Clinical outcomes of self-expandable stent placement for benign esophageal diseases: A pooled analysis of the literature

Table 1 Literature on self-expandable stent placement for refractory benign esophageal strictures

Ref.	Study design	Patients, indications	Stent type, technical success rate, scheduled removal	Follow-up median (range)	Complications	Successful stent removal	Clinical success (dysphagia-free)
Prospective cohort studies including patients with RBES according to Kochman’s criteria
Chaput et al[9] 2013	Prospect	Patients with recurrent benign strictures after more than 3 dilatations to more than 15 mm during the previous 12 mo: n = 41 1 Anastomotic stricture: 29% (12/41) 2 Peptic stricture: 39% (16/41) 3 Caustic stricture: 7% (3/41) 4 Radiation stricture: 20% (8/41) 5 Others: 5% (2/41)	Standard FC SEMS: 100% (24/24) - 4 wk Multilayer silicone FC SEMS: 100% (17/17) - 3 mo	24 mo	Overall complications: Stent migration: 29.3% (12/41) Chest pain requiring stent removal or repositioning: 9.8% (4/41) Chest pain resolved with conservative management: 2.4% (1/41) Vomiting: 2.4% (1/41) Pneumonia: 2.4% (1/41)	FC SEMS: 100% (41/41)	Overall clinical success: 9.8% (4/41)
Canena et al[10] 2012	Prospect	Patients with RBES according to Kochman criteria: n = 30 1 Anastomotic stricture: 43% (13/30) 2 Peptic stricture: 23% (7/30) 3 Caustic stricture: 10% (3/10) 4 Radiation stricture: 7% (2/30) 5 Idiopathic stricture: 17% (5/30)	BD stent: 100% (10/10) SEPS: 100% (10/10) - 12 wk FC SEMS: 100% (10/10) - 12 wk	23.4 (8-66) mo	Patients with complications (P = 0.38): BD stent 50%, SEPS 70%, FC SEMS 60% Stent migration (P = 0.16): BD stent 20%, SEPS 60%, FC SEMS 30% Tissue hyperplasia (P = 0.09): BD stent 30%, SEPS 0%, FC SEMS 0% Associated with one major bleeding and recurrent dysphagia in two patients Minor complications in 17% (5/30) of patients: 1 Globus sensation: BD stent 0%, SEPS 0%, FC SEMS 10% 2 Moderate chest pain: BD stent 0%, SEPS 20%, FC SEMS 10% 3 Reflux: BD stent 0%, SEPS 10%, FC SEMS 10% Major complications in 7% (2/30) of patients: 1 Major bleeding: BD stent 10%, SEPS 0%, FC SEMS 0% 2 Severe chest pain: BD stent 10%, SEPS 0%, FC SEMS 0%	SEPS: 100% (10/10) FC SEMS: 100% (10/10)	Overall: 27% (8/30) Stent type (P = 0.27): 1 BD stent: 30% (3/10) 2 SEPS: 10% (1/10) 3 FC SEMS: 40% (4/10)
Hirdes et al[11] 2012	Prospect	Patients with RBES according to Kochman criteria: n = 28 1 Peptic stricture: 32% (9/28) 2 Anastomotic stricture: 25% (7/28) 3 Radiation stricture: 11% (3/28) 4 Caustic stricture: 7% (2/28) 5 Others: 11% (3/28) 6 Unknown origin: 14% (4/28)	Single BD stent: n = 15 Sequential BD stent: n = 13 Technical success: 100% (28/28) In total 59 BD stent placed	630 (21-1121) d	Stent migration: 10.7% (3/28) Food impaction: 10.7% (3/28) Major complications of 59 stent placements in 28 patients: 29% (8/28) of patients 1 Retrosternal pain and vomiting: 7.1% (2/28) 2 Retrosternal pain: 7.1% (2/28) 3 Bleeding: 7.1% (2/28) 4 Fever and vomiting: 3.6% (1/28) 5 Aspiration pneumonia: 3.6% (1/28) Minor complications of 59 stent placements in 28 patients: 14% (4/28) of patients 1 Retrosternal pain: 7.1% (2/28) 2 Reflux: 3.6% (1/28) 3 Vomiting: 3.6% (1/28) One patient (3.6%) died of aspiration pneumonia, relation to stent unclear	Not applicable	At 6 mo after: First stent: 25% (7/28) Second stent: 15% (2/13) Third stent: 0% (0/7)
Hirdes et al[12] 2012	Prospect	Patients with RBES according to Kochman criteria: n = 15 1 Peptic stricture: 40% (6/15) 2 Caustic stricture: 20% (3/15) 3 Radiation stricture: 13% (2/15) 4 Other: 7% (1/15) 5 Unknown cause: 20% (3/15)	FC SEMS: 100% (15/15) 109 d (87-222)	After stent removal: 86 (14-330) d	Stent migration: 33% (5/15) Tissue overgrowth: 20% (3/15) Major complications in 20% (3/15) of patients: 1 Severe pain requiring stent removal: 7% (1/15) 2 Severe persistent odynophagia: 7% (1/15) 3 Nausea/vomiting: 13% (2/15) 4 Aspiration pneumonia: 7% (1/15) Minor complications: 1 Pain: 20% (3/15)	93% (14/15) Stent-in-stent: 7%	0% (0/15)
Eloubeidi et al[13] 2011	Pro- and retrospect	Patients with benign esophageal lesions treated with Alimaxx-E stent: n = 35 Leaks/fistulae: n = 12 Perforations: n = 4 RBES: n = 19 1 Anastomotic stricture: 37% (7/19) 2 Peptic stricture: 21% (4/19) 3 Caustic stricture: 11% (2/19) 4 Radiation stricture: 11% (2/19) 5 Others: 21% (4/19)	FC SEMS: 100% (19/19) In situ for: 64 ± 74 d (range 6-300)	161 ± 111 (range 24-360) d	Stent migration: 36.8% (7/19) Minor complications in patients with RBES: 1 Stent infolding/invagination: 16% (3/19) 2 Chest pain: 5% (1/19) 3 Abdominal pain: 11% (2/19) 4 Globus sensation: 5% (1/19) 5 Fever: 5% (1/19) Major complications in patients with RBES: 1 Arrhythmia: 5% (1/19)	97% (34/35) Stent fracture: 3%	21% (4/19)
Van Boeckel et al[14] 2011	Prospect	Patients with RBES according to Kochman criteria: n = 38 1 Anastomotic stricture: 34% (13/38) 2 Peptic stricture: 18% (7/38) 3 Radiation stricture: 18% (7/38) 4 Caustic stricture: 16% (6/38) 5 Others: 11% (4/38) 6 Unknown etiology: 3% (1/38)	BD stent: 100% (18/18) SEPS: 95% (19/20) - 6 wk	BD stent: 166 (21-559) d SEPS: 385 (77-924) d	Major complications: 15.8% (6/38) 1 Hemorrhage: SEPS 5%, BD stent 11% 2 Perforation: SEPS 5%, BD stent 0% 3 Severe pain requiring opiates: SEPS 0%, BD stent 11% Minor complications: 10.5% (4/38) 1 Reflux: SEPS 0%, BD stent 6% 2 Nausea/vomiting: SEPS 5%, BD stent 11% Stent migration: SEPS 25% (5/20), BD stent 22% (4/18) Food impaction: SEPS 0%, BD stent 11% (2/18) Tissue in-/overgrowth: SEPS 0%, BD stent 11% (2/18) A FC SEMS was placed in both patients	SEPS: 100% (16/16)	Stent type (P = 0.83): 1 SEPS: 30% (6/20) 2 BD stent: 33% (6/18)
Repici et al[15] 2010	Prospect	Patients with RBES according to Kochman criteria: n = 21 1 Peptic stricture: 33% (7/21) 2 Anastomotic stricture: 24% (5/21) 3 Radiation stricture: 24% (5/21) 4 Caustic stricture: 10% (2/21) 5 Other: 5% (1/21) 6 Idiopathic stricture: 5% (1/21)	BD stent: 100% (21/21)	53 (25-88) wk	Stent migration: 9.5% (2/21) Severe thoracic pain requiring analgesics: 14.3% (3/21) Minor bleeding: 4.8% (1/21) Dysphagia caused by hyperplastic tissue: 4.8% (1/21)	Not applicable	45% (9/20)
Dua et al[16] 2008	Prospect	Patients with RBES according to Kochman criteria: n = 40 1 Anastomotic stricture: 30% (12/40) 2 Caustic stricture: 20% (8/40) 3 Radiation stricture: 18% (7/40) 4 Peptic stricture: 5% (2/40) 5 Others: 28% (11/40)	SEPS: 95% (38/40) 4 wk	53 (11-156) wk	Stent migration: 22.2% (8/36) Severe chest pain requiring medication: 11.1% (4/36) Fistula: 2.8% (1/36) Perforation: 5.6% (2/36) Gastroesophageal reflux: 5.6% (2/36) Bleeding: 8.3% (3/36) Stent-related mortality: 2.8% (1/36) Massive bleeding probably due to stent eroding into major vessel	94% (31/33) Inability to remove stent: 6% (2/33)	30% (12/40)
Remaining prospective cohort studies
Van Hooft et al[17] 2011	Prospect	Patients with an esophagogastric anastomotic stricture who did not have had any endoscopic treatment: n = 10	BD stent: 100% (10/10)	6 mo	Food impaction: 10% (1/10) Hyperplasia-induced obstruction: 20% (2/10)	Not applicable	60% (6/10)
Evrard et al[18] 2004	Prospect	SEMS-induced stricture: n = 5 Esophagocolonic anastomotic stricture: n = 4 Refractory benign strictures after a median of 6 (range 1-12) dilation sessions per year: n = 8 Anastomotic leak: n = 4	SEPS: 100% (21/21) Range 2 d–18 mo	After stent removal: 21 (8-39) mo	Stent migration: 57.1% (12/21) Stridor due to tracheal compression: 4.8% (1/21) Inflammatory epiglottic stenosis: 4.8% (1/21)	100% (21/21)	76% (13/17)
Repici et al[19] 2004	Prospect	Patients with persisting benign esophageal strictures after at least 6 dilation sessions: n = 15 1 Caustic stricture: 33% 2 Anastomotic stricture: 27% 3 Radiation stricture: 27%	SEPS: 100% (15/15) 6 wk	Mean: 22.7 (19-27) mo	Severe chest pain requiring analgesics: 33% (5/15) Mild/moderate mucosal hyperproliferation: 27% (4/15) Stent migration: 7% (1/15)	100% (15/15)	80% (12/15)

RBES: Refractory benign esophageal strictures; SEPS: Self-expandable plastic stent; BD stent: Biodegradable stent; FC SEMS: Fully covered self-expandable metal stent.

