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Management of inoperable malignant oesophageal strictures with fully covered WallFlex® stent: A multicentre prospective study
Digestive and Liver Disease 46 (2014) 1093–1098
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Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Digestive Endoscopy
Management of inoperable malignant oesophageal strictures with fully covered WallFlex® stent: A multicentre prospective study Alessandro Repici a,∗ , Manol Jovani a , Cesare Hassan a , Biagio Solito b , Roberto Di Mitri c , Federico Buffoli d , Giovanni Macrì e , Diego Fregonese f , Vincenzo Cennamo g , Mario De Bellis h , Andrea Anderloni a , Peter D. Siersema i a
Humanitas Research Hospital, Rozzano, Milan, Italy Santa Chiara Hospital, Pisa, Italy c Civic Hospital, Palermo, Italy d Cremona Hospital, Cremona, Italy e Acireale Hospital, Acireale, Italy f Camposampiero Hospital, Italy g S. Orsola-Malphigi Hospital University of Bologna, Bologna, Italy h National Cancer Institute, G. Pascale Foundation – IRCCS, Naples, Italy i University Medical Center Utrecht, Utrecht, Netherlands b
a r t i c l e
i n f o
Article history: Received 22 May 2014 Accepted 16 August 2014 Available online 26 September 2014 Keywords: Advanced oesophageal cancer Nutrition Palliation Self-expanding metal stent SEMS
a b s t r a c t Background: The majority of currently available oesophageal metal stents are partially covered to reduce migration risk. Preliminary experiences with fully covered stents seem to indicate an increased risk of migration in patients treated for malignant dysphagia. The aim of our study was to determine, in this setting, the safety and efficacy of a new, recently introduced stent with anti-migration proprieties. Methods: We designed a prospective, multicentre, non-randomized, follow-up study in nine tertiary referral centres. Eighty-two patients with dysphagia due to inoperable or metastatic oesophageal cancer were included. In all of them the fully covered WallFlex® stent was placed. Main outcome measurements included functional outcome, recurrent dysphagia, complications, and mortality. Results: Dysphagia score improved from a median of 3, before stenting, to 1 at 4 weeks after stent placement (P < 0.001). Perforation occurred in 1 patient after 39 days, while bleeding was reported in 3. In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (N = 10, 12.2%), tissue overgrowth (N = 7; 8.5%), and food impaction (N = 2; 2.4%). Conclusions: Placement of the fully covered WallFlex® stent resulted in safe and effective palliation of malignant dysphagia, with migration and tissue overgrowth rates comparable to previously reported data on partially covered stents. © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Oesophageal cancer is the eighth most common malignant disorder and the sixth on the list of cancer-related mortality, with a 5-year survival rate of 10–15% [1,2]. Despite recent advances in curative treatment, more than 50% of the patients have inoperable disease at presentation [3]. For these patients, palliative stent
∗ Corresponding author at: Digestive Endoscopy Unit, Humanitas Research Hospital, Via Manzoni 56, Rozzano, Milano, Italy. Tel.: +39 0282242579; fax: +39 0282244590. E-mail address: [email protected] (A. Repici).
placement is a well-accepted and effective endoscopic treatment option to relieve dysphagia [4,5]. Recurrent dysphagia after stent placement is a frequently encountered problem, occurring in 30–50% of patients, mainly due to tissue in- or overgrowth, stent migration, and food bolus impaction [6]. This relatively high frequency of recurrent dysphagia has resulted in efforts to improve stent design with the aim of reducing the incidence of stent obstruction and migration. Compared with partially covered stents, newer fully covered metal stents may be associated with less tissue ingrowth from malignant or granulation tissue and subsequent stenosis, and may be removable even after several weeks. However, the trade-off may be more frequent migration.
http://dx.doi.org/10.1016/j.dld.2014.08.037 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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Recently, the new fully covered WallFlex® stent (Boston Scientific, Natick, MA) has been developed with the indication for malignant dysphagia. Limited data are available in the literature on the performance of this stent in the management of malignant dysphagia. This multicentre, prospective study was undertaken to assess the technical and clinical success, as well as the complication rate, using the fully covered WallFlex® in patients with dysphagia due to primary inoperable oesophageal cancer. 2. Patients and methods Between January 2010 and December 2011, 82 consecutive patients with dysphagia due to an oesophageal malignant stricture, who met inclusion criteria and provided written informed consent, were treated with the fully covered WallFlex® stent. Inclusion criteria were dysphagia due to inoperable malignant obstruction of the oesophagus or gastro-oesophageal junction (i.e. local tumour infiltration, distant metastases, or poor general conditions). Exclusion criteria were evidence of tumour within 2 cm of the upper oesophageal sphincter, a tumour covering less than 50% of the oesophageal circumference, evidence of oesophago-tracheal fistula or tracheal invasion at radiological examinations, Karnofsky status < 50, previous upper gastrointestinal surgery, or treatment with oesophageal stent for the same condition. Nine centres from Italy and The Netherlands, participated in the study (Appendix A). All centres were active in the recruitment process and a mean of nine patients were treated in each centre. The Medical Ethic Committees of all participating hospitals approved the study and all patients gave informed consent. Patients were evaluated before stent placement, 14 days later, and at 4-week intervals after stent placement, until death. Evaluations were performed by clinical examination or scheduled telephone interviews of the patient or their caregivers and included the following: (1) ability to eat and/or swallow, as assessed by the dysphagia score (graded as: 0 = ability to eat a normal diet; 1 = ability to eat some solid food; 2 = ability to eat some semisolids only; 3 = ability to swallow liquids only; and 4 = complete dysphagia); (2) general health, as assessed by the World Health Organization performance score (graded as: 0 = normal activity; 1 = symptomatic but completely ambulatory; 2 = in bed less than 50% of time; 3 = in bed more than 50% of time; and 4 = 100% bedridden); and (3) specific symptoms such as pain and regurgitation. 2.1. Study endpoints The primary endpoint was recurrent dysphagia, defined as occurrence of tissue ingrowth or overgrowth caused by malignant or non-malignant tissue, stent migration, or food impaction leading to obstructive symptoms. Secondary endpoints were technical success, complications, and survival. Technical success was defined as ease of placement of the stent at the desired location verified by fluoroscopy and/or endoscopy. Complications were characterized as major or minor. Major complications were defined as life-threatening or severe complications for which an endoscopic intervention or hospitalization was required, and included perforation, haemorrhage, fistula, aspiration-pneumonia, and severe pain. Minor complications were defined as not life-threatening or mild-to-moderately severe complications that could be treated conservatively with no need for hospitalization or endoscopic reintervention, and included mild pain and gastroesophageal reflux. Survival included 30-day mortality and long-term survival.
Fig. 1. Endoscopic view of a correctly deployed fully-covered WallFlex® stent.
