ascends into the anterior abdomen and passes across the midline in front of the spine toward the pylorus. Consequently, any food or fluid within the stomach will pool over the GEJ in the supine position with hydrostatic pressure exerted onto it. To elicit gastroesophageal reflux during a barium meal, the patient is turned from a left lateral (right side up) to a supine and right lateral position
Figure 2 Gastroesophageal reflux during barium study. Changing position from supine (S) to right (R) precipitates frank reflux into the upper chest.
(left side up), during which fluid will readily pass through an incompetent lower esophageal sphincter into the chest (Figure 2). A stent holding the lower esophageal sphincter open will therefore allow gravity to drain the stomach into the esophagus as soon as the patient lies down (Figure 3). This is not an issue with stents placed above a functioning cardia; however, two-thirds of patients require stent placement across the GEJ. Stents placed with the lower end deep in the gastric body may theoretically induce less reflux, but the stomach is a mobile structure, which will peristalse around the stent and propel food into the lower opening. Choosing longer stents should also be resisted because the lower end may abut against the greater curve of the stomach, impairing outflow. To reduce the risk of regurgitation of gastric content, stents have been developed with simple one-way valves.
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Figure 4 Antireflux stents; see Table 1 for details. (A) Z-stent with Dua antireflux valve. (B) FerX-Ella stent. (C) BoubElla stent. (D) EllaHV stent; inset: antimigration collar. (E) Choo stent (Hanaro stent consisting of continuous woven nitinol skeleton); inset: discontinued Do “tricuspid” valve (top) and current wind sock valve (bottom). (F) Niti-S double stent; inset: uncovered antimigration sleeve. (G) Cardioumbrella stent; inset: internal flap valve closed and open. For technical details see Table 1. (Color version of figure is available online at www.techgiendoscopy.com).
These stents allow antegrade passage of food, but below a certain pressure prevent gastric content flushing back through the stent.
History The most common form of antireflux valve consists of a “wind sock” type tube attached to the lower end of the stent (Figure 4). This valve is designed to collapse with increased gastric pressure (Figure 5) and prevent reflux of gastric content into the esophagus. Valves do not completely prevent escape of gastric acid into the esophagus, and it is a common misconception that the occurrence of heartburn
Figure 5 Closed Dua valve seen on endoscopy. Reproduced with permission.4 (Color version of figure is available online at www.techgiendoscopy.com).
indicates failure of the valve. Indeed, most valves are designed to invert above a certain pressure to allow belching or vomiting (Figure 6). Hence, a degree of esophageal irritation by gastric acid is to be expected. The purpose of an antireflux valve is to prevent frank regurgitation of gastric content, which is a debilitating experience to many patients and has led to documented cases of aspiration pneumonia and death.4,5
Figure 6 Valve inversion from retching during endoscopy (FerX-Ella). Reproduced with permission.24 (Color version of figure is available online at www.techgiendoscopy.com).
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Figure 7 Esophageal perforation from pressure necrosis by an angulated Dua stent.
The first antireflux stents were produced by Ella-CS (Hradec Kralove, Czech Republic) and Cook Medical (Bloomington, IN). The initial designs had several disadvantages. The first-generation stainless-steel FerX-Ella was not very flexible and was plagued by a high migration rate. The Dua Z-stent consists of several stainless-steel segments connected by sutures and covered in polyurethane. The stent is rigid, resulting in poor alignment around the cardia, and
Figure 8 Compound delivery system (Ella HV and Ella BD): a long, flexible tip and a short dilatation segment (arrow), which splits into 2 small pieces to avoid impaction on removal. (Color version of figure is available online at www.techgiendoscopy.com).
Figure 9 (A) “Tricuspid” retrofit antireflux valve (Vysera, Galway, Ireland) seen from below (arrow indicates the tip of the delivery system). (B) Valve and its suspension system placed in a loading funnel (arrow) prior to withdrawal into the delivery system (arrowheads indicate loading string). (C) Insertion of valve delivery system. Frank reflux of contrast is seen through 2 coaxial stents [Niti-S double in lower esophagus; AlimaXX (Merit Medical, Coatbridge, UK) stent across the gastroesophageal junction]. The upper and lower markers of the valve system (arrows) are just seen within the refluxing contrast. (D) Deployed valve: The “V”-shape valve leaflets are outlined by refluxing contrast from below (arrow). (Color version of figure is available online at www.techgiendoscopy.com).
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Figure 10 (A) Inverted Ella-HV antireflux valve. Injection of contrast through a biliary manipulation catheter (William Cook, Bjaeverskov, Denmark; arrowhead) demonstrates the valve as a filling defect in the lower stent (arrow). (B) After forced injection of air through the catheter (arrowhead), the valve (arrow) extends through the gastroesophageal junction.
at times resulting in pressure necrosis of the lower esophagus (Figure 7). The stent itself has to be loaded prior to use by retraction into the delivery system using a string. The Czech company Ella-CS has produced a series of antireflux stents since 2000. The FerX-Ella stent was available on an innovative delivery system, which had an angioplasty balloon catheter at its center. When inflated, the
balloon acted as the tip of the delivery system and the stent was deployed after deflation. Because of its extremely low profile in a deflated state, the delivery system could always be removed without difficulty, even if the stent had not expanded well. The second generation (BoubElla) was constructed of separate segments of stainless-steel baskets covered in polyethylene foil. Migration rates were improved by
Figure 11 Symptomatic partial migration. (A) FerX-Ella stent has slipped until impacted in the greater curve of the stomach. (B) Successful extension with a Flamingo stent (Boston Scientific, St Albans, UK).