Table 2 Pooled analysis of 232 patients with refractory benign esophageal strictures according to Kochman’s criteria treated with self-expandable stent placement n (%)

Stricture etiology
Anastomotic strictures	69 (29.7)
Peptic strictures	58 (25.0)
Radiation strictures	36 (15.5)
Caustic strictures	29 (12.5)
Others	26 (11.2)
Unknown	14 (6.0)
Stent type
FC SEMS	85 (36.6)
BD stent	77 (33.2)
SEPS	70 (30.2)
PC SEMS	0 (0)
Technical success
Overall	229 (98.7)
FC SEMS	85 (100)
BD stent	77 (100)
SEPS	67 (95.7)
Clinical success
Overall (n = 231)	56 (24.2)
FC SEMS (n = 85)	12 (14.1)
BD stent (n = 76)	25 (32.9)
SEPS (n = 70)	19 (27.1)

FC SEMS: Fully covered self-expandable metal stent; BD stent: Biodegradable stent; SEPS: Self-expandable plastic stent; PC SEMS: Partially covered self-expandable metal stent.

Table 3 Pooled analysis of adverse events in patients with refractory benign esophageal strictures n (%)

Overall complications	72 (31.0)
Overall major complications	41 (17.7)
FC SEMS (n = 85)	9 (10.6)1
Severe retrosternal pain	5 (5.9)
Severe nausea and vomiting	2 (2.4)
Aspiration pneumonia	2 (2.4)
Arrhythmia	1 (1.2)
Percutaneous endoscopic gastrostomy because of impaired intake caused by severe, persistent odynophagia	1 (1.2)
BD stents (n = 77)	22 (28.6)1
Severe retrosternal pain	10 (13.0)
Hyperplasia-induced stenosis	5 (6.5)
Bleeding, hematemesis	5 (6.5)
Severe nausea and vomiting	3 (3.9)
Aspiration pneumonia	1 (1.3)
SEPS (n = 70)	10 (14.3)
Severe retrosternal pain	4 (5.7)
Perforation	3 (4.3)
Bleeding, hematemesis2	2 (2.9)
Stent-induced fistula	1 (1.4)
Overall minor complications	31 (13.4)
FC SEMS (n = 85)	15 (17.6)1
Retrosternal pain	6 (7.1)
Stent infolding/invagination	3 (3.5)
Abdominal pain	2 (2.4)
Globus sensation	2 (2.4)
Reflux symptoms	1 (1.2)
Vomiting	1 (1.2)
Fever	1 (1.2)
BD stents (n = 77)	8 (10.4)
Nausea and vomiting	3 (3.9)
Retrosternal pain	2 (2.6)
Reflux symptoms	2 (2.6)
Minor bleeding	1 (1.3)
SEPS (n = 70)	8 (11.4)
Reflux symptoms	3 (4.3)
Retrosternal pain	2 (2.9)
Minor bleeding	2 (2.9)
Nausea and vomiting	1 (1.4)

¹Patients can have more than one complication;

²Including one stent-related death from massive bleeding. FC SEMS: Fully covered self-expandable metal stent; BD stent: Biodegradable stent; SEPS: Self-expandable plastic stent; PC SEMS: Partially covered self-expandable metal stent.

Table 4 Literature on self-expandable stent placement for benign esophageal leaks, perforations and fistulae