2.2. Stent placement The patients were placed in the left lateral position and were sedated using deep or conscious sedation at the discretion of the endoscopist and anaesthesiologist at each institution. The upper tumour margin was marked by external skin markers or using a submucosal injection of Lipiodol, and fluoroscopy was used to place a guidewire across the lesion and then far away into the stomach. Tumour length was measured by endoscopically assessing the upper and lower extremities of the neoplasia. Alternatively, tumour length was estimated radiologically after contrast medium injection. For cases in which it was not feasible to transverse the tumour, even with an extra-slim endoscope, careful mechanical dilation up to 10 mm was performed before stent placement. A stent measuring 2–4 cm longer than the stricture was chosen to allow for a 1-cm to 2-cm extension above and below the proximal and distal tumour borders. Endoscopy was repeated to ensure adequate placement and full deployment of the stent. All patients were placed on standard dose proton pump inhibitors. Pain medications were prescribed for oral administration when needed. 2.3. Stent characteristics The stent is made of a multiple wire braided of nickel-titanium alloy (Nitinol) and has a full Permalume silicone internal covering with progressive step-flared ends (Fig. 1); the body diameters of the two available stent versions were 18 mm and 23 mm, and the flange diameters were 23 mm and 28 mm. The stent is available in three lengths: 10 cm, 12 cm, and 15 cm. A removal suture at the proximal end can be used to pull the stent and reposition or remove it in case of need. The stent may be reconstrained up to 75% of deployment and twice during the initial stent placement procedure (Fig. 2). 2.4. Statistical analysis The following variables were included to assess the outcome: (1) clinical characteristics (age, gender, WHO performance score, dysphagia score before stent placement, tumoural length, location, histology, and previous radiation and/or chemotherapy); (2) results and survival (technical success, WHO score and dysphagia score after stent placement, survival, and cause of death); and (3) complications and recurrent dysphagia. Results are expressed as mean ± standard deviation or median, as appropriate, while survival was expressed as median. Differences in dysphagia score and WHO performance score before and 4 weeks after stent placement were analysed by the Wilcoxon rank
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Table 1 Clinical characteristics of 82 patients treated with a WallFlex® esophageal stent for palliation of malignant dysphagia. Characteristics
Patients N = 82
Median age, (range) Male N (%) Median dysphagia score before treatment (range) Median who performance score before treatment (range) Median tumour length, cm (range)
56 56 3 1 6
Tumour location Upper third Middle Lower Across GEJ
11 (13.4%) 26 (31.7%) 31 (37.8%) 14 (17.1%)
Tumour histology Adenocarcinoma Squamous cell carcinoma Unknown
49 (59.7%) 31 (37.8%) 2 (2.4%)
Prior radiation and/or chemotherapy (N = 30) Chemotherapy Radiation Both
17 (56.7%) 7 (23.3%) 6 (20%)
(37–85) (68%) (2–4) (0–3) (3–12)
WHO, World Health Organization; GEJ, gastroesophageal junction.
frequently reported post-procedural symptom (7/82, 8.5%), and was easily treated by oral or intravenous non-narcotic analgesics in all cases (Table 2). 3.2. Functional outcome Twelve patients (14.6%) died from disease progression within 4 weeks of stent placement; in all of these, an improvement of the dysphagia score had been reported. The dysphagia score improved in surviving patients from a median of 3 (range 2–4) to a median of 1 (range 1–2; P < 0.001) at both 14 days and 4 weeks after stent placement. After stent placement, 24 patients (29.2%) received the following treatments: additional palliative chemotherapy only (n = 14), radiotherapy only (n = 2), or a combination of both (n = 8). Most patients (49, 59.7%) lived longer than 4 weeks but died within 6 months from stent placement as a result of tumour progression. Median survival after stent placement was 144 ± 17 days (range: 19–218 days). Twenty-one patients (25.6%) were still alive at the end of a follow-up of at least 6 months, and most of them (16/21, 76.2%) were free of dysphagia. 3.3. Complications and recurrent dysphagia Fig. 2. Radiologic view of a correctly deployed fully-covered WallFlex® stent. Ingestion of contrast medium shows restored esophageal patency.
sum test. All analyses were performed on an intent-to-treat basis. A P < 0.05 was considered statistically significant. All analyses were conducted with SPSS, version 14.0 (SPSS Inc., Chicago, IL). 3. Results 3.1. Clinical and procedural characteristics The clinical characteristics of the 82 patients treated with WallFlex® oesophageal stent are shown in Table 1. Overall, WallFlex® stent was successfully placed in 81 patients, while in one case stent release was too distal and required a second stent placement in the same procedure after removal of the first stent. Pre-stent placement dilation was performed in 15 patients (18.2%). Temporary mild-to-moderate pain was the most
In total, major complications occurred in 4 patients (4.9%). Two of them (2.4%) developed late severe bleeding requiring blood Table 2 Complications and recurrent dysphagia in 82 patients after placement of a WallFlex® stent. Complication Major complications Perforation Haemorrhage Aspiration
Patients N (%) 4 (4.9) 1 (1.2) 3 (3.7) 0 (0)
Minor complications Mild retrosternal pain Gastroesophageal reflux
14 (17) 8 (9.7) 8 (9.7)
Recurrent dysphagia Tissue ingrowth/overgrowth Food bolus impaction Stent migration
19 (23.1) 7 (8.5) 2 (2.4) 10 (12.1)
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transfusion (8 and 11 weeks after stent placement). A third patient developed a fatal haemorrhage after 3 months from stent placement, a condition that was probably due to an aorto-oesophageal fistula. One late perforation occurred 39 days after stent placement. Due to the poor clinical condition of the patient and in accordance with this patient’s will, only supportive care was provided after the CT scan had shown signs of perforation, and the patient died three days later. Minor complications, such as retrosternal pain and symptoms referable to gastro-oesophageal reflux, were observed in 8 patients (9.8%). In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (n = 10, 12.2%), tissue overgrowth (n = 7, 8.5%), and food impaction (n = 2, 2.4%). Stent migration was recorded in 6 patients with a stricture at the gastroesopheageal junction (one was undergoing palliative radio-chemotherapy) and in 4 patients with mid-oesophageal stricture. In all cases the stent was not removed from the stomach, and a second stent was placed in the oesophagus in all but one patient who was showing significant tumour response to palliative radio-chemotherapy with improvement of dysphagia. Tumour overgrowth was observed at the proximal end of the stent in 3 cases, at the distal end in two cases, and at both ends in 2 cases. Two of these patients were successfully treated with argon plasma coagulation (APC), 2 received a second stent, 1 refused further treatment, and 1 was left untreated because of the advanced stage of the disease and very short life expectancy. Food impaction was successfully treated by endoscopic clearance in both patients, with no need for stent removal and no recurrence of impaction. We performed a univariate analysis of patients treated with radiation and/or chemotherapy before or after stent placement. This analysis showed that the occurrence of complications (hazard ratio [HR] 1.52, 95% CI 0.68–3.04) and recurrence of dysphagia (HR 1.56, 95% CI 0.88–2.78) were not associated with prior or subsequent radiation and/or chemotherapy.
