Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience

Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center... SUMMARY Complex benign esophageal strictures are defined by length (≥2 cm), small diameter, and stricture angulation or tortuosity. The long-term course of complex esophageal strictures based on length is currently unclear. We suspect that the esophageal stricture length might impact the effectiveness of endoscopic dilation therapy. We performed a retrospective study of all benign esophageal strictures of 2 cm or longer treated at a single center between July 1, 2010, and May 31, 2014. Primary outcomes were changed in dysphagia score at the end of follow-up compared to first dilation at our facility and the need for gastrostomy placement or esophagectomy during follow-up. Data were stratified into four subgroups according to stricture length: 20–29, 30–49, 50–99, and 100 mm or longer. Eighty-seven patients (mean age: 66 years, 54% women) were followed over a median of 40 months. Patients underwent a median of 6 dilations, averaging 0.3 dilations per month. Median dysphagia score remained unchanged at 2; 37 (43%) patients reported resolution or improved dysphagia and 50 (57%) patients reported no improvement or worsened dysphagia. Gastrostomy placement or esophagectomy was needed for 23 (26%) and 3 (3%) patients, respectively. Median degree of dysphagia at the end of follow-up did not differ between the four stricture length subgroups, yet no patient had improvement in the 100 mm or longer subgroup. More than half of patients with long benign esophageal strictures had unchanged dysphagia or developed worse dysphagia during follow-up. Long-term outcomes did not differ between different stricture lengths. INTRODUCTION Complex benign esophageal strictures, a subgroup of esophageal strictures, are defined by length (≥2 cm), small diameter preventing passage of a regular adult endoscope, and stricture characteristics, including angulation or tortuosity. These strictures are usually associated with dysphagia.1,2 Endoscopic dilation is the first-line and mainstay treatment option for these strictures, with the caveat that complex benign esophageal strictures tend to be refractory to, or recur shortly after dilation.1,2 Historically, the outcome of complex benign esophageal strictures was mainly attributed to stricture diameter and etiology, whereas the stricture length often played no role in assessment of treatment outcomes. Consequently, the few available data on long (2–5 cm) and ultralong (>5 cm) benign esophageal strictures are mostly described in very heterogeneous patient populations, that primarily included short complex esophageal strictures or even noncomplex strictures. Three small case series showed limited or no response to dilation of long strictures, including peptic, caustic, radiation, and anastomotic strictures.3–5 The effects of additional treatment modalities like electroincision, corticosteroid therapy, or stent placement are also poorly understood in this patient population.6–10 In light of these data, no dilation protocols exist for long benign esophageal strictures (LBESs); treatment decisions are mainly based on the discretion of experienced endoscopists, rather than evidence-based medicine. Our goal was to describe the outcome of LBESs (≥2 cm) in patients who underwent endoscopic dilation treatment in a tertiary endoscopy center by assessing improvement of dysphagia or need for gastrostomy or esophagectomy. PATIENTS AND METHODS Patients and procedure We performed a retrospective evaluation of all patients who underwent endoscopic evaluation or treatment at Mayo Clinic, Jacksonville, Florida, between July 1, 2010, and May 31, 2014, for LBESs. The study was approved by the Mayo Clinic Institutional Review Board. We included all upper endoscopies performed either in the advanced endoscopy hospital unit or the outpatient surgical center. Endoscopies were performed under conscious sedation administered by the gastroenterologist (T.A.W., M.R., H.C.W., and M.B.W.) using midazolam and fentanyl or under anesthesia care utilizing propofol. Upon initial endoscopy at our facility (study inclusion), all patients had dysphagia of at least grade 2.11 To assure adequate follow-up after dilation, only patients with at least 3 dilations at our facility or 1 dilation followed by a clinical follow-up of at least 30 days after dilation were included in the study. Patients with only 1 or 2 esophagogastroduodenoscopies at our facility and last clinical follow-up visit within 30 days of the procedure were excluded due to lack of follow-up information. Additionally, patients with malignant esophageal strictures and those with benign extrinsic esophageal strictures, compression, or other conditions initially coded as strictures (e.g., fistulas) were excluded. Dilations were performed according to our usual practice for any dysphagia grade of 2 or higher using Savary–Gilliard bougie dilators (Cook Medical LLC) or through-the-scope balloon dilators at the endoscopist's discretion. At the time of the study, we did not have a standardized follow-up protocol at our institution. The necessity, timing, and dilation goal for follow-up