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Antireflux Stents
a larger inlet funnel and an antimigration “bulb” to be placed above the stricture. This design was superseded by a nitinol stent (Ella-HV), which has a forward-facing collar to anchor the stent above the tumor. In all 3 versions the antireflux valve consisted of a thin polyethylene tube. The current delivery system sheds part of its tip for easy removal after stent deployment (Figure 8). Over recent years Korea has established itself as one of the main drivers of stent technology because of a successful symbiosis of clinicians, academics, and industry. A different approach in valve construction was taken by M.I. Tech (Seoul, S. Korea). Similar to the appearance of the aortic valve in the human heart, a polyurethane valve made of 3 opposing leaflets was fashioned in the lower stent segment. The difficulty with this type of valve was the need for a concentric configuration of the segment containing the valve. Deformity of the lower stent by external compression would lead to gaping between the valve leaflets and poor valve function. The tricuspid valve of the original Do stent was replaced by a silicone wind sock mounted within the shaft of the stent itself. This stent is now available in 2 versions: the original Choo design consists of separate nitinol baskets connected by the polyethylene membrane, whereas the more recent Hanaro stent is made of a continuous nitinol skeleton. The former is more flexible, but the membrane connecting the individual segments may occasionally tear. Despite the valve being mounted within the shaft of the stent, there have been no reports of increased food impaction. Over the past few years disputes over patency issues among American, European, and Korean manufacturers had to be circumvented. TaeWoong (Seoul, S. Korea) initially produced an unvalved version of a “double” stent. This stent consisted of an uncovered segment of an enteral nitinol stent mounted on the outside of a dog bone–shape covered stent. This sleeve is supposed to allow the mucosa to grip the uncovered layer and reduce the amount of migration. Although migration rates are reduced compared with single dog bone–shape stents, the fixation is not as good as had been hoped for,6 probably because the outer segment can be readily compressed against the trunk of the stent. The stent was made available with a polytetrafluoroethylene (PTFE) valve with stabilizing side struts in 2009. The struts are designed to maintain a better configuration of the valve and prevent complete inversion as well as compression of the valve into the stent. An unusual version of a cardial stent is produced by Micro-Tech (Nanjing, China). The woven nitinol stent has an umbrella configuration that caps the gastric side of the cardia. Within the trunk of the stent is an oval silicone flap, which opens and closes the stent exit similar to a tilting-disk mechanical heart valve.
Performance in practice Although the concept of antireflux stents should intuitively appeal according to the laws of gravity, this is still
221 much debated. Initial experiments demonstrated the efficacy of valves in vitro and in animal experiments.7 Reported rates of reflux through open stents range widely and use different definitions, including reduced intraesophageal pH, heartburn, reflux requiring treatment, and frank regurgitation of food. Fatal aspiration from reflux through an open stent has been documented.4 Most papers demonstrate improvement in clinical symptoms8-11 and quality of life,12 as well as increased esophageal pH,13,14 with the use of valved stents. A smaller proportion of studies reported no difference,5,15 although Homs et al in the same paper reported a case of aspiration
Figure 12 (A) Complete migration: Niti-S double stent migrated under chemotherapy (patient unaware). The antimigration sleeve has detached from the stent and is seen separately in the gastric fundus (arrow). (B) Migrated BoubElla stent at the ileocecal junction. The patient was asymptomatic.
No Antimigration bulb (distal) Initially Uncovered outer sleeve Yes Dog bone
Flap Wind sock Wind sock
Yes Forward facing antimigration collar Abbreviations: S/S, stainless steel; NiTi, nitinol.
Yes Antimigration bulb (proximal) No Proximal uncovered segment Removable Shape/antimigration design
Yes Proximal flare
Wind sock Wind sock Wind sock Wind sock Valve
Manufacturer
Stent skeleton Cover material
S/S Polyethylene
S/S Polyethylene
NiTi Polyethylene
NiTi Polyethylene, PU valve Tricuspid valve Yes Dog bone
NiTi Polyethylene
NiTi Silicone, PTFE valve
Microtech (Nanjing, China) NiTi Silicone Taewoong Medical (Seoul, S. Korea) M.I. Tech (Seoul, S. Korea) Ella-CS (Hradec Kralove, Czech Republic)
Niti-S Double Ella-HV BoubElla FerX-Ella
Z-stent with Dua valve Cook Medical (Bloomington, IN) S/S Polyurethane Stent model
A
Do
Choo/Hanaro
F Table 1
Antireflux stent details
B
C
D
E
Figure 13 Endoscopic stent removal from a postradiation stricture. The green retrieval string (arrow) is captured with endoscopic forceps. Note early formation of a reactive stricture at the upper stent end (arrowheads) after only 2 weeks. (Color version of figure is available online at www.techgiendoscopy.com).