4. Discussion Various types of self-expandable metal stents (SEMS), either fully covered or partially covered have been used for the palliation of malignant dysphagia [7–20]. Dysphagia relief has been reported in 80–100% of patients in most of these studies. The major limit of the partially covered SEMS has been recurrent dysphagia due to tissue in- and overgrowth in the anchored stent [6,20]. Fully covered SEMS have been designed to overcome such shortcomings with the assumption that the complete covering would greatly reduce tissue ingrowth and, consequently, reduce recurrent dysphagia (7–10). However, a well-known and predictable drawback of the fully covered design has been an increase in the rate of migration, ranging from 20% to 39% in most studies [8,9,13,17]. Lower rates of migration, in the order of 7–12%, have been reported with some new fully covered SEMS [7,12,21,22]. A new, fully covered stent (WallFlex® ; Boston Scientific, Natick, MA) has recently been developed with internal covering and a dog-bone shape design aimed at reducing recurrent dysphagia by preventing migration and tissue in and overgrowth. Data on the performance of this stent in the management of malignant dysphagia are very limited. The FC WallFlex® stent was recently evaluated in a small, singlecentre, prospective study of 48 patients with both benign and malignant dysphagia [7]. For malignant strictures it showed good improvement in the dysphagia scores with a recurrent dysphagia rate of only 15%, and low rates of migration (9%), bleeding (6%), and tissue overgrowth (3%). Confirmed fistula formation was observed in two patients (6%), with another two having deep ulcers,
probably owing to a high radial force of the stent [7]. Another recent, small, single-centre, prospective study evaluated the fully covered WallFlex® stent in 20 patients with various indications, such as perforations, strictures and fistulas, both benign and malignant [8]. An overall response rate of 55% was observed (67% for malignant diseases) with an overall migration rate of 29%. Our prospective, multicentre, non-randomized, open-label study was therefore performed to evaluate technical feasibility, clinical outcome, and complication rates of the placement of a new fully covered WallFlex® stent as palliative treatment in a cohort of 82 consecutive patients with dysphagia from inoperable primary oesophageal cancer. In this study, we demonstrate that the fully covered WallFlex® stent provides good relief of malignant dysphagia and is associated with low rates of migration and other complications. Similarly to previous reports for other stents in malignant strictures [9–20], stent placement in our cohort was safe and easy in almost all cases (98.8%), with only a minority of patients (18.2%) requiring pre-stent placement dilation. The fully covered WallFlex® stent provided a good relief of malignant dysphagia, reducing the score from a median of 3 to a median of 1 (P < 0.001) both at 14 days and 4 weeks after stent placement, in line with previous studies. Recurrent dysphagia was observed in 19 patients (23.1%) and was caused by stent migration (N = 10; 12.2%), tissue overgrowth (N = 7; 8.5%), or food impaction (N = 2; 2.4%). The overall dysphagia recurrence rate with SEMS, for any reason, ranges between 12% and 49% in the literature [10–18,23]. Even though our migration rate is slightly higher than a previous experience with the same fully covered WallFlex® stent, which found a recurrence rate of 15% [7], it falls neatly within the rates of recurrent dysphagia reported in the literature. More specifically, the migration rate observed in our study is comparable with the rates found in the most favourable experiences with other fully covered stent designs [7,12,19–22] and, more interestingly, is similar to the migration rates reported with the partially covered oesophageal SEMS [10,15–18,20–22]. A fact worth mentioning is that most of the stent migrations registered in our study (7 out of 10) occurred in patients with strictures located across the gastroesophageal junction, a location predisposing to stent migration, as data from the literature suggest [12,14,20–24]. These favourable migration rates are likely the result of the new design of the stent, i.e., internal covering and a doublefunnel shape that stabilizes it in the stricture [7–9,24]. As expected from the fully covered stent design, we did not observe any case of tissue ingrowth [13,20], whilst our rate of tissue overgrowth is comparable to the rates reported with fully covered SEMS or fully covered self expandable plastic stents, which range between 0% and 38% [12–14,18,22–24], and to previous experiences with the WallFlex® stent which ranged from 0% to 19% [7–9]. Four of these patients were successfully treated with either APC [12] or placement of a second stent [10,12], while one refused further treatment and the other was left untreated for critical clinical conditions. The low rate of food obstruction observed in our study (2.4%) is partly due to the presence of the internal covering of the WallFlex® stent, and partly to the careful dietary instructions given to our patients [20]. A total of four patients (7.6%) experienced major complications, including three (3.7%) late severe haemorrhage episodes and one late perforation. Two of the patients that experienced bleeding required blood transfusion, while the other died from massive haemorrhage, likely from an aorto-oesophageal fistula. In all three cases the largest stent type (23 mm × 28 mm × 125 mm) had been used. In a previous study, the larger diameter of the Gianturco Zstent was associated with higher rates of major complication when compared to stents with smaller diameter [23]. The small number of major complications recorded in our study does not allow us to determine if the association between these complications
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and a larger diameter is also true for the fully covered WallFlex® stent. Only supportive care was given to the patient who experienced perforation, in consideration of his will and poor clinical conditions, and he died shortly after. Therefore, we had two stentrelated deaths in our study (2.4%). Our rates of major complications are well within the range of those observed in other studies with both fully and partially covered SEMS, which ranged from 0 to 40%, and in particular bleeding, which ranged from 0% to 18%, and perforation/fistula formation, which ranged from 0% to 15% in the aforementioned studies. Therefore, the overall recurrent dysphagia and major complication rates with the new FC WallFlex® stent are in the lower-end of the spectrum of complication rates observed with other SEMS. In particular, the low migration rate of the fully covered WallFlex® stent compares very well not only with the migration rates of other fully covered SEMS, but also with the migration rates of the partially covered SEMS. Nearly one-third of our patients had received radiotherapy and/or chemotherapy prior or subsequent to stent placement. Data regarding the effect of prior radiochemotherapy on the risk of complications after SEMS placement are conflicting, with some reporting an increased risk [7,25], particularly for definitive radiochemotherapy [11], and others not finding any additional risk factor in these prior therapies [26]. A univariate analysis of our data found no association between the rate of complications and/or recurrence of dysphagia with either prior or subsequent radio and/or chemotherapy. Since complications from radiochemiotherapy are usually dose-dependent [11], these results probably reflect the lower palliative dose regimens of radio and/or chemotherapy administered to the patients included in our study. Our study has several strengths. First, differently from several previous studies, we included a strongly homogeneous population of patients, in terms of clinical indication and stent design. Second, this study includes the largest number of patients treated with the new fully covered WallFlex® stent, followed up for a relatively long time (>5 months) and with no patient lost to follow-up. Finally, its prospective and multicentre design allows for a better estimation of adverse events and a greater reproducibility of the results in the general clinical practice, as opposed to previous retrospective designs and single-centre experiences. Among the weaknesses of our study we recognize the non-randomized, open-label design and the lack of comparison with other treatment options. Future well-designed, randomized, controlled clinical trials will allow to better define the role of the new WallFlex® stent in comparison to other therapeutic/palliative strategies for the management of oesophageal cancer. Moreover, well-designed, homogeneous studies will be necessary to adequately assess the efficacy and safety of the fully covered WallFlex® stent in other oesophageal diseases as well. Such conditions may include benign dysphagia (such as post-surgical or post-radiotherapy oesophageal strictures) or else the presence of oesophago-tracheal fistula (both benign or malignant). In this last setting SEMS placement has proven to be an excellent treatment option [10,24]. In conclusion, our study demonstrates that the fully covered oesophageal WallFlex® stent is safe and effective for the palliation of dysphagia from inoperable primary oesophageal cancer strictures, with high technical and clinical success, as well as low complication and migration rates.
