Historically, stenting to relieve malignant strictures of the esophagus involved the use of plastic stents. Typically, these stents had a 10-mm internal diameter with proximal and distal flanges and were placed using an open traction or pulsion technique. With the traction technique, the patient underwent a laparotomy and a gastrotomy. A bougie was advanced orally and retrieved through the gastrotomy. The stent was attached to the bougie and pulled into place. With the pulsion technique, which could be performed under sedation, a guidewire was placed, the obstructing stricture was dilated, and the stent was advanced into position using an introducer device. Complications associated with plastic stents included stent displacement, food impaction, and intractable reflux for stents positioned across the gastroesophageal junction. In one report of 409 patients, this approach improved symptoms of dysphagia in 80% of patients but was associated with a 3% mortality rate.1 In another report comparing traction and pulsion techniques, mortality and length of stay were lower for patients treated using the pulsion technique (14% and 8.4 days, respectively) than those treated using the traction technique (23% and 18.6 days, respectively).2
Fortunately, the advent of self-expanding metal stents (SEMSs) has simplified palliation. The SEMS can be placed under endoscopic and fluoroscopic guidance. This approach does not require general anesthesia (though this may be preferable) or aggressive dilation of the malignant stricture. The stent itself is embedded within the tumor. Consequently, the likelihood of migration is small. The benefits of SEMSs over the earlier plastic stents have been demonstrated in a clinical trial, which showed similar improvement in dysphagia scores using both the techniques, but absence of early complications among patients treated with metal stents as compared to 20% early morbidity and 16% mortality among patients treated with plastic stents.3
In general, over 85% of patients are palliated immediately from their dysphagia symptoms when an SEMS approach is used. In cases where stenting is not able to relieve dysphagia, technical issues, such as poor stent expansion or malposition, are generally to blame and may be remedied by removing the stent and replacing it with a more appropriately sized device. In addition, an alternate treatment—such as cryoablation or PDT—may be used concurrently.
The newer generation SEMSs are constructed from various materials that include cobalt alloys (Wallstent, Schneider, Minneapolis, MN), stainless steel (Z-stent, Cook, Bloomington, IN), and a nickel—titanium alloy called nitinol (Esophacoil, Medtronic, Minneapolis, MN; Ultraflex, Boston Scientific, Natick, MA). These materials are resistant to corrosion and biologically inert.
The wire stents may be woven (Wallstent), knitted (Ultraflex), or bent into a zigzag (Z-stent) or coil (Esophacoil) configuration. Some stents also have windsock-type valves that serve as antireflux mechanisms (Dua Z-stent, Cook; FerX-ELLA, ELLA-CS, Czech Republic). The stent design influences its retraction properties. Retraction percentage is higher with the coil than with the zigzag configuration. The shape—memory characteristics of these metals and alloys permit the stent to reexpand to its original tubular shape even after it has been compressed into a delivery system.
The SEMS systems vary in deployment mechanisms. Some may be deployed with the removal of a suture (Ultraflex) whereas others are released using a sheath and pusher-rod mechanism. Also, the available systems include stents that can be deployed from the proximal end, the center, or the distal end. Proximal deployment (where the stent expands from a proximal-to-distal direction) is better suited for proximal strictures close to the cricopharyngeus muscle, whereas distal deployment (where the stent expands from a distal-to-proximal direction) is more suitable for obstructions located close to the gastroesophageal junction.
The SEMS is also available as a covered or uncovered device. Covered designs help to reduce tumor ingrowth but also increase the risk of migration. Because most stents are uncovered at the proximal and distal ends, the tendency for migration may be limited albeit at the expense of potential tumor ingrowth. In cases of excessive ingrowth, the tumor may be ablated using cryotherapy, PDT, or laser therapy, and additional stents may be deployed. If laser ablation is considered for treating tumor ingrowth, it should only be used with uncovered stents because of the risk of fire with covered stents. Covered stents also have properties especially suited for the management of tracheoesophageal fistulas,4 and can play a role in the management of anastomotic leaks and perforations.5 Examples of covered SEMS include the Ultraflex stent and the Alveolus stent (Merit Medical Endotek, South Jordan, UT). The wide range of available diameters and lengths permits the use of the SEMS for most esophageal lesions.
A recent innovation in stent technology is the self-expanding plastic stent (Polyflex Esophageal Stent, Boston Scientific, Natick, MA). As with the SEMS, these stents can be placed without the need for aggressive predilation. However, the self-expanding plastic stent also can be removed because there is no tissue ingrowth, and, for this reason, it is preferred for benign strictures. The self-expanding plastic stents have a high migration rate reported from 25–46%.6–8
PDT is a nonthermal, light-activated ablative treatment option. In this approach, a patient is given an intravenous administration of a photosensitive substance that accumulates in the esophageal tumor. This photosensitizing agent, when activated by a light source of a specific wavelength, causes selective tissue destruction with the goal of restoring esophageal patency. Currently, Photofrin (porfimer sodium; Pinnacle Biologics, Inc, Bannockburn, IL) is the only photosensitizer approved by the Food and Drug Administration for esophageal cancer and high-grade dysplasia of the esophagus, and its optimal wavelength of light absorption is 630 nm.
