Esophageal cancer is diagnosed in about 400,000 patients each year worldwide, and its incidence is increasing faster than that of any other malignancy. This makes it the ninth most common malignancy and sixth on the list of cancer mortality causes. Most patients with esophageal cancer present at a stage that is too advanced for curative therapy, and many die within a few months. Treatment of dysphagia is the main goal of palliative care in more than 50% of incurable cases. Although many different palliative options for malignant dysphagia are available, expandable stent placement is the most commonly performed treatment modality.
Esophageal cancer ( Fig. 1 ) is diagnosed in about 400,000 patients each year worldwide, and its incidence, particularly that of adenocarcinoma in the Western world, is increasing faster than that of any other malignancy. This increasing incidence makes it the ninth most common malignancy and sixth on the list of cancer mortality causes. Notwithstanding recent progress in surgical and oncological treatment, most patients with esophageal cancer (50%–60%) present at a stage that is too advanced for curative therapy, with many patients dying within a few months. Treatment of dysphagia is the main goal of palliative care in more than 50% of these incurable cases. Although many different palliative options for malignant dysphagia, such as radiotherapy, laser, argon plasma coagulation, photodynamic therapy, local injection of alcohol, or chemotherapeutic agents, are available, expandable stent placement is the most commonly performed treatment modality worldwide because the above-mentioned options are less efficacious, more frequently associated with complications, or logistically more challenging.
Esophageal cancer
Rapid and persistent palliation of dysphagia is one of the main challenges in treating patients with incurable esophageal cancer to improve their quality of life. Brachytherapy and placement of an expandable stent are the 2 most evidence-based palliative treatment options for these patients. Two randomized controlled studies comparing expandable stent placement with brachytherapy have shown that self-expandable metal stent (SEMS) insertion provides rapid palliation of dysphagia when compared with brachytherapy. This difference in efficacy diminishes gradually over time, and brachytherapy seems to provide better relief of dysphagia after 3 months of follow-up. However, in the study by Homs and colleagues, the positive long-term outcome of brachytherapy was found in an intention-to-treat analysis, taking into account that 45 of the 101 patients allocated to brachytherapy also received a SEMS during follow-up for recurrent ( Fig. 2 ) or persistent dysphagia, whereas only 2 of the 108 patients allocated to SEMS placement received additional brachytherapy. The long-term more-beneficial effect of brachytherapy may therefore be explained partly by additional SEMS placement during follow-up because of a lack of brachytherapy effect.
A broad array of expandable stent types is available to palliate malignant dysphagia ( Fig. 3 ). The availability of so many different expandable stent designs attests to the fact that not one of the stents used today is significantly superior in all aspects to the others. However, one stent design does not fit all patients, and each stent type has specific features, which are advantageous or disadvantageous for stenting esophageal cancer ( Table 1 ).
| Stent Type | Advantage | Disadvantage |
|---|---|---|
| Partially covered SEMS | Low migration risk | Tissue ingrowth or overgrowth at stent ends Removal may be difficult |
| Fully covered SEMS | Safe and easy removal Low risk of tissue ingrowth | High migration risk Tissue hyperplasia at stent ends |
| SEPS | Safe and easy removal Low rate of hyperplastic overgrowth at stent ends No tissue ingrowth | High migration risk Complex and stiff/large introducer system |
At present, 2 main categories of expandable stents are being used, such as SEMSs, which can be partially or fully covered, and self-expandable plastic stents (SEPSs). The most commonly used modern SEMSs in the Western world, such as the Ultraflex (Boston Scientific, Natick, MA, USA), Wallflex (Boston Scientific), Evolution (Cook Ireland Ltd, Limerick, Ireland), and Niti-S (Taewoong-Medical Co Ltd, Seoul, Korea) stents, are made of single or multiple braided nitinol wires with a silicone or polyurethane covering. The only commercially available SEPS (Polyflex stent, Boston Scientific) is built of a monofilament polyester infrastructure with a complete silicone cover. Rapid palliation of dysphagia, resulting in a decrease of the dysphagia score from 3 (able to swallow liquids) to 1 (occasional dysphagia for some solid food), is observed after placement of all the above-mentioned expandable stent types.
One of the main drawbacks in the palliation of malignant dysphagia with expandable stents is the occurrence of recurrent dysphagia because of stent migration, tumoral and nontumoral tissue ingrowth or overgrowth, or food impaction. Prevention of these stent-related complications remains one of the major challenges for developing new stent designs.