Conflict of interest Dr. A. Repici: serves as Consultant for Boston Scientific; Dr. P.D. Siersema: serves as Consultant for Boston Scientific. All other authors have no conflicts of interest or financial ties to disclose.
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Appendix A. Participating centres Humanitas Research Hospital, Rozzano, Milan, Italy Santa Chiara Hospital, Pisa, Italy Civic Hospital of Palermo, Palermo, Italy Cremona Hospital, Cremona, Italy Acireale Hospital, Acireale, Italy Camposampiero Hospital, Camposampiero, Italy S. Orsola-Malphigi Hospital, Bologna, Italy National Cancer Institute, G. Pascale Foundation, Naples, Italy University Medical Center Utrecht, Utrecht, Netherlands References [1] Parkin DM, Bray F, Ferlay J. Global cancer statistic 2002. CA: A Cancer Journal for Clinician 2005;55:74–108. [2] Pisani P, Parkin DM, Bray F, et al. Estimates of the worldwide mortality from 25 cancers in 1990. International Journal of Cancer 1999;83:18–29. [3] Stein Hj, Siewert JR. Improved prognosis of resected oesophageal cancer. World Journal of Surgery 2004;28:520–5. [4] Homs MY, Kuipers EJ, Siersema PD. Palliative therapy. Journal of Surgical Oncology 2005;92:246–56. [5] Siersema PD. Treatment options for oesophageal strictures. Nature Clinical Practice Gastroenterology & Hepatology 2008;5:142–52. [6] Repici A, Rando G. Expandable stent for malignant dysphagia. Techniques in Gastrointestinal Endoscopy 2008;10:175–83. [7] Hirdes MM, Siersema PD, Vleggaar FP. A new fully covered metal stent for the treatment of benign and malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2012;75:712–8. [8] Wagh MS, Forsmark CE, Chauhan S, et al. Efficacy and safety of a fully covered oesophageal stent: a prospective study. Gastrointestinal Endoscopy 2012;75:678–82. [9] Siddiqui AA, Sarkar A, Beltz S, et al. Placement of fully covered selfexpandable metal stents in patients with locally advanced oesophageal cancer before neoadjuvant therapy. Gastrointestinal Endoscopy 2012;76: 44–51. [10] van Heel NC, Haringsma J, Boot H, et al. Comparison of 2 expandable stents for malignant oesophageal disease: a randomized controlled trial. Gastrointestinal Endoscopy 2012;76:52–8. [11] Didden P, Spaander MC, Kuipers EJ, et al. Safety of stent placement in recurrent or persistent oesophageal cancer after definitive chemoradiotherapy: a case series. Gastrointestinal Endoscopy 2012;76:426–30. [12] Lazaraki G, Katsinelos P, Nakos A, et al. Malignant oesophageal dysphagia palliation using insertion of a covered Ultraflex stent without fluoroscopy: a prospective observational study. Surgical Endoscopy 2011;25: 628–35. [13] Uitdehaag MJ, Siersema PD, Spaander MC, et al. A new fully covered stent with antimigration properties for the palliation of malignant dysphagia: a prospective cohort study. Gastrointestinal Endoscopy 2010;71:600–5. [14] Uitdehaag MJ, van Hooft JE, Verschuur EM, et al. A fully-covered stent (AlimaxxE) for the palliation of malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2009;70:1082–9. [15] van Boeckel PG, Siersema PD, Sturgess R, et al. A new partially covered metal stent for palliation of malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2010;72:1269–73. [16] van Boeckel PG, Repici A, Vleggaar FP, et al. A new metal stent with a controlledrelease system for palliation of malignant dysphagia: a prospective, multicenter study. Gastrointestinal Endoscopy 2010;71:455–60. [17] Eloubeidi MA, Lopes TL. Novel removable internally fully covered selfexpanding metal oesophageal stent: feasibility, technique of removal, and tissue response in humans. American Journal of Gastroenterology 2009;104:1374–81. [18] Conio M, Repici A, Battaglia G, et al. A randomized prospective comparison of self-expandable plastic stents and partially covered self-expandable metal stents in the palliation of malignant oesophageal dysphagia. American Journal of Gastroenterology 2007;102:2667–77. [19] Conigliaro R, Battaglia G, Repici A, et al. Polyflex stent for malignant oesophageal and oesophagogastric stricture: a prospective, multicentric study. European Journal of Gastroenterology and Hepatology 2007;19:195–203. [20] Vleggaar FP, Siersema PD. Expandable stents for malignant oesophageal disease. Gastrointestinal Endoscopy Clinics of North America 2011;21:377–88, vii. [21] Verschuur EM, Homs MY, Steyerberg EW, et al. A new oesophageal stent design (Niti-S stent) for the prevention of migration: a prospective study in 42 patients. Gastrointestinal Endoscopy 2006;63:134–40. [22] Verschuur EM, Repici A, Kuipers EJ, et al. New design oesophageal stents for the palliation of dysphagia from oesophageal or gastric cancer cardia cancer: a randomized trial. American Journal of Gastroenterology 2008;103: 304–12. [23] Verschuur EM, Steyerberg EW, Kuipers EJ, et al. Effect of stent size on complications and recurrent dysphagia in patients with oesophageal or gastric cardia cancer. Gastrointestinal Endoscopy 2007;65:592–601.
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[24] Seven G, Irani S, Ross AS, et al. Partially versus fully covered selfexpanding metal stents for benign and malignant oesophageal conditions: a single center experience. Surgical Endoscopy 2013;27: 2185–92. [25] Lecleire S, Di Fiore F, Ben-Soussan E, et al. Prior chemoradiotherapy is associated with a higher life-threatening complication rate after palliative insertion of
metal stents in patients with oesophageal cancer. Alimentary Pharmacology and Therapeutics 2006;23:1693–702, 15;. [26] Homs MY, Hansen BE, van Blankenstein M, et al. Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma. European Journal of Gastroenterology and Hepatology 2004;16:163–70.