pneumonia in a patient with an open stent.5 One of the larger randomized series dismissed valved stents as no more effective than additional proton pump inhibitor therapy.16 However, the authors did not address the fact that these patients already suffer from dysphagia, and avoiding additional medication is a real bonus. Given the option, most patients would prefer to take fewer tablets. Symptoms from gastroesophageal reflux can be debilitating even without aspiration. Secondary placement of valved stents has been used successfully to reduce reflux caused by the use of open stents.17 Recently, a stand-alone antireflux valve has been developed that can be fitted into a deployed open stent. A tricuspid valve is suspended in a segment of uncovered enteral stent. After being loaded into a standard delivery system it is deployed coaxially within the esophageal stent (Figure 9). The valve is currently available in 18- and 23-mm diameters. Complications occurring from the use of valved stents are extremely rare. Occasional case reports of stent occlusion from inverted and impacted valves exist and we have observed 2 cases in 12 years where valve inversion after removal of the delivery system occluded the stent exit (Figure 10). This issue was readily dealt with either by pneumatic repositioning or by endoscopic perforation of the valve. The main risk of using antireflux stents is failure of the valve to prevent heartburn. In these cases there has been no additional detriment over the use of an open stent, although it is likely that the volume of regurgitated food is still reduced. The sparse evidence in the literature suggests that there is indeed a symptomatic reduction in reflux symptoms from the use of valved stents.
Cardioumbrella
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Migration It is a misconception by some operators that antireflux stents migrate more frequently. The design of the open and antireflux stents from the same manufacturer is identical; the only difference is the addition of a valve. By definition, however, valved stents are placed in the more hostile anatomy of the GEJ, where any stent—valved or not—is more likely to migrate than in the mid- and upper esophagus. Despite attempts at specific antimigration designs, migration rates across the cardia remain around 15% at best.3 Minor migration may still present a problem in a stomach with a horizontal alignment because the distal stent can embed in the greater curve, impairing outflow of food into the stomach (Figure 11). This situation is potentially worsened with a wind sock type valve. Stents that have slipped completely into the stomach usually remain asymptomatic. Of the few that pass into the small bowel, most are expelled per ano (Figure 12); however, cases of intestinal obstruction and fatal perforation have been reported.18-22 All current antireflux stents are equipped with a purse string at the proximal end, which allows relatively easy extraction with endoscopic forceps (Figure 13); this option should be considered in patients who are likely to survive longer. Biodegradable stents do not need removing, even when migrated23; however, valved versions are still being developed.
Cost Depending on the manufacturer and country of distribution, the premium for adding an antireflux valve to a stent varies between 0 and US$330. This cost must be offset against potential oral antireflux medication for a median survival of 3-4 months at a cost of $1–$2/day for even generic proton pump inhibitors. Once patients’ dysphagia and the occasional aspiration pneumonia are considered, there seems no discernible benefit in avoiding an antireflux valve. In summary, antireflux valves reduce the amount of gastroesophageal regurgitation in vitro and on contrast studies and computed tomography. Limited evidence also suggests variable amount of clinical benefit and the drawbacks from using valved stents are minimal. Valved stents are usually placed across the GEJ with a higher migration rate compared with stents placed above the cardia. The chances of stent failure increase with time and patients require continued easy access to specialist services.