Ref.	Study design	Patients	Stent type, technical success (%) and time to removal	Additional sepsis-related procedures, follow-up	Complications and mortality	Successfulstent removal	Clinical success
Dua et al[29] 2014	Pro- and retrospect	Patients treated with a non-foreshortening FC SEMS for benign esophageal leaks: n = 6 1 Postsurgical leaks: n = 5 2 Esophagopericardial fistula: n = 1 Single stent: 83% (5/6) Multiple stents: 17% (1/6)	FC SEMS: 100% (7/7) Median time to removal: 50 (49-56) d	Unknown FU: unknown	Minor complications: Pneumoperitoneum during endoscopy secondary to air insufflation: 17% (1/6) Stent migration: 17% (1/7) Mortality rate: 33.3% (2/6) - cerebral embolism: 16.7% (1/6) - sepsis-related: 16.7% (1/6)	FC SEMS: 100% (4/4)	Overall: 67% (4/6) -Postsurgical leaks: 80% (4/5) -Fistula: 0% (0/1)
El Hajj et al[30] 2014	Retrospect	Patients with attempted stent placement for esophageal leaks, fistulae and perforations: 1 Postsurgical leaks: n = 29 Single stent: 72% (21/29) Multiple stents: 28% (8/29) Excluded from analysis because patients were included with active malignancy: 1 Perforations: n = 10 2 Fistulae: n = 15	PC SEMS: 100% (19/19) - 4 to 6 wk FC SEMS: 100% (30/30) - 6 to 8 wk SEPS: 100% (15/15) - 6 to 8 wk	Not analyzed for subgroup of patients with anastomotic leaks ≥ 3 mo FU: 100%	No subgroup analysis for patients with esophageal leaks 1 Chest pain 2 GI Bleed 3 Pneumothorax 4 Increase size of leak during deployment 5 Breakage of stent 6 Dysphagia 7 Aspiration pneumonia Stent migration not analyzed for subgroup of patients with esophageal leaks Mortality rate: 0% (0/29)	No subgroup analysis for patients with postsurgical leaks -Stent-in-stent procedure: 2 -Breakage of stent: 1	Overall: 82.8% (24/29) -Primary closure rate: 72% (21/29) -Secondary closure rate: 38% (3/8)
Freeman et al[31] 2014	Retrospect	Patients with intrathoracic leak after surgical repair of an acute iatrogenic esophageal perforation: n = 29 Single stent: 100% (29/29)	SEPS: 100% (24/24) FC SEMS: 100% (5/5) Mean time to removal: 22 (13-41) d	PEG: 10.3% (3/29) Thoracoscopic decortication: 10.3% (3/29) Jejunostomy: 3.4% (1/29) Median FU: 6 wk	No stent-related complications. Stent migration: 17.2% (5/29) - not analyzed according to stent type Mortality rate: 0% (0/29)	100% (25/25) Not analyzed according to stent type	86.2% (25/29)
Gubler et al[32] 2014	Retrospect	Patients with benign (gastro)esophageal leaks, fistulae or perforations: n = 85 1 Iatrogenic perforations: n = 32 2 Anastomotic leaks: n = 31 3 Fistulae: n = 7 4 Boerhaave: n = 7 5 Other perforations: n = 8 Single stent: 78% (66/85) Multiple stents: 22% (19/85)	Total SEMS: n = 113 PC SEMS: n = 72 FC SEMS: n = 28 Unknown: n = 13 Technical success: 100% Average time to removal: 15 (1-111) d	Percutaneous/thoracoscopic drainage: 55.3% (47/85) OTSC: 2.4% (2/85) Vacuum-therapy: 2.4% (2/85) FU: at least 4 wk after stent removal	Stent migration: 8.8% (10/113) - not analyzed according to stent type Food bolus obstruction: 0.9% (1/113) - not analyzed according to stent type Mortality rate: 9.4% (8/85) 1 Unrelated to in situ stent: 3.5% (3/85) 2 Multi-organ failure: 2.4% (2/85) 3 Acute respiratory distress syndrome: 1.2% (1/85) 4 Heart insufficiency: 1.2% (1/85) 5 Aortic dissection: 1.2% (1/85)	98.2% (107/109) - Irremovable: 2 - Spontaneous passage after migration: 1 Not analyzed according to stent type	Overall: 79% (67/85) -Postsurgical leaks: 74% (23/31) -Fistulae: 43% (3/7) -Iatrogenic: 94% (30/32) -Boerhaave: 71% (5/7) -Others: 75% (6/8) PC SEMS: 68% (49/72) FC SEMS: 54% (15/28)
Orive-Calzada et al[33] 2014	Pro- and retrospect	Patients treated with FC SEMS for benign upper gastrointestinal fistulae and perforations: n = 56 1 Postsurgical leaks: n = 44 2 Iatrogenic perforations: n = 6 3 Boerhaave syndrome: n = 4 4 Other perforations: n = 2 Single stent: 59% (33/56) Multiple stents: 41% (23/56)	FC SEMS: 100% (87/87) PC SEMS: 100% (1/1) Median time to removal: 42 (9-1460) d	Surgical drainage: 30% (17/56) Percutaneous drainage: 41% (23/56) FU: unknown	Minor complications: Atrial fibrillation: 1.8% (1/56) Major complications: Stent-related perforation: 5.4% (3/56) Stent migration: 20.5% (18/88) - FC SEMS: 20.7 (18/87) - PC SEMS: 0% (0/1) Mortality rate: 16% (9/56) - cerebrovascular accident: 1.8% (1/56) - nosocomial pneumonia: 1.8% (1/56) - neoplasia: 1.8% (1/56) - secondary to sepsis: 10.7% (6/56)	FC SEMS: 100% (87/87) PC SEMS: 0/1 -Stent-in-stent procedure: 1	Overall: 79% (44/56) -Postsurgical leaks: 78% (36/46) -Perforations: 80% (8/10)