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Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Digestive Endoscopy
Management of inoperable malignant oesophageal strictures with fully covered WallFlex® stent: A multicentre prospective study Alessandro Repici a,∗ , Manol Jovani a , Cesare Hassan a , Biagio Solito b , Roberto Di Mitri c , Federico Buffoli d , Giovanni Macrì e , Diego Fregonese f , Vincenzo Cennamo g , Mario De Bellis h , Andrea Anderloni a , Peter D. Siersema i a
Humanitas Research Hospital, Rozzano, Milan, Italy Santa Chiara Hospital, Pisa, Italy c Civic Hospital, Palermo, Italy d Cremona Hospital, Cremona, Italy e Acireale Hospital, Acireale, Italy f Camposampiero Hospital, Italy g S. Orsola-Malphigi Hospital University of Bologna, Bologna, Italy h National Cancer Institute, G. Pascale Foundation – IRCCS, Naples, Italy i University Medical Center Utrecht, Utrecht, Netherlands b
a r t i c l e
i n f o
Article history: Received 22 May 2014 Accepted 16 August 2014 Available online 26 September 2014 Keywords: Advanced oesophageal cancer Nutrition Palliation Self-expanding metal stent SEMS
a b s t r a c t Background: The majority of currently available oesophageal metal stents are partially covered to reduce migration risk. Preliminary experiences with fully covered stents seem to indicate an increased risk of migration in patients treated for malignant dysphagia. The aim of our study was to determine, in this setting, the safety and efficacy of a new, recently introduced stent with anti-migration proprieties. Methods: We designed a prospective, multicentre, non-randomized, follow-up study in nine tertiary referral centres. Eighty-two patients with dysphagia due to inoperable or metastatic oesophageal cancer were included. In all of them the fully covered WallFlex® stent was placed. Main outcome measurements included functional outcome, recurrent dysphagia, complications, and mortality. Results: Dysphagia score improved from a median of 3, before stenting, to 1 at 4 weeks after stent placement (P < 0.001). Perforation occurred in 1 patient after 39 days, while bleeding was reported in 3. In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (N = 10, 12.2%), tissue overgrowth (N = 7; 8.5%), and food impaction (N = 2; 2.4%). Conclusions: Placement of the fully covered WallFlex® stent resulted in safe and effective palliation of malignant dysphagia, with migration and tissue overgrowth rates comparable to previously reported data on partially covered stents. © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Oesophageal cancer is the eighth most common malignant disorder and the sixth on the list of cancer-related mortality, with a 5-year survival rate of 10–15% [1,2]. Despite recent advances in curative treatment, more than 50% of the patients have inoperable disease at presentation [3]. For these patients, palliative stent
∗ Corresponding author at: Digestive Endoscopy Unit, Humanitas Research Hospital, Via Manzoni 56, Rozzano, Milano, Italy. Tel.: +39 0282242579; fax: +39 0282244590. E-mail address: [email protected] (A. Repici).
placement is a well-accepted and effective endoscopic treatment option to relieve dysphagia [4,5]. Recurrent dysphagia after stent placement is a frequently encountered problem, occurring in 30–50% of patients, mainly due to tissue in- or overgrowth, stent migration, and food bolus impaction [6]. This relatively high frequency of recurrent dysphagia has resulted in efforts to improve stent design with the aim of reducing the incidence of stent obstruction and migration. Compared with partially covered stents, newer fully covered metal stents may be associated with less tissue ingrowth from malignant or granulation tissue and subsequent stenosis, and may be removable even after several weeks. However, the trade-off may be more frequent migration.
http://dx.doi.org/10.1016/j.dld.2014.08.037 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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Recently, the new fully covered WallFlex® stent (Boston Scientific, Natick, MA) has been developed with the indication for malignant dysphagia. Limited data are available in the literature on the performance of this stent in the management of malignant dysphagia. This multicentre, prospective study was undertaken to assess the technical and clinical success, as well as the complication rate, using the fully covered WallFlex® in patients with dysphagia due to primary inoperable oesophageal cancer. 2. Patients and methods Between January 2010 and December 2011, 82 consecutive patients with dysphagia due to an oesophageal malignant stricture, who met inclusion criteria and provided written informed consent, were treated with the fully covered WallFlex® stent. Inclusion criteria were dysphagia due to inoperable malignant obstruction of the oesophagus or gastro-oesophageal junction (i.e. local tumour infiltration, distant metastases, or poor general conditions). Exclusion criteria were evidence of tumour within 2 cm of the upper oesophageal sphincter, a tumour covering less than 50% of the oesophageal circumference, evidence of oesophago-tracheal fistula or tracheal invasion at radiological examinations, Karnofsky status < 50, previous upper gastrointestinal surgery, or treatment with oesophageal stent for the same condition. Nine centres from Italy and The Netherlands, participated in the study (Appendix A). All centres were active in the recruitment process and a mean of nine patients were treated in each centre. The Medical Ethic Committees of all participating hospitals approved the study and all patients gave informed consent. Patients were evaluated before stent placement, 14 days later, and at 4-week intervals after stent placement, until death. Evaluations were performed by clinical examination or scheduled telephone interviews of the patient or their caregivers and included the following: (1) ability to eat and/or swallow, as assessed by the dysphagia score (graded as: 0 = ability to eat a normal diet; 1 = ability to eat some solid food; 2 = ability to eat some semisolids only; 3 = ability to swallow liquids only; and 4 = complete dysphagia); (2) general health, as assessed by the World Health Organization performance score (graded as: 0 = normal activity; 1 = symptomatic but completely ambulatory; 2 = in bed less than 50% of time; 3 = in bed more than 50% of time; and 4 = 100% bedridden); and (3) specific symptoms such as pain and regurgitation. 2.1. Study endpoints The primary endpoint was recurrent dysphagia, defined as occurrence of tissue ingrowth or overgrowth caused by malignant or non-malignant tissue, stent migration, or food impaction leading to obstructive symptoms. Secondary endpoints were technical success, complications, and survival. Technical success was defined as ease of placement of the stent at the desired location verified by fluoroscopy and/or endoscopy. Complications were characterized as major or minor. Major complications were defined as life-threatening or severe complications for which an endoscopic intervention or hospitalization was required, and included perforation, haemorrhage, fistula, aspiration-pneumonia, and severe pain. Minor complications were defined as not life-threatening or mild-to-moderately severe complications that could be treated conservatively with no need for hospitalization or endoscopic reintervention, and included mild pain and gastroesophageal reflux. Survival included 30-day mortality and long-term survival.
Fig. 1. Endoscopic view of a correctly deployed fully-covered WallFlex® stent.