References 1. Botterweck AA, Schouten LJ, Volovics A, et al: Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 29:645-654, 2000
223 2. Sihvo EI, Salminen JT, Ramo OJ, et al: The epidemiology of oesophageal adenocarcinoma: has the cancer of gastric cardia an influence on the rising incidence of oesophageal adenocarcinoma? Scand J Gastroenterol 35:1082-1086, 2000 3. British Society of Interventional Radiology. ROST—Registry of Oesophageal Stenting, First Report 2004. Henley-on-Thames: Dendrite Clinical Systems; 2004 4. Laasch HU, Marriott A, Wilbraham L, et al: Effectiveness of open versus antireflux stents for palliation of distal esophageal carcinoma and prevention of symptomatic gastroesophageal reflux. Radiology 225:359-365, 2002 5. Homs MY, Wahab PJ, Kuipers EJ, et al: Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc 60:695-702, 2004 6. British Society of Interventional Radiology: Registry of Oesophageal Stenting (ROST): 2009 Interim Report. Brighton, UK: British Society of Interventional Radiology; 2009 7. Dua KS, Kozarek R, Kim J, et al: Self-expanding metal esophageal stent with anti-reflux mechanism. Gastrointest Endosc 53:603-613, 2001 8. Kocher M, Dlouhy M, Neoral C, et al: Esophageal stent with antireflux valve for tumors involving the cardia: work in progress. J Vasc Interv Radiol 9:1007-1010, 1998 9. Do YS, Choo SW, Suh SW, et al: Malignant esophagogastric junction obstruction: palliative treatment with an antireflux valve stent. J Vasc Interv Radiol 12:647-651, 2001 10. Shim CS, Jung IS, Cheon YK, et al: Management of malignant stricture of the esophagogastric junction with a newly designed selfexpanding metal stent with an antireflux mechanism. Endoscopy 37: 335-339, 2005 11. Wenger U, Johnsson E, Arnelo U, et al: An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study. Surg Endosc 20:1675-1680, 2006 12. Power C, Byrne PJ, Lim K, et al: Superiority of anti-reflux stent compared with conventional stents in the palliative management of patients with cancer of the lower esophagus and esophago-gastric junction: results of a randomized clinical trial. Dis Esophagus 20:466470, 2007 13. Nunes CC, Waechter FL, Sampaio JA, et al: Comparative post-operative study of prostheses, with and without an anti-reflux valve system, in the palliative treatment of esophageal carcinoma. Hepatogastroenterology 46:2859-2864, 1999 14. Osugi H, Lee S, Higashino M, et al: Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction. Surg Endosc 16:14781482, 2002 15. Blomberg J, Wenger U, Lagergren J, et al: Anti-reflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol 45:208216, 2009 16. Sabharwal T, Gulati MS, Fotiadis N, et al: Randomised comparison of the FerX Ella anti-reflux stent and the Ultraflex stent: proton pump inhibitor combination for prevention of post-stent reflux in patients with esophageal carcinoma involving the esophago-gastric junction. J Gastroenterol Hepatol 23:723-728, 2008 17. Davies RP, Kew J, Byrne PD: Treatment of post-stent gastroesophageal reflux by anti-reflux Z-stent. Cardiovasc Interv Radiol 23:487489, 2000 18. Begbie S, Briggs G, Levi J: A late complication of palliative stenting of malignant oesophageal obstruction. Aust N Z J Med 26:115, 1996 19. Macdonald AJ, Drummond RJ, Wright DM: Migration of a metal esophageal stent presenting as obstruction at the ileocecal valve 2 years postinsertion. Endoscopy 39 (suppl 1):E190, 2007 20. De Palma GD, Iovino P, Catanzano C: Distally migrated esophageal self-expanding metal stents: wait and see or remove? Gastrointest Endosc 53:96-98, 2001
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21. Thuraisingam AI, Hughes ML, Smart HL: Down-staging of an advanced esophageal carcinoma with chemoradiotherapy leading to stent migration necessitating colectomy. Gastrointest Endosc 59:457-460, 2004 22. Furlong H, Nasr A, Walsh TN: Gastropleural fistula: a complication of esophageal self-expanding metallic stent migration. Endoscopy 41 (suppl 2):E38-E39, 2009
23. Stivaros SM, Williams LR, Senger C, et al: Woven polydioxanone biodegradable stents: a new treatment option for benign and malignant oesophageal strictures. Eur Radiol 20:1069-1072, 2010 24. Laasch HU, Martin DF, Do YS, et al: Interventional radiology for the management of inoperable carcinoma of the oesophagus. Endoscopy 35:1049-1057, 2003; discussion, 58
Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com
Antireflux stents Hans-Ulrich Laasch, MRCP, FRCR,a Derrick F. Martin, FRCP, FRCRb aDepartment bAcademic
of Radiology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Department of GI-Radiology, South Manchester University Hospitals NHS Foundation Trust, Manchester M23
9LT, UK. KEYWORDS: Endoprosthesis; Esophageal stenosis; Esophageal neoplasms; Stents; Complications
Because of changing epidemiology, an increasing proportion of esophageal stents must be placed across the gastroesophageal junction (GEJ). However, stents allowing food to pass antegradely in the erect position equally facilitate regurgitation of gastric contents into the esophagus in the supine position. Reported rates of stent-induced reflux vary between 10% and 95%. To address this, a variety of stents have been developed incorporating an antireflux valve. Published evidence of their effectiveness is sparse and inconsistent. Results range from no effect to a nearly 20-fold reduction in patients requiring acid suppression after stenting. On average, valved stents seem at least as effective as additional proton pump inhibitor therapy, with the potential to prevent debilitating regurgitation and aspiration. Standalone valves for “retrofitting” are available for patients with severe reflux symptoms from an open stent. Stents placed across the GEJ have a 3 times higher risk of displacement, which is caused by the local anatomy and affects valved and open stents alike. This article reviews the history and current state of antireflux stents. © 2010 Elsevier Inc. All rights reserved.