Persson et al[34] 2014	Retrospect	Patients with benign spontaneous, iatrogenic or traumatic esophageal perforations: n = 40 1 Iatrogenic perforation: n = 16 2 Boerhaave syndrome: n = 23 3 Other perforations: n = 1 Single stent: missing Multiple stents: missing	Total No. of stents missing Stent type missing Time to removal: 4-6 wk	Unknown FU: unknown	No stent-related complications Stent migration not analyzed according to stent type Mortality rate: 7.5% (3/40) 1 Multi-organ failure: 5% (2/40) 2 Respiratory insufficiency without sepsis: 2.5% (1/40)	Stent type and no. of stents removed missing -Removal during second procedure: 1	82.5% (33/40) No subgroup analysis according to etiology
Sharaiha et al[35] 2014	Retrospect	Patients treated with stent placement for benign upper GI leaks: n = 18 1 Postsurgical leaks: n = 12 2 Iatrogenic perforation: n = 1 3Other fistulae: n = 5 Single stent: 28% (5/18) Multiple stents: 72% (13/18)	Total stents: n = 47 1 FC SEMS 2 PC SEMS 3 SEPS 4 Uncovered Technical success: 100% Mean time to removal: 54 (18-118) d	Clip/endoloop: 27.8% (5/18) Dilation: 33.3% (6/18) Surgery: 16.7% (3/18) FU: median 283 d (IQR 38-762)	Overall 9 complications in 5 patients 5 minor complications in 4 patients: - reflux/esophagitis: 16.7% (3/18) - abdominal pain: 5.6% (1/18) - collapsed stent: 5.6% (1/18) 4 Major complications in 3 patients: - aspiration pneumonia: 11.1% (2/18) - perforation: 5.6% (1/18) - stricture: 5.6% (1/18) Tissue hyperplasia: 5.6% (1/47) - stent type unknown Food impaction/bezoar: 11.1% (2/47) - stent type unknown Stent migration not analyzed for subgroup of patients with esophageal leaks Overall mortality rate: 5.6% (1/18) Not specified	No subgroup analysis for patients with benign leaks -Stent-in-stent procedure: 7 -Irremovable uncovered stent: 1	Overall: 47% (7/15) -Postsurgical leaks: (5/11) -Fistula: 67% (2/3) -Iatrogenic: 0% (0/1)
Shim et al[36] 2014	Retrospect	Patients who underwent endoscopic treatment for anastomotic leakage after total gastrectomy: n = 27 1 FC SEMS: n = 13 2 Non stent therapy: n = 14 Single stent: 85% (11/13) Multiple stents: 15% (2/13)	FC SEMS: 100% (15/15) PC SEMS: 100% (1/1) Median time to removal: 38 (0-69) d	Concurrent fluid drainage: 61.5% (8/13) FU: unknown	Minor complication: Stent malposition: 6.3% (1/13) Stent migration: 25% (4/16) - FC SEMS: 26.7% (4/15) - PC SEMS: 0% (0/1) Tissue in- or overgrowth: 6.3% (1/16) - FC SEMS: 6.7% (1/15) Mortality rate: 15.4% (2/13) - sepsis related: 7.7% (1/13) - non-stent related bleeding: 7.7% (1/13)	FC SEMS: 100% (11/11) PC SEMS: 100% (1/1)	Overall: 67% (8/12) -Primary closure rate: 67% (8/12) -Secondary closure rate: 0% (0/4)
Brangewitz et al[37] 2013	Retrospect	Patients with esophageal defects treated with stent placement: n = 39 1 Postsurgical leaks: n = 31 2 Iatrogenic perforations: n = 6 3 Boerhaave syndrome: n = 2 Single stent: 100% (39/39)	FC SEMS: 100% (39/39) Median time to removal: 33 (9-132) d	Unknown FU: unknown	Minor complications: - stent-related ulcers: 12.8% (5/39) Major complications: - severe bleed at upper end of stent: 2.6% (1/39) - death due to esophageal necrosis at proximal end of stent: 2.6% (1/39) Stent migration: 15.4% (6/39) Mortality rate: 25.6% (10/39) - esophageal necrosis at proximal stent end: 2.6% (1/39) - not specified: 23.1% (9/39)	FC SEMS: 90.3% (28/31) -Self-limiting bleed: 2 -Migrated stent requiring surgical removal: 1	53.8% (21/39) No subgroup analysis according to etiology
Leenders et al[38] 2013	Retrospect	Patients with anastomotic leakage after esophageal resection or bariatric surgery: n = 26 Single stent: 81% (21/26) Multiple stents: 19% (5/26)	FC SEMS: 100% (31/31) PC SEMS: 100% (2/2) Mean time to removal: 11 (1-63) wk	Unknown FU: range 2-144 wk	Minor complications: - stent disintegration all with FC SEMS: 11.5% (3/26) Major complications: - stent-related perforation with FC SEMS: 3.8% (1/26) Stent migration: 24.2% (8/33) - FC SEMS: 25.8% (8/31) Tissue ingrowth: 6.1% (2/33) - PC SEMS: 100% (2/2) Mortality rate: 19.2% (5/26) - sepsis-related: 19.2% (5/26)	FC SEMS: 100% (26/26) PC SEMS: 0% (0/2) -Traumatic removal due to tissue ingrowth: 2	80.8% (21/26)