Photosensitizing agents accumulate in all cells of the body. However, after 1 to 4 days following administration, higher concentrations are found within the substance of the tumor. This phenomenon is thought to be either due to altered lymphatic drainage, neovascularization associated with the tumor, or increased cellular proliferation. Light of a specific wavelength that is delivered to the esophageal tumor—with a concentrated amount of the photosensitizer—triggers a series of processes that catalyze the formation of oxygen radical species that promote cell destruction. The targets of the oxygen radical species are cellular components—phospholipid membranes, amino acids, nucleosides, etc. Typically, the depth of penetration and tumor necrosis with this approach is 5 mm. Because of this limited degree of ablation, the risk of perforation is lower with PDT than when a thermal laser is used. However, PDT may be inadequate in the presence of large and bulky tumors, or if there is significant extrinsic compression, for instance, from nodal disease outside the lumen of the esophagus.
Cryoablation using endoscopic spray cryotherapy (CryoSpray Ablation System; CSA Medical, Baltimore, MD) is a relatively newer treatment modality. In this approach, low-pressure liquid nitrogen is sprayed onto the esophageal tumor under endoscopic visualization. Clinical use of this technology was first reported by Johnston et al.9 in treating Barrett's metaplasia in 2005. A follow-up case report by the same group10—describing the efficacy of this approach in treating a medically inoperable 73-year-old man with malignant dysphagia—demonstrated the potential utility of spray cryotherapy in the palliation of esophageal cancer.
Spray cryotherapy with low-pressure liquid nitrogen is designed to deliver a high rate of thermal energy transfer through a 7-Fr catheter—placed through the working channel of an endoscope—without making direct contact to the esophageal mucosa or tumor. This approach delivers approximately 25 W of energy to the targeted area, and is similar to the energy transfer of a laser and even several factors greater than the energy transfer of cryotherapy using a standard cryotherapy probe. The use of liquid nitrogen in rapidly delivering thermal energy at -196°C effectively flash-freezes the tissue and results in immediate cell death. Spray cryotherapy maintains the underlying tissue architecture and fosters a favorable wound healing response with minimal scarring. We have successfully used spray cryotherapy to treat bleeding related to esophageal tumors, as well as areas of tumor ingrowth/overgrowth around stents. We find it less useful for palliation of dysphagia in patients with obstructing tumors, since it is necessary to place a decompression tube into the stomach alongside the gastroscope. This tube is necessary to prevent overexpansion of the stomach as the liquid nitrogen vaporizes into gas with warming.
Laser ablation for malignant esophageal strictures initially involved the use of either an argon or neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Over time, the Nd:YAG laser gained in popularity due to its efficacy, although it is also associated with a perforation rate of 7% to 10%. It is an especially useful treatment option in the patient with advanced esophageal cancer with bleeding from the tumor. Treatment with Nd:YAG laser therapy usually involves the delivery of up to 90 W of energy in pulses of up to 1 second, at a wavelength of 1064 nm. While it is more useful for tumors of the airway, which tend to be only a few centimeters in length, we use it occasionally to treat small endoluminal tumors of the esophagus in patients with tumor overgrowth close to an uncovered stent or at the site of a previous esophagogastrostomy.
Generally, under fluoroscopic guidance, a guidewire is advanced beyond the malignant stricture, which is widened with a Savary dilator. Thereafter, a laser probe is advanced through an endoscope which is brought into approximation with the tumor. The luminal surface of the obstructing or bleeding tumor is treated with the laser in a point-by-point fashion. This process has the potential to be time-consuming for larger tumors. Also, because this approach may be of limited benefit within patients with bulky tumors causing extraluminal compression, and on account of the increased rate of perforation associated with both the laser treatment and the simultaneous dilation procedure that is often needed, patients are often better palliated with stents, PDT, or cryoablation.
Chemoradiation therapy can also be used to palliate patients with dysphagia from esophageal cancer, although the effects of this approach are not immediate and in many cases there is initial worsening of symptoms before improvement is achieved. In a report by Harvey et al.11, 106 patients with malignant dysphagia from esophageal cancer were evaluated and treated by chemoradiation therapy for palliative intent. Dysphagia was measured using a modified DeMeester (4-point) scoring system. In this series, 78% of the 102 patients available for posttreatment dysphagia scoring had an improvement of at least one grade in their dysphagia, 49% of patients had no dysphagia, and 14% had no improvement with treatment. Importantly, the median time to clinical improvement was 6 weeks following the initiation of chemoradiation. This delay in treatment response is thought to be due to reactive esophagitis that results from treatment even as the tumor decreases in size, which adversely affects the oral intake of food. Because of this, patients with an expected survival of 3 to 4 months should preferably be evaluated for palliation using an alternative method, as these patients would experience a very limited benefit from chemoradiation for palliative intent.
Brachytherapy refers to the placement of interstitial or intracavitary radioactive sources to facilitate the delivery of radiation doses to tumors, with relative sparing of surrounding tissues. High—dose-rate brachytherapy involves the placement of radiation seeds via blind-ended afterloading catheters for short periods of time. Although high—dose-rate brachytherapy is used in many centers for airway tumors, this therapy has not gained the same popularity for esophageal cancer. We have found the afterload catheters currently approved by the Food and Drug Administration to be cumbersome and more difficult to place than those approved for the airway. Treatment response time is also slower than that seen with PDT. A recent randomized study from Sweden comparing stent insertion and brachytherapy demonstrated a more rapid relief of dysphagia in stent patients, with improved dysphagia scores at 1 month.12 Median survival was similar for both groups (132 vs. 109 days, stent vs. brachytherapy).