In contrast to esophageal squamous cell carcinoma, adenocarcinoma of the gastroesophageal junction (GEJ) has a rapidly rising incidence,1,2 probably as a consequence of gastroesophageal reflux and Barrett’s metaplasia. A large proportion of patients are incurable at the time of diagnosis. Five-year survival is less than 10% and palliative stent insertion remains one of the main treatment strategies at the current time. The particular anatomy of the GEJ requires special considerations: 1. Because of the anterolateral course of the GEJ, increased stent flexibility is required for good alignment. 2. Stents placed across the cardia abolish the valve function of the lower esophageal sphincter: any food that passes antegradely through the stent may equally pass retrogradely through the stent when the patient lies
HUL was COOK Fellow in interventional radiology (2000-2004) and has acted as a technical consultant for Ella-CS. Address reprint requests to Hans-Ulrich Laasch, MRCP, FRCR, Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK. E-mail: [email protected] 1096-2883/10/$-see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2011.01.005
down because the GEJ becomes the “plug hole” of the stomach in the supine position. 3. Tumors of the cardia necessitate placement of the lower end of the stent within the stomach. This reduces fixation of the stent and results in increased migration, which is approximately 3 times higher than with stents placed entirely within the esophagus.3
Anatomy of the GEJ The esophagus passes through a posterior hiatus in the diaphragm and sweeps anterior and to the left to meet the gastric fundus. From a radiographic point of view it is important to understand that straight antero-posterior (AP) projections foreshorten the curve of the cardia and stricture length can be underestimated. The most accurate projection is a right anterior oblique or a left posterior oblique projection (Figure 1) and this should be taken into account during stenting procedures. The fundus, the upper part of the stomach under the left hemidiaphragm, derives its name from the fact that it “collects” gastric content in the supine position because it forms the lowest part of the stomach when lying on one’s back.
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Figure 3 Stent-induced reflux on sagittal reconstructions of a computed tomogram in the supine position. A (radiolucent) biodegradable Ella-BD stent is present across the gastroesophageal junction (arrowheads). Ingested contrast in the stomach (S) is seen to empty back into the esophagus (arrows).
Figure 1 Fluoroscopy of a lower esophageal adenocarcinoma. In the right posterior oblique projection (RPO) the cardia is straightened and obscured by the overlying dome of the gastric fundus (arrow). Left posterior oblique projection (LPO) shows the curve of the cardia and the exact insertion into the stomach (patient is in the prone position).
The gastric body ascends into the anterior abdomen and passes across the midline in front of the spine toward the pylorus. Consequently, any food or fluid within the stomach will pool over the GEJ in the supine position with hydrostatic pressure exerted onto it. To elicit gastroesophageal reflux during a barium meal, the patient is turned from a left lateral (right side up) to a supine and right lateral position
Figure 2 Gastroesophageal reflux during barium study. Changing position from supine (S) to right (R) precipitates frank reflux into the upper chest.
(left side up), during which fluid will readily pass through an incompetent lower esophageal sphincter into the chest (Figure 2). A stent holding the lower esophageal sphincter open will therefore allow gravity to drain the stomach into the esophagus as soon as the patient lies down (Figure 3). This is not an issue with stents placed above a functioning cardia; however, two-thirds of patients require stent placement across the GEJ. Stents placed with the lower end deep in the gastric body may theoretically induce less reflux, but the stomach is a mobile structure, which will peristalse around the stent and propel food into the lower opening. Choosing longer stents should also be resisted because the lower end may abut against the greater curve of the stomach, impairing outflow. To reduce the risk of regurgitation of gastric content, stents have been developed with simple one-way valves.
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Figure 4 Antireflux stents; see Table 1 for details. (A) Z-stent with Dua antireflux valve. (B) FerX-Ella stent. (C) BoubElla stent. (D) EllaHV stent; inset: antimigration collar. (E) Choo stent (Hanaro stent consisting of continuous woven nitinol skeleton); inset: discontinued Do “tricuspid” valve (top) and current wind sock valve (bottom). (F) Niti-S double stent; inset: uncovered antimigration sleeve. (G) Cardioumbrella stent; inset: internal flap valve closed and open. For technical details see Table 1. (Color version of figure is available online at www.techgiendoscopy.com).
These stents allow antegrade passage of food, but below a certain pressure prevent gastric content flushing back through the stent.
History The most common form of antireflux valve consists of a “wind sock” type tube attached to the lower end of the stent (Figure 4). This valve is designed to collapse with increased gastric pressure (Figure 5) and prevent reflux of gastric content into the esophagus. Valves do not completely prevent escape of gastric acid into the esophagus, and it is a common misconception that the occurrence of heartburn
Figure 5 Closed Dua valve seen on endoscopy. Reproduced with permission.4 (Color version of figure is available online at www.techgiendoscopy.com).
indicates failure of the valve. Indeed, most valves are designed to invert above a certain pressure to allow belching or vomiting (Figure 6). Hence, a degree of esophageal irritation by gastric acid is to be expected. The purpose of an antireflux valve is to prevent frank regurgitation of gastric content, which is a debilitating experience to many patients and has led to documented cases of aspiration pneumonia and death.4,5
Figure 6 Valve inversion from retching during endoscopy (FerX-Ella). Reproduced with permission.24 (Color version of figure is available online at www.techgiendoscopy.com).
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Figure 7 Esophageal perforation from pressure necrosis by an angulated Dua stent.