Wilson et al[39] 2013	Retrospect	Patients treated with FC SEMS placement for benign esophagogastric diseases: n = 33 1 Perforation: n = 7 2 Anastomotic leak: n = 14 3 Sleeve gastrectomy leak: n = 6 4 Fistula: n = 6 Single stent: missing Multiple stents: missing	FC SEMS: 100% (40/40) Average time to removal: 47 d	Drainage procedure: 66.7% (22/33) VATS/open: 36.4% (12/33) Tube thoracostomy: 21.2% (7/33) Percutaneous: 9.1% (3/33) FU: unknown	Major complications: - severe hemorrhage from aorta-esophageal fistula: 3.0% (1/33) No subgroup analysis for patients with esophageal leaks, fistulae and perforations: - stent migration - food impaction Mortality rate: 0% (0/33)	No subgroup analysis for patients with esophageal leaks, fistulae and perforations -Stent fracture: 2	94% (31/33) avoided open repair -Postsurgical leaks: 95% (19/20) -Perforations: 86% (6/7) -Fistulae: 100% (6/6)
Van Boeckel et al[40] 2012	Retrospect	Patients treated with a SEMS or SEPS for sealing a benign esophageal rupture or anastomotic leak: n = 52 1 Anastomotic leak: n = 32 2 Iatrogenic perforation: n = 13 3 Boerhaave syndrome: n = 4 4 Others: n = 3 Single stent: missing Multiple stents: missing	PC SEMS: 98% (60/61) FC SEMS: 100% (15/15) SEPS: 100% (7/7) Median time to removal: 25 (1-197) d	Concurrent fluid drainage: 46.2% (24/52) Median FU: 470 (25-1200) d	Major complications: Severe retrosternal pain: 3.8% (2/52) - all PC SEMS Hemorrhage: 3.8% (2/52) - FC SEMS: stent-related death 1.9% (1/52) - PC SEMS: required adrenaline injections: 1.9% (1/52) Ruptured stent cover: 7.2% (6/83) - PC SEMS: 9.8% (6/61) Tissue in-/overgrowth: 9.6% (8/83) - PC SEMS: 13.1% (8/61) Stent migration: 12.0% (10/83) - FC SEMS: 20% (3/15) - PC SEMS: 10% (6/61)	88.7% (63/71) Tissue in- and/or overgrowth at removal of 8 PC SEMS -Stent-in-stent procedure: 4 -Esophageal rupture: 2 -Second endoscopic procedure: 1 -Esophagectomy: 1 Not analyzed according to stent type	65.4% (34/52) No subgroup analysis according to etiology PC SEMS: 69% FC SEMS: 56% SEPS: 71%
					- SEPS: 14% (1/7) Food obstruction: 3.6% (3/83) - PC SEMS: 4.9% (3/61) Mortality rate: 13.5% (7/52) - severe stent-related hemorrhage: 1.9% (1/52) - sepsis related: 7.7% (4/52) - malignancy: 1.9% (1/52) - active euthanasia: 1.9% (1/52)
Buscaglia et al[41] 2011	Retrospect	Patients treated for benign esophageal conditions by FC SEMS placement: - fistula or leak: n = 15 Single stent: 67% (10/15) Multiple stents: 33% (5/15)	FC SEMS: 100% (24/24) Median time to removal: 42.5 (3-122) d	Unknown FU: unknown	Stent migration: 33.3% (8/24) Further complications not analyzed for subgroup of patients with fistulae and leaks - chest pain - globus sensation Mortality rate: 6.7% (1/15) - paraspinal abscess related to persistent fistula	No subgroup analysis for patients with esophageal leaks and fistulae -Removal during surgery: 1 -Stent-in-stent procedure: 1	79% (11/14) No subgroup analysis according to etiology
Dai et al[42] 2011	Retrospect	Patients treated with SEPS for: - postoperative esophageal anastomotic leaks: n = 30 Single stent: missing Multiple stents: missing Excluded from analysis because patients were included with active malignancy: - esophageal perforations: n = 6 - fistulae: n = 5	Total no. of SEPS missing Technical success: 100% Mean time to stent removal: 30 (7-62) d	Interventional drainage: 40% (12/30) Tracheotomy: 43% (13/30) Mean FU: 12.8 (1-61) mo	Major complications: - stent dislocation and inability to place new stent requiring rethoracotomy: 3.3% (1/30) Stent migration not analyzed for subgroup of patients with esophageal leaks Mortality rate: (2/30) - persistent sepsis and multi-organ failure: 6.7% (2/30)	No. of removed stents missing One migrated stent in a patient with an esophago-colonic anastomotic leak could not be removed	90% (27/30)
David et al[43] 2011	Pro- and retrospect	Patients treated with SEMS for esophageal or gastric perforation and intrathoracic contamination: n = 30 - postsurgical leak: n = 13 - boerhaave syndrome: n = 6 - iatrogenic perforation: n = 6 - fistulae: n = 4 - other perforation: n = 1 Single stent: 50% (15/30) Multiple stents: 50% (15/30)	At least 62 stents - FC SEMS - PC SEMS Technical success: 100% Average duration of stenting: 29 d	Chest tube thoracostomy: - Alone: 23.3% (7/30) - Additional intervention: 76.7% (23/30) Pleural decortication: 56.7% (17/30) Muscle-flap reinforcement: 36.7% (11/30) Average FU: 8.1 mo	Minor complications: - pain: 6.7% (2/30) - hiccups: 3.3% (1/30) - nausea: 3.3% (1/30) Major complications: - bowel obstruction: 6.7% (2/30) - erosion: 3.3% (1/30) - left atrial compression: 3.3% (1/30) Stent migration: 6.7% (2/30) - not analyzed according to stent type Mortality rate: 10% (3/30) - multi-organ failure: 3.3% (1/30) - multiple emboli caused by esophago-atrial fistula: 3.3% (1/30) - aspiration during contrast study: 3.3% (1/30)	No. of removed stents missing Not analyzed according to stent type	76.7% (23/30) No subgroup analysis according to etiology