2.2. Stent placement The patients were placed in the left lateral position and were sedated using deep or conscious sedation at the discretion of the endoscopist and anaesthesiologist at each institution. The upper tumour margin was marked by external skin markers or using a submucosal injection of Lipiodol, and fluoroscopy was used to place a guidewire across the lesion and then far away into the stomach. Tumour length was measured by endoscopically assessing the upper and lower extremities of the neoplasia. Alternatively, tumour length was estimated radiologically after contrast medium injection. For cases in which it was not feasible to transverse the tumour, even with an extra-slim endoscope, careful mechanical dilation up to 10 mm was performed before stent placement. A stent measuring 2–4 cm longer than the stricture was chosen to allow for a 1-cm to 2-cm extension above and below the proximal and distal tumour borders. Endoscopy was repeated to ensure adequate placement and full deployment of the stent. All patients were placed on standard dose proton pump inhibitors. Pain medications were prescribed for oral administration when needed. 2.3. Stent characteristics The stent is made of a multiple wire braided of nickel-titanium alloy (Nitinol) and has a full Permalume silicone internal covering with progressive step-flared ends (Fig. 1); the body diameters of the two available stent versions were 18 mm and 23 mm, and the flange diameters were 23 mm and 28 mm. The stent is available in three lengths: 10 cm, 12 cm, and 15 cm. A removal suture at the proximal end can be used to pull the stent and reposition or remove it in case of need. The stent may be reconstrained up to 75% of deployment and twice during the initial stent placement procedure (Fig. 2). 2.4. Statistical analysis The following variables were included to assess the outcome: (1) clinical characteristics (age, gender, WHO performance score, dysphagia score before stent placement, tumoural length, location, histology, and previous radiation and/or chemotherapy); (2) results and survival (technical success, WHO score and dysphagia score after stent placement, survival, and cause of death); and (3) complications and recurrent dysphagia. Results are expressed as mean ± standard deviation or median, as appropriate, while survival was expressed as median. Differences in dysphagia score and WHO performance score before and 4 weeks after stent placement were analysed by the Wilcoxon rank
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Table 1 Clinical characteristics of 82 patients treated with a WallFlex® esophageal stent for palliation of malignant dysphagia. Characteristics
Patients N = 82
Median age, (range) Male N (%) Median dysphagia score before treatment (range) Median who performance score before treatment (range) Median tumour length, cm (range)
56 56 3 1 6
Tumour location Upper third Middle Lower Across GEJ
11 (13.4%) 26 (31.7%) 31 (37.8%) 14 (17.1%)
Tumour histology Adenocarcinoma Squamous cell carcinoma Unknown
49 (59.7%) 31 (37.8%) 2 (2.4%)
Prior radiation and/or chemotherapy (N = 30) Chemotherapy Radiation Both
17 (56.7%) 7 (23.3%) 6 (20%)
(37–85) (68%) (2–4) (0–3) (3–12)
WHO, World Health Organization; GEJ, gastroesophageal junction.
frequently reported post-procedural symptom (7/82, 8.5%), and was easily treated by oral or intravenous non-narcotic analgesics in all cases (Table 2). 3.2. Functional outcome Twelve patients (14.6%) died from disease progression within 4 weeks of stent placement; in all of these, an improvement of the dysphagia score had been reported. The dysphagia score improved in surviving patients from a median of 3 (range 2–4) to a median of 1 (range 1–2; P < 0.001) at both 14 days and 4 weeks after stent placement. After stent placement, 24 patients (29.2%) received the following treatments: additional palliative chemotherapy only (n = 14), radiotherapy only (n = 2), or a combination of both (n = 8). Most patients (49, 59.7%) lived longer than 4 weeks but died within 6 months from stent placement as a result of tumour progression. Median survival after stent placement was 144 ± 17 days (range: 19–218 days). Twenty-one patients (25.6%) were still alive at the end of a follow-up of at least 6 months, and most of them (16/21, 76.2%) were free of dysphagia. 3.3. Complications and recurrent dysphagia Fig. 2. Radiologic view of a correctly deployed fully-covered WallFlex® stent. Ingestion of contrast medium shows restored esophageal patency.
sum test. All analyses were performed on an intent-to-treat basis. A P < 0.05 was considered statistically significant. All analyses were conducted with SPSS, version 14.0 (SPSS Inc., Chicago, IL). 3. Results 3.1. Clinical and procedural characteristics The clinical characteristics of the 82 patients treated with WallFlex® oesophageal stent are shown in Table 1. Overall, WallFlex® stent was successfully placed in 81 patients, while in one case stent release was too distal and required a second stent placement in the same procedure after removal of the first stent. Pre-stent placement dilation was performed in 15 patients (18.2%). Temporary mild-to-moderate pain was the most
In total, major complications occurred in 4 patients (4.9%). Two of them (2.4%) developed late severe bleeding requiring blood Table 2 Complications and recurrent dysphagia in 82 patients after placement of a WallFlex® stent. Complication Major complications Perforation Haemorrhage Aspiration
Patients N (%) 4 (4.9) 1 (1.2) 3 (3.7) 0 (0)
Minor complications Mild retrosternal pain Gastroesophageal reflux
14 (17) 8 (9.7) 8 (9.7)
Recurrent dysphagia Tissue ingrowth/overgrowth Food bolus impaction Stent migration
19 (23.1) 7 (8.5) 2 (2.4) 10 (12.1)
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transfusion (8 and 11 weeks after stent placement). A third patient developed a fatal haemorrhage after 3 months from stent placement, a condition that was probably due to an aorto-oesophageal fistula. One late perforation occurred 39 days after stent placement. Due to the poor clinical condition of the patient and in accordance with this patient’s will, only supportive care was provided after the CT scan had shown signs of perforation, and the patient died three days later. Minor complications, such as retrosternal pain and symptoms referable to gastro-oesophageal reflux, were observed in 8 patients (9.8%). In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (n = 10, 12.2%), tissue overgrowth (n = 7, 8.5%), and food impaction (n = 2, 2.4%). Stent migration was recorded in 6 patients with a stricture at the gastroesopheageal junction (one was undergoing palliative radio-chemotherapy) and in 4 patients with mid-oesophageal stricture. In all cases the stent was not removed from the stomach, and a second stent was placed in the oesophagus in all but one patient who was showing significant tumour response to palliative radio-chemotherapy with improvement of dysphagia. Tumour overgrowth was observed at the proximal end of the stent in 3 cases, at the distal end in two cases, and at both ends in 2 cases. Two of these patients were successfully treated with argon plasma coagulation (APC), 2 received a second stent, 1 refused further treatment, and 1 was left untreated because of the advanced stage of the disease and very short life expectancy. Food impaction was successfully treated by endoscopic clearance in both patients, with no need for stent removal and no recurrence of impaction. We performed a univariate analysis of patients treated with radiation and/or chemotherapy before or after stent placement. This analysis showed that the occurrence of complications (hazard ratio [HR] 1.52, 95% CI 0.68–3.04) and recurrence of dysphagia (HR 1.56, 95% CI 0.88–2.78) were not associated with prior or subsequent radiation and/or chemotherapy.