The first antireflux stents were produced by Ella-CS (Hradec Kralove, Czech Republic) and Cook Medical (Bloomington, IN). The initial designs had several disadvantages. The first-generation stainless-steel FerX-Ella was not very flexible and was plagued by a high migration rate. The Dua Z-stent consists of several stainless-steel segments connected by sutures and covered in polyurethane. The stent is rigid, resulting in poor alignment around the cardia, and
Figure 8 Compound delivery system (Ella HV and Ella BD): a long, flexible tip and a short dilatation segment (arrow), which splits into 2 small pieces to avoid impaction on removal. (Color version of figure is available online at www.techgiendoscopy.com).
Figure 9 (A) “Tricuspid” retrofit antireflux valve (Vysera, Galway, Ireland) seen from below (arrow indicates the tip of the delivery system). (B) Valve and its suspension system placed in a loading funnel (arrow) prior to withdrawal into the delivery system (arrowheads indicate loading string). (C) Insertion of valve delivery system. Frank reflux of contrast is seen through 2 coaxial stents [Niti-S double in lower esophagus; AlimaXX (Merit Medical, Coatbridge, UK) stent across the gastroesophageal junction]. The upper and lower markers of the valve system (arrows) are just seen within the refluxing contrast. (D) Deployed valve: The “V”-shape valve leaflets are outlined by refluxing contrast from below (arrow). (Color version of figure is available online at www.techgiendoscopy.com).
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Figure 10 (A) Inverted Ella-HV antireflux valve. Injection of contrast through a biliary manipulation catheter (William Cook, Bjaeverskov, Denmark; arrowhead) demonstrates the valve as a filling defect in the lower stent (arrow). (B) After forced injection of air through the catheter (arrowhead), the valve (arrow) extends through the gastroesophageal junction.
at times resulting in pressure necrosis of the lower esophagus (Figure 7). The stent itself has to be loaded prior to use by retraction into the delivery system using a string. The Czech company Ella-CS has produced a series of antireflux stents since 2000. The FerX-Ella stent was available on an innovative delivery system, which had an angioplasty balloon catheter at its center. When inflated, the
balloon acted as the tip of the delivery system and the stent was deployed after deflation. Because of its extremely low profile in a deflated state, the delivery system could always be removed without difficulty, even if the stent had not expanded well. The second generation (BoubElla) was constructed of separate segments of stainless-steel baskets covered in polyethylene foil. Migration rates were improved by
Figure 11 Symptomatic partial migration. (A) FerX-Ella stent has slipped until impacted in the greater curve of the stomach. (B) Successful extension with a Flamingo stent (Boston Scientific, St Albans, UK).
Laasch and Martin
Antireflux Stents
a larger inlet funnel and an antimigration “bulb” to be placed above the stricture. This design was superseded by a nitinol stent (Ella-HV), which has a forward-facing collar to anchor the stent above the tumor. In all 3 versions the antireflux valve consisted of a thin polyethylene tube. The current delivery system sheds part of its tip for easy removal after stent deployment (Figure 8). Over recent years Korea has established itself as one of the main drivers of stent technology because of a successful symbiosis of clinicians, academics, and industry. A different approach in valve construction was taken by M.I. Tech (Seoul, S. Korea). Similar to the appearance of the aortic valve in the human heart, a polyurethane valve made of 3 opposing leaflets was fashioned in the lower stent segment. The difficulty with this type of valve was the need for a concentric configuration of the segment containing the valve. Deformity of the lower stent by external compression would lead to gaping between the valve leaflets and poor valve function. The tricuspid valve of the original Do stent was replaced by a silicone wind sock mounted within the shaft of the stent itself. This stent is now available in 2 versions: the original Choo design consists of separate nitinol baskets connected by the polyethylene membrane, whereas the more recent Hanaro stent is made of a continuous nitinol skeleton. The former is more flexible, but the membrane connecting the individual segments may occasionally tear. Despite the valve being mounted within the shaft of the stent, there have been no reports of increased food impaction. Over the past few years disputes over patency issues among American, European, and Korean manufacturers had to be circumvented. TaeWoong (Seoul, S. Korea) initially produced an unvalved version of a “double” stent. This stent consisted of an uncovered segment of an enteral nitinol stent mounted on the outside of a dog bone–shape covered stent. This sleeve is supposed to allow the mucosa to grip the uncovered layer and reduce the amount of migration. Although migration rates are reduced compared with single dog bone–shape stents, the fixation is not as good as had been hoped for,6 probably because the outer segment can be readily compressed against the trunk of the stent. The stent was made available with a polytetrafluoroethylene (PTFE) valve with stabilizing side struts in 2009. The struts are designed to maintain a better configuration of the valve and prevent complete inversion as well as compression of the valve into the stent. An unusual version of a cardial stent is produced by Micro-Tech (Nanjing, China). The woven nitinol stent has an umbrella configuration that caps the gastric side of the cardia. Within the trunk of the stent is an oval silicone flap, which opens and closes the stent exit similar to a tilting-disk mechanical heart valve.