Eloubeidi et al[13] 2011	Pro- and retrospect	Patients with benign esophageal lesions treated with Alimaxx-E stent: n = 16 - postsurgical leaks: n = 11 - fistula: n = 1 - iatrogenic perforations: n = 3 - other: n = 1 Single stent: 81% (13/16) Multiple stents: 19% (3/16)	FC SEMS: 100% (16/16) In situ for: 51 ± 45 d (range 9-163)	Dilation: 6.3% (1/16) PEG placement: 6.3% (1/16) FU: unknown	Minor complications: 1 Stent infolding/invagination: 6.3% (1/16) 2 Chest pain: 6.3% (1/16) 3 Dysphagia: 6.3% (1/16) 4 Globus sensation: 6.3% (1/16) Major complications: 1 Respiratory compromise: 6.3% (1/16) 2 Aspiration pneumonia: 12.5% (2/16) Stent migration: 31.3% (5/16) Mortality rate: 0% (0/16)	FC SEMS: 100% (16/16) One stent was retrieved in two pieces	43.8% (7/16) No subgroup analysis according to etiology
Freeman et al[44] 2011	Unknown	Hospitalized patients with an anastomotic leak after esophagectomy: n = 17 Single stent: 100% (17/17)	SEPS: 100% (14/14) FC SEMS: 100% (3/3) Mean time to removal: 17 (12-27) d	VATS pleural drainage: 29.4% (5/17) Pharyngostomy: 5.9% (1/17) Tube jenunostomy: 5.9% (1/17) FU: at least 3 mo after stent removal	No complications associated with stent placement or removal Stent migration: 17.6% (3/17) - not analyzed according to stent type Mortality rate: 0% (0/17)	SEPS: 100% (14/14) FC SEMS: 100% (3/3)	94% (16/17)
Nguyen et al[45] 2011	Retrospect	Patients who developed postoperative leaks after minimally invasive esophagectomy: n = 18 - conventional treatment: n = 9 - FC SEMS placement: n = 9 Single stent: 100% (9/9)	FC SEMS: 100% (9/9) Removal after 6 wk	Percutaneous drainage: 22% (2/9) Tracheostomy: 11% (1/9) FU: unknown	No stent-related complications Mortality rate: 0% (0/9)	FC SEMS: 100% (9/9)	100% (9/9)
Schweigert et al[46] 2011	Retrospect	Patients treated with stent placement for intrathoracic leak after esophagectomy: n = 12 Single stent: 100% (12/12)	PC SEMS: 100% (12/12) Median time to removal: 48 (16-99) d	Tube thoracostomy: 100% (12/12) FU: unknown	Major complications: 1 Death by hemorrhage from stent-related erosion into the aorta: 8.3% (1/12) 2 Stent-related fistula after removal: 8.3% (1/12) Stent migration: n = missing Mucosal hyperproliferation: n = missing Mortality rate: 16.7% (2/12) 1 Stent-related death by hemorrhage: 8.3% (1/12) 2 Pulmonary aspiration after stent removal and successful healing of the leak: 8.3% (1/12)	PC SEMS: 100% (10/10)	81.8% (9/11)
Swinnen et al[47] 2011	Retrospect	Patient treated with PC SEMS placement for benign upper GI leaks or perforations: n = 88 - postsurgical leaks: n = 65 - boerhaave syndrome: n = 4 - iatrogenic perforation: n = 14 - other perforations: n = 5	PC SEMS: 100% (153/153) Median time to removal for 33 PC SEMS: 23 d Median time to removal for 99 PC SEMS: 69 d	Drainage of collections: 47.7% (42/88) - Surgical: 26.1% (23/88) - Percutaneous: 15.9% (14/88) - Endoscopic: 5.7% (5/88)	Minor complications: - transient stent-related dysphagia: 11.4% (10/88) Major complications: - bleeding requiring intervention: 5.7% (5/88) - stent-related perforation: 1.1% (1/88)	PC SEMS: 24.4% (33/135) Stent-in-stent procedure: 73.3% (99/135) Removal during surgery: 2.2% (3/135)	77.6% (59/76) No subgroup analysis according to etiology
		Single stent: 58% (51/88) Multiple stents: 42% (37/88)		Follow-up after removal: 3 mo: 83% 7 mo: 81% 1 yr: 72%	- tracheal compression: 1.1% (1/88) - dysphagia due to tissue hyperplasia: 18.2% (16/88); PC SEMS: 10.5% (16/153) Stent migration: 11.1% (17/153) of PC SEMS mortality rate: 10.2% (9/88) 1 Sepsis related: 3.4% (3/88) 2 Pulmonary embolism: 1.1% (1/88) 3 Full-blown AIDS: 1.1% (1/88) 4 Cardiac disease: 1.1% (1/88) Three additional deaths during first 3 mo after treatment: 1 Sepsis after surgery: 1.1% (1/88) 2 Tension pneumothorax: 1.1% (1/88) 3 Pneumonia: 1.1% (1/88)

