Esophageal carcinoma is a cruel disease. Patients often experience progressive dysphagia, cachexia, and a variety of symptoms related to metastases. Notwithstanding recent advances in surgical and oncological care, the 5-year survival is abysmal with many patients dying within a few months. The emphasis on care is still very much palliative with dysphagia being a significant issue in over 50% of incurable cases.1
Although surgery has been used for palliation,2 endoscopic methods are the mainstay of therapy. Laser,3 argon plasma coagulation,4 photodynamic therapy,5 brachytherapy,6 local injection of alcohol,7 and antineoplastic drugs8 have all been used but have not become popular due to either relative lack of efficacy or logistic difficulties and expense. Placement of self-expanding metal or rigid silicone stents has thus become standard therapy in these patients. Palliative chemotherapy and radiotherapy also have a role although relief of dysphagia using these techniques is much slower. Due to tissue edema, the dysphagia may actually become worse before getting better.
Once the decision is made to place a stent, a bewildering array of types confronts the endoscopist. In keeping with much else in medicine, the availability of many different stent types attests to the absence of demonstrable superiority of one design. Instead, interventional endoscopists often find themselves listening to a variety of sales people, arriving on the doorstep with ever more nuanced stent designs and attractive pictures and even DVDs, but rarely with any objective data of improved efficacy. There is evidence, nonetheless, that, compared with uncovered metal stents, covered ones prevent tumor ingrowth without substantially raising migration rates.9 Nonetheless, migration of covered esophageal stents remains a significant problem. Particularly in those placed in the distal esophagus, stent migration occurs in a substantial minority of patients. There is also a recently reported prospective study showing that self-expanding silicone stents (Polyflex, Boston Scientific, Massachusetts, USA), while providing comparable palliation, migrate more readily than their metal counterparts (Ultraflex, Boston Scientific, Massachusetts, USA and Niti-S, Taewong Medical, Seol, Korea).10
It is against this background that a Korean group in this edition of the Journal,11 working in a single center, compared prospectively two types of Niti-S stents—the covered variety, and the newer double-layered stent. This latter covered stent, with its double-layer configuration, is designed to prevent both stent migration and tumor ingrowth. The inner layer is covered but the outer layer is uncovered to enable better bedding into the esophageal wall. The results were a little surprising. The double-layered stent led to a nonsignificant reduction in tumor overgrowth (0 out of 17 vs 5 out of 19), but there was no difference in migration rates. In fact only one patient in either group experienced stent migration. This compares favorably to other series.9,10 What are harder to interpret are the data regarding the complications and deaths. One patient in the double-layer group, who was then excluded from the complications analysis, had to have the stent removed surgically after a perforation occurred during its placement. He died 54 days later from disease progression with a gastrostomy being used for nutritional support. A further four patients (three in the covered group and one in the double-layer group) died of ‘stent-related’ causes. These four patients were not excluded from those analyzed for complications. It would be useful to know the exact timing and cause of death in these patients and whether any of the listed complications contributed to their demise.
The analysis of the complications is also a little curious in that they were all lumped together and then analyzed statistically. The ‘nondysphagia-related’ complications which were unique to the covered group were gastroesophageal reflux (2), pneumonia (1), and hemorrhage (2); the clinical sequelae of these complications are not stated. One patient in the double-layer group developed a fistula—one would suspect that this may have had a very significant clinical impact, but again the clinical course is not stated. In addition, the clinical effects of tumor overgrowth (five in the covered group) and stent migration (one in the covered group) would have been useful to know in terms of gauging the clinical significance of the complications, and for determining whether the statistically significant advantage in the double-layer group was clinically important. Did the covered group spend more days in hospital after stent placement? Was there a difference in terms of need for supplemental nutritional support (tube feeding, gastrostomy, jejunostomy), or intravenous fluids between the two groups?
In terms of palliation of dysphagia, the two groups were very comparable with 1 week and 1 month data showing substantial improvement in dysphagia scores. The median survival of the two groups was 62 and 74 days. Information that would have been important to know is how many patients died within a few days after stent placement. Placing a stent in a moribund patient with only days to live is hard to justify both from a palliative point of view and in terms of cost-effectiveness.
So what other questions should be asked of that enthusiastic sales representative when confronted by the latest stent being caressed by those finely manicured fingers? The Korean study does not directly look at the issues of removability, antireflux valves, radial force, stent diameters and lengths, antimigratory flanges, and anchoring devices. Removability is much less of an issue in these patients than those with benign strictures, although it may become important if systemic or local therapy results in significant tumor shrinkage. For example, in another recent, prospective study from Korea,12 24 patients in whom Niti-S stents were placed a week before commencement of radiotherapy and then removed 3 weeks after its commencement were compared with 23 patients who received the same treatment but in whom the stents were not removed. Stent removal was possible in all 24 patients in whom the covered Niti-S stents was placed. These patients had better dysphagia—progression—free and overall survival compared with patients in whom the stents were left in place. It is likely, however, that the newer double-layered stent with its uncovered external layer would be less removable than the covered one but this is conjectural as the policy of removing the stents was not used in the current study. Similarly, the expandable plastic stent (Polyflex) could also be used in this manner. A biodegradable stent would be useful in this context to provide a dysphagia-free window while the effects of radiotherapy occur which would obviate the need for subsequent elective stent removal. There is only one biodegradable stent available in Australia and experience is very limited with this device.
Antireflux valves may be helpful in preventing symptomatic reflux in stents straddling the lower esophageal sphincter but the data are mixed.13,14 Radial force is an important consideration if patients have been previously treated with radiotherapy and in tumors bearing a close relationship to the trachea or major bronchi. A stent with high radial force may lead to fistula formation and airway compromise in such patients. An existing fistula precludes the use of uncovered stents; the double-layered stent may not effectively close a fistula as there is potential for leakage between the two layers. Finally, pain after the procedure, which was not discussed in the Korean study, necessitates admission to hospital in many patients and anecdotally is more likely to occur in stents of larger diameter. On the other hand, these larger stents may well be less prone to food bolus obstruction and migration (when placed across the gastroesophageal junction). Similarly, a longer stent may be less prone to tumor ingrowth at its edges but is probably more likely to become blocked by a food bolus.
Other potentially important factors that contribute to successful stent placement and which are difficult to study formally are the level of technical support from industry—which can be important in low volume centers—and the ease of use of the stent delivery system. Polyflex stents, while easily removable, are relatively difficult to mount before deployment and the rigid, large diameter delivery tube often makes them much harder to place compared with self-expandable metal stents (SEMS). Notwithstanding these caveats, the complication profile and efficacy of the double-layered Niti-S stent seen in this study compare favorably with those of other SEMS and support data from an earlier open-label study of 42 patients in which the Niti-S stent was used.15 The use of this stent appears to be effective for palliation of inoperable esophageal cancer and may provide superior results to other covered SEMS, although larger multicenter studies will be needed to confirm these preliminary findings.