Performance in practice Although the concept of antireflux stents should intuitively appeal according to the laws of gravity, this is still
221 much debated. Initial experiments demonstrated the efficacy of valves in vitro and in animal experiments.7 Reported rates of reflux through open stents range widely and use different definitions, including reduced intraesophageal pH, heartburn, reflux requiring treatment, and frank regurgitation of food. Fatal aspiration from reflux through an open stent has been documented.4 Most papers demonstrate improvement in clinical symptoms8-11 and quality of life,12 as well as increased esophageal pH,13,14 with the use of valved stents. A smaller proportion of studies reported no difference,5,15 although Homs et al in the same paper reported a case of aspiration
Figure 12 (A) Complete migration: Niti-S double stent migrated under chemotherapy (patient unaware). The antimigration sleeve has detached from the stent and is seen separately in the gastric fundus (arrow). (B) Migrated BoubElla stent at the ileocecal junction. The patient was asymptomatic.
No Antimigration bulb (distal) Initially Uncovered outer sleeve Yes Dog bone
Flap Wind sock Wind sock
Yes Forward facing antimigration collar Abbreviations: S/S, stainless steel; NiTi, nitinol.
Yes Antimigration bulb (proximal) No Proximal uncovered segment Removable Shape/antimigration design
Yes Proximal flare
Wind sock Wind sock Wind sock Wind sock Valve
Manufacturer
Stent skeleton Cover material
S/S Polyethylene
S/S Polyethylene
NiTi Polyethylene
NiTi Polyethylene, PU valve Tricuspid valve Yes Dog bone
NiTi Polyethylene
NiTi Silicone, PTFE valve
Microtech (Nanjing, China) NiTi Silicone Taewoong Medical (Seoul, S. Korea) M.I. Tech (Seoul, S. Korea) Ella-CS (Hradec Kralove, Czech Republic)
Niti-S Double Ella-HV BoubElla FerX-Ella
Z-stent with Dua valve Cook Medical (Bloomington, IN) S/S Polyurethane Stent model
A
Do
Choo/Hanaro
F Table 1
Antireflux stent details
B
C
D
E
Figure 13 Endoscopic stent removal from a postradiation stricture. The green retrieval string (arrow) is captured with endoscopic forceps. Note early formation of a reactive stricture at the upper stent end (arrowheads) after only 2 weeks. (Color version of figure is available online at www.techgiendoscopy.com).
pneumonia in a patient with an open stent.5 One of the larger randomized series dismissed valved stents as no more effective than additional proton pump inhibitor therapy.16 However, the authors did not address the fact that these patients already suffer from dysphagia, and avoiding additional medication is a real bonus. Given the option, most patients would prefer to take fewer tablets. Symptoms from gastroesophageal reflux can be debilitating even without aspiration. Secondary placement of valved stents has been used successfully to reduce reflux caused by the use of open stents.17 Recently, a stand-alone antireflux valve has been developed that can be fitted into a deployed open stent. A tricuspid valve is suspended in a segment of uncovered enteral stent. After being loaded into a standard delivery system it is deployed coaxially within the esophageal stent (Figure 9). The valve is currently available in 18- and 23-mm diameters. Complications occurring from the use of valved stents are extremely rare. Occasional case reports of stent occlusion from inverted and impacted valves exist and we have observed 2 cases in 12 years where valve inversion after removal of the delivery system occluded the stent exit (Figure 10). This issue was readily dealt with either by pneumatic repositioning or by endoscopic perforation of the valve. The main risk of using antireflux stents is failure of the valve to prevent heartburn. In these cases there has been no additional detriment over the use of an open stent, although it is likely that the volume of regurgitated food is still reduced. The sparse evidence in the literature suggests that there is indeed a symptomatic reduction in reflux symptoms from the use of valved stents.
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Migration It is a misconception by some operators that antireflux stents migrate more frequently. The design of the open and antireflux stents from the same manufacturer is identical; the only difference is the addition of a valve. By definition, however, valved stents are placed in the more hostile anatomy of the GEJ, where any stent—valved or not—is more likely to migrate than in the mid- and upper esophagus. Despite attempts at specific antimigration designs, migration rates across the cardia remain around 15% at best.3 Minor migration may still present a problem in a stomach with a horizontal alignment because the distal stent can embed in the greater curve, impairing outflow of food into the stomach (Figure 11). This situation is potentially worsened with a wind sock type valve. Stents that have slipped completely into the stomach usually remain asymptomatic. Of the few that pass into the small bowel, most are expelled per ano (Figure 12); however, cases of intestinal obstruction and fatal perforation have been reported.18-22 All current antireflux stents are equipped with a purse string at the proximal end, which allows relatively easy extraction with endoscopic forceps (Figure 13); this option should be considered in patients who are likely to survive longer. Biodegradable stents do not need removing, even when migrated23; however, valved versions are still being developed.