FC SEMS: Fully covered self-expandable metal stent; FU: Follow-up; PC SEMS: Partially covered self-expandable metal stent; SEPS: Self-expandable plastic stent; VATS: Video-assisted thoracic surgery; PEG: Percutaneous endoscopic gastrostomy; OTSC: Over-the-scope-clips; IQR: Interquartile range.

Table 5 Pooled analysis of 643 patients with benign esophageal leaks, perforations and fistulae treated with self-expandable stent placement

Etiology
Postsurgical leaks	415 (64.5)
Iatrogenic perforations	126 (19.6)
Boerhaave’s syndrome	50 (7.8)
Fistulae	24 (3.7)
Others/not specified	28 (4.4)
Stent type of 852 stents used in 573 patients1
FC SEMS	349 (41.0)
PC SEMS	321 (37.7)
SEPS	60 (7.0)
Stent type unknown	122 (14.3)
Technical success
Overall	851 (99.9)
FC SEMS	349 (100)
PC SEMS	320 (99.7)
SEPS	60 (100)
Stent type unknown	122 (100)
No. of stents per patient
Single stent placement	357 (55.5)
Multiple stents inserted	131 (20.4)
Unknown	155 (24.1)
Clinical success
Overall (n = 625)	480 (76.8)
According to etiology (n = 358)
Postsurgical leaks (n = 247)	201 (81.4)
Perforations2 (n = 86)	74 (86.0)
Fistulae (n = 17)	11 (64.7)
Others/not specified (n = 8)	6 (75.0)