4. Discussion Various types of self-expandable metal stents (SEMS), either fully covered or partially covered have been used for the palliation of malignant dysphagia [7–20]. Dysphagia relief has been reported in 80–100% of patients in most of these studies. The major limit of the partially covered SEMS has been recurrent dysphagia due to tissue in- and overgrowth in the anchored stent [6,20]. Fully covered SEMS have been designed to overcome such shortcomings with the assumption that the complete covering would greatly reduce tissue ingrowth and, consequently, reduce recurrent dysphagia (7–10). However, a well-known and predictable drawback of the fully covered design has been an increase in the rate of migration, ranging from 20% to 39% in most studies [8,9,13,17]. Lower rates of migration, in the order of 7–12%, have been reported with some new fully covered SEMS [7,12,21,22]. A new, fully covered stent (WallFlex® ; Boston Scientific, Natick, MA) has recently been developed with internal covering and a dog-bone shape design aimed at reducing recurrent dysphagia by preventing migration and tissue in and overgrowth. Data on the performance of this stent in the management of malignant dysphagia are very limited. The FC WallFlex® stent was recently evaluated in a small, singlecentre, prospective study of 48 patients with both benign and malignant dysphagia [7]. For malignant strictures it showed good improvement in the dysphagia scores with a recurrent dysphagia rate of only 15%, and low rates of migration (9%), bleeding (6%), and tissue overgrowth (3%). Confirmed fistula formation was observed in two patients (6%), with another two having deep ulcers,
probably owing to a high radial force of the stent [7]. Another recent, small, single-centre, prospective study evaluated the fully covered WallFlex® stent in 20 patients with various indications, such as perforations, strictures and fistulas, both benign and malignant [8]. An overall response rate of 55% was observed (67% for malignant diseases) with an overall migration rate of 29%. Our prospective, multicentre, non-randomized, open-label study was therefore performed to evaluate technical feasibility, clinical outcome, and complication rates of the placement of a new fully covered WallFlex® stent as palliative treatment in a cohort of 82 consecutive patients with dysphagia from inoperable primary oesophageal cancer. In this study, we demonstrate that the fully covered WallFlex® stent provides good relief of malignant dysphagia and is associated with low rates of migration and other complications. Similarly to previous reports for other stents in malignant strictures [9–20], stent placement in our cohort was safe and easy in almost all cases (98.8%), with only a minority of patients (18.2%) requiring pre-stent placement dilation. The fully covered WallFlex® stent provided a good relief of malignant dysphagia, reducing the score from a median of 3 to a median of 1 (P < 0.001) both at 14 days and 4 weeks after stent placement, in line with previous studies. Recurrent dysphagia was observed in 19 patients (23.1%) and was caused by stent migration (N = 10; 12.2%), tissue overgrowth (N = 7; 8.5%), or food impaction (N = 2; 2.4%). The overall dysphagia recurrence rate with SEMS, for any reason, ranges between 12% and 49% in the literature [10–18,23]. Even though our migration rate is slightly higher than a previous experience with the same fully covered WallFlex® stent, which found a recurrence rate of 15% [7], it falls neatly within the rates of recurrent dysphagia reported in the literature. More specifically, the migration rate observed in our study is comparable with the rates found in the most favourable experiences with other fully covered stent designs [7,12,19–22] and, more interestingly, is similar to the migration rates reported with the partially covered oesophageal SEMS [10,15–18,20–22]. A fact worth mentioning is that most of the stent migrations registered in our study (7 out of 10) occurred in patients with strictures located across the gastroesophageal junction, a location predisposing to stent migration, as data from the literature suggest [12,14,20–24]. These favourable migration rates are likely the result of the new design of the stent, i.e., internal covering and a doublefunnel shape that stabilizes it in the stricture [7–9,24]. As expected from the fully covered stent design, we did not observe any case of tissue ingrowth [13,20], whilst our rate of tissue overgrowth is comparable to the rates reported with fully covered SEMS or fully covered self expandable plastic stents, which range between 0% and 38% [12–14,18,22–24], and to previous experiences with the WallFlex® stent which ranged from 0% to 19% [7–9]. Four of these patients were successfully treated with either APC [12] or placement of a second stent [10,12], while one refused further treatment and the other was left untreated for critical clinical conditions. The low rate of food obstruction observed in our study (2.4%) is partly due to the presence of the internal covering of the WallFlex® stent, and partly to the careful dietary instructions given to our patients [20]. A total of four patients (7.6%) experienced major complications, including three (3.7%) late severe haemorrhage episodes and one late perforation. Two of the patients that experienced bleeding required blood transfusion, while the other died from massive haemorrhage, likely from an aorto-oesophageal fistula. In all three cases the largest stent type (23 mm × 28 mm × 125 mm) had been used. In a previous study, the larger diameter of the Gianturco Zstent was associated with higher rates of major complication when compared to stents with smaller diameter [23]. The small number of major complications recorded in our study does not allow us to determine if the association between these complications
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and a larger diameter is also true for the fully covered WallFlex® stent. Only supportive care was given to the patient who experienced perforation, in consideration of his will and poor clinical conditions, and he died shortly after. Therefore, we had two stentrelated deaths in our study (2.4%). Our rates of major complications are well within the range of those observed in other studies with both fully and partially covered SEMS, which ranged from 0 to 40%, and in particular bleeding, which ranged from 0% to 18%, and perforation/fistula formation, which ranged from 0% to 15% in the aforementioned studies. Therefore, the overall recurrent dysphagia and major complication rates with the new FC WallFlex® stent are in the lower-end of the spectrum of complication rates observed with other SEMS. In particular, the low migration rate of the fully covered WallFlex® stent compares very well not only with the migration rates of other fully covered SEMS, but also with the migration rates of the partially covered SEMS. Nearly one-third of our patients had received radiotherapy and/or chemotherapy prior or subsequent to stent placement. Data regarding the effect of prior radiochemotherapy on the risk of complications after SEMS placement are conflicting, with some reporting an increased risk [7,25], particularly for definitive radiochemotherapy [11], and others not finding any additional risk factor in these prior therapies [26]. A univariate analysis of our data found no association between the rate of complications and/or recurrence of dysphagia with either prior or subsequent radio and/or chemotherapy. Since complications from radiochemiotherapy are usually dose-dependent [11], these results probably reflect the lower palliative dose regimens of radio and/or chemotherapy administered to the patients included in our study. Our study has several strengths. First, differently from several previous studies, we included a strongly homogeneous population of patients, in terms of clinical indication and stent design. Second, this study includes the largest number of patients treated with the new fully covered WallFlex® stent, followed up for a relatively long time (>5 months) and with no patient lost to follow-up. Finally, its prospective and multicentre design allows for a better estimation of adverse events and a greater reproducibility of the results in the general clinical practice, as opposed to previous retrospective designs and single-centre experiences. Among the weaknesses of our study we recognize the non-randomized, open-label design and the lack of comparison with other treatment options. Future well-designed, randomized, controlled clinical trials will allow to better define the role of the new WallFlex® stent in comparison to other therapeutic/palliative strategies for the management of oesophageal cancer. Moreover, well-designed, homogeneous studies will be necessary to adequately assess the efficacy and safety of the fully covered WallFlex® stent in other oesophageal diseases as well. Such conditions may include benign dysphagia (such as post-surgical or post-radiotherapy oesophageal strictures) or else the presence of oesophago-tracheal fistula (both benign or malignant). In this last setting SEMS placement has proven to be an excellent treatment option [10,24]. In conclusion, our study demonstrates that the fully covered oesophageal WallFlex® stent is safe and effective for the palliation of dysphagia from inoperable primary oesophageal cancer strictures, with high technical and clinical success, as well as low complication and migration rates.