Cost Depending on the manufacturer and country of distribution, the premium for adding an antireflux valve to a stent varies between 0 and US$330. This cost must be offset against potential oral antireflux medication for a median survival of 3-4 months at a cost of $1–$2/day for even generic proton pump inhibitors. Once patients’ dysphagia and the occasional aspiration pneumonia are considered, there seems no discernible benefit in avoiding an antireflux valve. In summary, antireflux valves reduce the amount of gastroesophageal regurgitation in vitro and on contrast studies and computed tomography. Limited evidence also suggests variable amount of clinical benefit and the drawbacks from using valved stents are minimal. Valved stents are usually placed across the GEJ with a higher migration rate compared with stents placed above the cardia. The chances of stent failure increase with time and patients require continued easy access to specialist services.
References 1. Botterweck AA, Schouten LJ, Volovics A, et al: Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol 29:645-654, 2000
223 2. Sihvo EI, Salminen JT, Ramo OJ, et al: The epidemiology of oesophageal adenocarcinoma: has the cancer of gastric cardia an influence on the rising incidence of oesophageal adenocarcinoma? Scand J Gastroenterol 35:1082-1086, 2000 3. British Society of Interventional Radiology. ROST—Registry of Oesophageal Stenting, First Report 2004. Henley-on-Thames: Dendrite Clinical Systems; 2004 4. Laasch HU, Marriott A, Wilbraham L, et al: Effectiveness of open versus antireflux stents for palliation of distal esophageal carcinoma and prevention of symptomatic gastroesophageal reflux. Radiology 225:359-365, 2002 5. Homs MY, Wahab PJ, Kuipers EJ, et al: Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc 60:695-702, 2004 6. British Society of Interventional Radiology: Registry of Oesophageal Stenting (ROST): 2009 Interim Report. Brighton, UK: British Society of Interventional Radiology; 2009 7. Dua KS, Kozarek R, Kim J, et al: Self-expanding metal esophageal stent with anti-reflux mechanism. Gastrointest Endosc 53:603-613, 2001 8. Kocher M, Dlouhy M, Neoral C, et al: Esophageal stent with antireflux valve for tumors involving the cardia: work in progress. J Vasc Interv Radiol 9:1007-1010, 1998 9. Do YS, Choo SW, Suh SW, et al: Malignant esophagogastric junction obstruction: palliative treatment with an antireflux valve stent. J Vasc Interv Radiol 12:647-651, 2001 10. Shim CS, Jung IS, Cheon YK, et al: Management of malignant stricture of the esophagogastric junction with a newly designed selfexpanding metal stent with an antireflux mechanism. Endoscopy 37: 335-339, 2005 11. Wenger U, Johnsson E, Arnelo U, et al: An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study. Surg Endosc 20:1675-1680, 2006 12. Power C, Byrne PJ, Lim K, et al: Superiority of anti-reflux stent compared with conventional stents in the palliative management of patients with cancer of the lower esophagus and esophago-gastric junction: results of a randomized clinical trial. Dis Esophagus 20:466470, 2007 13. Nunes CC, Waechter FL, Sampaio JA, et al: Comparative post-operative study of prostheses, with and without an anti-reflux valve system, in the palliative treatment of esophageal carcinoma. Hepatogastroenterology 46:2859-2864, 1999 14. Osugi H, Lee S, Higashino M, et al: Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction. Surg Endosc 16:14781482, 2002 15. Blomberg J, Wenger U, Lagergren J, et al: Anti-reflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol 45:208216, 2009 16. Sabharwal T, Gulati MS, Fotiadis N, et al: Randomised comparison of the FerX Ella anti-reflux stent and the Ultraflex stent: proton pump inhibitor combination for prevention of post-stent reflux in patients with esophageal carcinoma involving the esophago-gastric junction. J Gastroenterol Hepatol 23:723-728, 2008 17. Davies RP, Kew J, Byrne PD: Treatment of post-stent gastroesophageal reflux by anti-reflux Z-stent. Cardiovasc Interv Radiol 23:487489, 2000 18. Begbie S, Briggs G, Levi J: A late complication of palliative stenting of malignant oesophageal obstruction. Aust N Z J Med 26:115, 1996 19. Macdonald AJ, Drummond RJ, Wright DM: Migration of a metal esophageal stent presenting as obstruction at the ileocecal valve 2 years postinsertion. Endoscopy 39 (suppl 1):E190, 2007 20. De Palma GD, Iovino P, Catanzano C: Distally migrated esophageal self-expanding metal stents: wait and see or remove? Gastrointest Endosc 53:96-98, 2001
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21. Thuraisingam AI, Hughes ML, Smart HL: Down-staging of an advanced esophageal carcinoma with chemoradiotherapy leading to stent migration necessitating colectomy. Gastrointest Endosc 59:457-460, 2004 22. Furlong H, Nasr A, Walsh TN: Gastropleural fistula: a complication of esophageal self-expanding metallic stent migration. Endoscopy 41 (suppl 2):E38-E39, 2009
23. Stivaros SM, Williams LR, Senger C, et al: Woven polydioxanone biodegradable stents: a new treatment option for benign and malignant oesophageal strictures. Eur Radiol 20:1069-1072, 2010 24. Laasch HU, Martin DF, Do YS, et al: Interventional radiology for the management of inoperable carcinoma of the oesophagus. Endoscopy 35:1049-1057, 2003; discussion, 58