¹In two studies including 70 patients the total number of stents used was not reported;

²Including iatrogenic and spontaneous perforations. FC SEMS: Fully covered self-expandable metal stent; PC SEMS: Partially covered self-expandable metal stent; SEPS: Self-expandable plastic stent.

Table 6 Pooled analysis of adverse events in patients with benign esophageal leaks, perforations and fistulae

Total number of patients analyzed: n = 599	No. of patients (n = 599)	No. of FC SEMS (n = 295)	No. of PC SEMS (n = 302)	No. of SEPS (n = 75)1	Stent type unknown (n = 162)2
Overall complications	803 (13.4)	26 (8.8)	38 (12.6)	1 (1.3)	17 (10.5)
Overall major complications	473 (7.8)	11 (3.7)	28 (9.3)	1 (1.3)	8 (4.9)
Hyperplasia-induced stenosis	16 (2.7)	0	16	0	0
Hemorrhage4	8 (1.3)	24	6	0	0
Stent-related perforation	6 (1.0)	4	1	0	1
Aspiration pneumonia	4 (0.7)	2	0	0	2
Respiratory compromise/ tracheal compression	2 (0.3)	1	1	0	0
Severe retrosternal pain	2 (0.3)	0	2	0	0
Bowel obstruction	2 (0.3)	0	0	0	2
Erosion4	2 (0.3)	0	14	0	1
Hemorrhage from aorta-esophageal fistula	1 (0.2)	1	0	0	0
Stricture formation	1 (0.2)	0	0	0	1
Stent-related fistula	1 (0.2)	0	1	0	0
Stent dislocation and inability to place new stent requiring rethoracotomy	1 (0.2)	0	0	1	0
Left atrial compression	1 (0.2)	0	0	0	1
Death due to esophageal necrosis at proximal stent end	1 (0.2)	1	0	0	0
Overall minor complications	333 (5.5)	15 (5.1)	10 (3.3)	0 (0)	9 (5.6)
Transient stent-related dysphagia	11 (1.8)	1	10	0	0
Stent-related ulcers	5 (0.8)	5	0	0	0
Reflux/esophagitis	3 (0.5)	0	0	0	3
Chest pain	3 (0.5)	1	0	0	2
Stent disintegration	3 (0.5)	3	0	0	0
Stent collapse/invagination	2 (0.3)	1	0	0	1
Pneumoperitoneum during endoscopy secondary to air insufflation	1 (0.2)	1	0	0	0
Atrial fibrillation related to sedation	1 (0.2)	1	0	0	0
Stent malposition	1 (0.2)	1	0	0	0
Abdominal pain	1 (0.2)	0	0	0	1
Nausea	1 (0.2)	0	0	0	1
Globus sensation	1 (0.2)	1	0	0	0
Hiccups	1 (0.2)	0	0	0	1

¹Including 30 patients in whom the number of SEPS used was not reported;

²Including 40 patients in whom the number of stents used was not reported;

³Patients can have more than one complication;

⁴Including one stent-related death. FC SEMS: Fully covered self-expandable metal stent; PC SEMS: Partially covered self-expandable metal stent; SEPS: Self-expandable plastic stent.

Table 7 Overall mortality in 643 patients treated with self-expandable stents for benign esophageal leaks, perforations and fistulae n (%)

Overall mortality	64 (10.0)
Stent-related	3 (0.5)
Sepsis-related	23 (3.6)
Multi-organ failure	5 (0.8)
Cerebral embolism/cerebrovascular accident	2 (0.3)
Heart insufficiency/cardiac disease	2 (0.3)
Pneumonia	2 (0.3)
Malignancy	2 (0.3)
Non stent-related bleeding	1 (0.2)
Respiratory insufficiency without sepsis	1 (0.2)
Pulmonary embolism	1 (0.2)
Acute respiratory distress syndrome	1 (0.2)
Pulmonary aspiration after healing of leak	1 (0.2)
Aortic dissection	1 (0.2)
Tension pneumothorax	1 (0.2)
Paraspinal abscess related to persistent fistula	1 (0.2)
Full-blown AIDS	1 (0.2)
Aspiration during contrast study	1 (0.2)
Multiple emboli caused by esophago-atrial fistula	1 (0.2)
Active euthanasia	1 (0.2)
Not specified	13 (2.0)