Conflict of interest Dr. A. Repici: serves as Consultant for Boston Scientific; Dr. P.D. Siersema: serves as Consultant for Boston Scientific. All other authors have no conflicts of interest or financial ties to disclose.
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Appendix A. Participating centres Humanitas Research Hospital, Rozzano, Milan, Italy Santa Chiara Hospital, Pisa, Italy Civic Hospital of Palermo, Palermo, Italy Cremona Hospital, Cremona, Italy Acireale Hospital, Acireale, Italy Camposampiero Hospital, Camposampiero, Italy S. Orsola-Malphigi Hospital, Bologna, Italy National Cancer Institute, G. Pascale Foundation, Naples, Italy University Medical Center Utrecht, Utrecht, Netherlands References [1] Parkin DM, Bray F, Ferlay J. Global cancer statistic 2002. CA: A Cancer Journal for Clinician 2005;55:74–108. [2] Pisani P, Parkin DM, Bray F, et al. Estimates of the worldwide mortality from 25 cancers in 1990. International Journal of Cancer 1999;83:18–29. [3] Stein Hj, Siewert JR. Improved prognosis of resected oesophageal cancer. World Journal of Surgery 2004;28:520–5. [4] Homs MY, Kuipers EJ, Siersema PD. Palliative therapy. Journal of Surgical Oncology 2005;92:246–56. [5] Siersema PD. Treatment options for oesophageal strictures. Nature Clinical Practice Gastroenterology & Hepatology 2008;5:142–52. [6] Repici A, Rando G. Expandable stent for malignant dysphagia. Techniques in Gastrointestinal Endoscopy 2008;10:175–83. [7] Hirdes MM, Siersema PD, Vleggaar FP. A new fully covered metal stent for the treatment of benign and malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2012;75:712–8. [8] Wagh MS, Forsmark CE, Chauhan S, et al. Efficacy and safety of a fully covered oesophageal stent: a prospective study. Gastrointestinal Endoscopy 2012;75:678–82. [9] Siddiqui AA, Sarkar A, Beltz S, et al. Placement of fully covered selfexpandable metal stents in patients with locally advanced oesophageal cancer before neoadjuvant therapy. Gastrointestinal Endoscopy 2012;76: 44–51. [10] van Heel NC, Haringsma J, Boot H, et al. Comparison of 2 expandable stents for malignant oesophageal disease: a randomized controlled trial. Gastrointestinal Endoscopy 2012;76:52–8. [11] Didden P, Spaander MC, Kuipers EJ, et al. Safety of stent placement in recurrent or persistent oesophageal cancer after definitive chemoradiotherapy: a case series. Gastrointestinal Endoscopy 2012;76:426–30. [12] Lazaraki G, Katsinelos P, Nakos A, et al. Malignant oesophageal dysphagia palliation using insertion of a covered Ultraflex stent without fluoroscopy: a prospective observational study. Surgical Endoscopy 2011;25: 628–35. [13] Uitdehaag MJ, Siersema PD, Spaander MC, et al. A new fully covered stent with antimigration properties for the palliation of malignant dysphagia: a prospective cohort study. Gastrointestinal Endoscopy 2010;71:600–5. [14] Uitdehaag MJ, van Hooft JE, Verschuur EM, et al. A fully-covered stent (AlimaxxE) for the palliation of malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2009;70:1082–9. [15] van Boeckel PG, Siersema PD, Sturgess R, et al. A new partially covered metal stent for palliation of malignant dysphagia: a prospective follow-up study. Gastrointestinal Endoscopy 2010;72:1269–73. [16] van Boeckel PG, Repici A, Vleggaar FP, et al. A new metal stent with a controlledrelease system for palliation of malignant dysphagia: a prospective, multicenter study. Gastrointestinal Endoscopy 2010;71:455–60. [17] Eloubeidi MA, Lopes TL. Novel removable internally fully covered selfexpanding metal oesophageal stent: feasibility, technique of removal, and tissue response in humans. American Journal of Gastroenterology 2009;104:1374–81. [18] Conio M, Repici A, Battaglia G, et al. A randomized prospective comparison of self-expandable plastic stents and partially covered self-expandable metal stents in the palliation of malignant oesophageal dysphagia. American Journal of Gastroenterology 2007;102:2667–77. [19] Conigliaro R, Battaglia G, Repici A, et al. Polyflex stent for malignant oesophageal and oesophagogastric stricture: a prospective, multicentric study. European Journal of Gastroenterology and Hepatology 2007;19:195–203. [20] Vleggaar FP, Siersema PD. Expandable stents for malignant oesophageal disease. Gastrointestinal Endoscopy Clinics of North America 2011;21:377–88, vii. [21] Verschuur EM, Homs MY, Steyerberg EW, et al. A new oesophageal stent design (Niti-S stent) for the prevention of migration: a prospective study in 42 patients. Gastrointestinal Endoscopy 2006;63:134–40. [22] Verschuur EM, Repici A, Kuipers EJ, et al. New design oesophageal stents for the palliation of dysphagia from oesophageal or gastric cancer cardia cancer: a randomized trial. American Journal of Gastroenterology 2008;103: 304–12. [23] Verschuur EM, Steyerberg EW, Kuipers EJ, et al. Effect of stent size on complications and recurrent dysphagia in patients with oesophageal or gastric cardia cancer. Gastrointestinal Endoscopy 2007;65:592–601.
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[24] Seven G, Irani S, Ross AS, et al. Partially versus fully covered selfexpanding metal stents for benign and malignant oesophageal conditions: a single center experience. Surgical Endoscopy 2013;27: 2185–92. [25] Lecleire S, Di Fiore F, Ben-Soussan E, et al. Prior chemoradiotherapy is associated with a higher life-threatening complication rate after palliative insertion of
metal stents in patients with oesophageal cancer. Alimentary Pharmacology and Therapeutics 2006;23:1693–702, 15;. [26] Homs MY, Hansen BE, van Blankenstein M, et al. Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma. European Journal of Gastroenterology and Hepatology 2004;16:163–70.