Recurrent Dysphagia
Stent migration
Several stent- and patient-related factors are known risk factors for stent migration, leading to recurrent dysphagia. Migration is more frequently observed when a stent is placed across the gastroesophageal (GE) junction, probably because the distal stent end projects freely in the gastric lumen and is therefore not fixed to the gastric wall. Regression of tumor volume because of concurrent chemotherapy and radiotherapy is another cause of stent migration.
In general, migration rates of fully covered stents, either SEMSs or SEPSs, are higher than those of partially covered stents. Embedding of the uncovered stent ends leads to better fixation of the stent to the esophageal wall. The advantage of fully covered stents is that it allows removal if indicated, although this is rarely needed in incurable esophageal cancer. Studies on partially covered stents, such as the Ultraflex, Evolution, and Wallflex stents, have shown migration rates of 4% to 23%, 5%, and 6%, respectively, whereas the fully covered Alimaxx-E stent (Alveolus, Charlotte, NC, USA) has been reported to migrate in 36% of cases. This rather high migration rate was found despite the fact that 20 antimigration struts were attached to the outside of the stent.
In the previous 5 years, many other antimigration modifications to the design of esophageal fully covered expandable stents have been developed ( Table 2 ). The SX-Ella stent (Ella-CS, Hradec Kralove, Czech Republic) has an antimigration ring circumferentially attached to the proximal portion of the stent. This ring not only functions as a circular hook preventing migration but also has a mechanism that reduces risk of injury to the esophageal wall with excessive traction. The stent flares to 25 mm at its proximal and distal ends and has a midbody diameter of 20 mm. Uitdehaag and colleagues treated 44 patients with the SX-Ella stent and found improvement in the dysphagia score form 3 to 1. However, stent migration leading to recurrent dysphagia was observed in 14% to 20% of patients, suggesting that the antimigration ring and flares are not sufficient in preventing migration. Moreover, hemorrhage (25%) and fistula formation (6%) were frequently observed with this stent type. The investigators hypothesized that these complications might have been caused by friction of the antimigration ring resulting in esophageal wall injury.
| Stent Modification | Efficacy | Drawback |
|---|---|---|
| Small struts on the outside | − | None |
| Antimigration collar | +/− | Hemorrhage/fistula |
| Outer uncovered mesh | +/− | Inability to remove |
| Large-diameter stent/flares | + | Hemorrhage/perforation/fistula |
The fully covered Niti-S antimigration stent (Taewoong Medical Co Ltd) has a double-layer configuration over its entire length, consisting of an inner polyurethane layer and an outer uncovered nitinol mesh, which allows stent embedding to prevent migration. Relatively large flares of 26 mm at both ends are a second antimigration feature of this stent design. Verschuur and colleagues performed a randomized trial (n = 125 patients) comparing the Niti-S stent with the Ultraflex and Polyflex stents. Although these 3 stent designs were equally effective and safe for palliation of malignant dysphagia, stent migration was most frequently seen with the Polyflex stent (29%). The Ultraflex and double-layer Niti-S stents had similar stent migration rates of 17% and 12%, respectively.
Large-diameter expandable stents were introduced to reduce the risk of migration, which is because of an increased expansile pressure on the esophageal wall. An analysis of a large database of 338 patients treated with 3 types of stents (Ultraflex, Flamingo Wallstent [Boston Scientific], or Gianturco Z-stent [Cook Ireland Ltd]) with small or large diameters showed that large-diameter stents reduce the risk of recurrent dysphagia from stent migration, tissue overgrowth, or food obstruction (adjusted hazard ratio, 0.35; 95% confidence interval [CI], 0.2–0.7). The downside of placement of a wide-body stent, however, was the increased risk of stent-related complications, such as hemorrhage, perforation, fistula, and fever, which was particularly true for the wide-body Gianturco Z-stent (adjusted hazard ratio, 5.0; 95% CI, 1.3–19.1).
If the stent migrates to the stomach or bowel, the authors advise stent removal, preferably endoscopically, to prevent further injury to the gastrointestinal tract. Complications caused by migrated expandable esophageal stents, such as small bowel obstruction or perforation and formation of a gastropleural fistula, have been reported. The authors’ own (F.P.V. and P.D.S., unpublished data, 2011) experience is similar to these findings.
Tumoral or nontumoral tissue ingrowth or overgrowth
Stent occlusion because of ingrowth of tissue through the uncovered mesh or overgrowth at the stent ends is another cause of recurrent dysphagia. The incidence of tissue ingrowth and overgrowth at uncovered stent ends varies from 3% to 31% in series using the Ultraflex stent, whereas it was reported in 14% and 10% of cases after placement of the partially covered Evolution and Wallflex stents, respectively. The risk of developing stent occlusion because of reactive tissue growth increases with longer dwell times. Radial force and diameter of the stent as well as the nitinol or metal material of the stent seem to be the other factors causing reactive tissue ingrowth and overgrowth.
Tissue ingrowth and, to some extent, overgrowth is thought to be reduced with fully covered stents, although overgrowth has been reported in 10% to 30% of cases with a fully covered Alimaxx-E stent and in 5% to 24% of cases treated with a Niti-S stent. The risk of developing tumoral overgrowth can be reduced by using stents that are substantially longer than the malignant stricture.
Fully covered SEPSs, with the Polyflex being the only stent that is commercially available, induce less-reactive nontumoral tissue growth. Verschuur and colleagues showed that tissue ingrowth or overgrowth occurred more frequently with partially covered Ultraflex stents (31%) than with Polyflex stents (10%) or fully covered Niti-S stents (24%). This cause of recurrent dysphagia was observed after a median of 79 days after stent placement and treated by placement of a second stent. However, a randomized study by Conio and colleagues that compared the Ultraflex stent with the Polyflex stent did not show a difference in hyperplastic tissue reaction.
The Polyflex stent has some features that might increase the risk of esophageal perforation. The applicator, in which the stent is loaded before placement, has a diameter of 12 to 14 mm depending on stent size, and is rather rigid. In addition, the dilator at the tip of the introducer system is short, which may complicate its passage across angulated strictures because of inappropriate transmission of force. Another drawback of the Polyflex stent is its known relatively high migration rate, particularly in cases with distal stenoses. This is a significant problem. Migration rates range from 13% to 29% in randomized studies comparing SEPSs with SEMSs in patients with unresectable esophageal cancer.
Food obstruction
Food impaction within the stent is yet another cause of recurrent dysphagia. The incidence of this complication varies, but with the latest versions of stents, such as the Evolution and Wallflex, symptomatic food impaction was observed in just 7% and 5% of patients, respectively. This low frequency may be because of the smooth silicone covering on the inside of these stents, which facilitates food passage through the stent. To reduce the risk of this complication, patients should be advised to chew thoroughly and to drink, preferably carbonated beverages, during and after a meal.
Pain
The rate of retrosternal pain after stent placement seems to vary depending on the type of stent used. A relatively high frequency of retrosternal pain was observed after placement of partially covered Wallflex (31%) and Alimaxx-E stents (22%). In contrast, pain was less frequently observed after placement of an Evolution stent (9%), Ultraflex stent (6%–7%), Choostent (MI Tech Co Ltd, Seoul, Korea, 3%), and Niti-S stent (10%–12%). Increased expansion force and decreased flexibility of some stent types may play a role in inducing retrosternal pain. Because it has been demonstrated that previous radiation and/or chemotherapy is associated with a higher risk of retrosternal pain after stent placement, the above-mentioned pain rates may be because of potential bias. The authors advise prescribing opiates when there is retrosternal pain after expandable stent placement.
GE reflux
Stent placement across the GE junction may lead to reflux of gastric contents in some patients because a stent in this position prevents the lower esophageal sphincter to function. These patients are best treated with high-dose proton pump inhibitors (PPIs); however, in some patients, reflux symptoms persist despite treatment with PPIs. These patients may be candidates for an antireflux stent.
Several antireflux stent designs have been evaluated in randomized trials. Placement of a Z-stent (Cook Medical Inc, Limerick, Ireland) with a windsocklike valve on the distal end to prevent GE reflux was found to significantly reduce reflux symptoms compared with the standard open stents, but more objective data, such as pH measurement, were not obtained. The Fer-X Ella stent (Ella-CS) actually resulted in increased reflux symptoms and total acid exposure time in the antireflux stent group compared with the open stent group. Inadequate valve characteristics, such as a relatively short length of the windsock valve and the floppy material used, were thought to be the underlying causes of this surprising outcome. To further evaluate antireflux stents, a Korean study group compared the Do stent (MI Tech Co Ltd) that has a tricuspid antireflux valve, another antireflux stent with an S-shaped valve and long leaflets (MI Tech Co Ltd), and a standard open stent (MI Tech). The S-shaped valve significantly reduced reflux symptoms and total acid exposure time compared with the open and Do stents.
Given the conflicting results in different studies with different stent designs, the authors do not recommend the routine use of antireflux stents in patients with distal esophageal or gastric cardia cancer.
Related posts:
Pancreaticobiliary and Gastrointestinal Stents
Expandable Metal Stents: Principles and Tissue Responses
Expandable Stents for Benign Esophageal Disease
Expandable Metal Stents for Benign Biliary Disease
Self-Expandable Metal Stents for Malignant Distal Biliary Strictures
Expandable Metal Stents for Malignant Hilar Biliary Obstruction
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