endoscopies were based on endoscopist discretion and on the impact of dysphagia on the patient's quality of life. All data were abstracted by retrospective chart review, including endoscopic procedure reports, imaging studies, and hospital or office notes. Length of esophageal stricture was measured by esophagram, when applicable, and in all patients by estimating the distal and proximal stricture dimensions during endoscopy. Etiology of esophageal stricture was defined on the basis of the patient's medical and surgical history. In each case, biopsies were obtained at study inclusion to exclude malignancy. Onset of stricture was defined as the time of the patient's first endoscopic dilation, which was either performed at our institution or at other institutions prior to presentation to our center. Patient baseline characteristics, including estimated stricture measures, were documented at the time of the first procedure at our institution. No patient had additional endoscopic procedures at other facilities while they were followed up at our facility. In addition, we recorded the number of endoscopic procedures performed prior to study inclusion. To limit recall bias, we reviewed previous medical records, which were available for most patients. Outcomes Degree of dysphagia was scored according to the Atkinson dysphagia scale: 0, able to eat normal diet or no dysphagia; 1, able to swallow some solid foods; 2, able to swallow only semi-solid foods; 3, able to swallow liquids only; and 4, unable to swallow anything or total dysphagia.11 In our experience, LBESs usually do not resolve entirely over time, but rather, improve for a certain time frame after dilation before becoming symptomatic again. Therefore, we assessed dysphagia score at study inclusion prior to dilation as all patients were symptomatic at that time point and were looking for improved quality of life. Next, we assessed dysphagia score just prior to the last recorded endoscopic dilation to have a comparable time point for dysphagia measurement. We opted not to compare immediate postdilation dysphagia grade at the different endoscopic dilation time points, primarily because we considered the postdilation interval a more important measure. The last recorded grade of dysphagia was either established at the last clinic visit in patients who had 2 or fewer endoscopic dilations at our facility and clinical follow-up of more than 30 days, or prior to the last dilation session in patients with 3 or more endoscopic dilations performed at our facility. We assumed any improvement of dysphagia over time would indicate a successful outcome, even if residual dysphagia was still present, as we did not define an end point of resolved dysphagia to be realistic in such complex LBESs. We also counted the total number of dilations performed, from first dilation at our institution or prior to presentation to our institution to the last dilation or follow-up endoscopy, and reported the ratio of dilations per months of follow-up. Other recorded outcomes included lack of improvement or worsening of dysphagia and need for gastrostomy or esophagectomy. We stratified the data into four subgroups according to stricture length: 20 to 29 mm, 30 to 49 mm, 50 to 99 mm, and 100 mm or longer, to achieve a representative number of patients in each subgroup. Statistical analysis Continuous variables are presented as mean (SD) if normally distributed or as median (interquartile range [IQR]) if not normally distributed. Results were rounded to the nearest percentage point to facilitate text presentation. Baseline criteria of included patients and patients excluded due to missing follow-up were compared using t test. These excluded 22 patients without follow-up (only 1 EGD at our facility and last follow-up visit ≤30 days after dilation). RESULTS A total of 138 patients were diagnosed with esophageal stricture of 20 mm or longer based on the endoscopy report. Patients with malignant esophageal strictures (n = 15) were excluded, as were patients with benign extrinsic esophageal strictures, compression, nonsymptomatic strictures, and other conditions initially coded as stricture (n = 14). Patients with inadequate follow-up were also excluded (n = 22; Fig 1). Fig. 1 View largeDownload slide Selection of study population. EGD indicates esphagogastroduodenoscopy. Fig. 1 View largeDownload slide Selection of study population. EGD indicates esphagogastroduodenoscopy. A total of 87 patients (mean [SD] age 66 [16] years; 47 [54%] women) were included in the final evaluation, with an available median follow-up of 40 (23–485) months. Patients had a median dysphagia score of 2 (2–4) upon study inclusion. The most common stricture etiologies were peptic (22 [25.3%]), radiation (21 [24.1%]), anastomotic (7 [8.0%]), ablation (9 [10.3%]), and endoscopic mucosal resection (8 [9.2%]); strictures were evenly distributed in the esophagus: 29 (33.3%) upper, 24 (27.6%) middle, and 34 (39.1%) lower esophagus (Table 1). Mean stricture length and diameter at study inclusion were 43 (41) mm and 8.4 (3.5) mm, respectively. Patients underwent a median of 6 (4–63) dilations, averaging 0.3 (0.2) dilations per month (Table 2). A minority of patients underwent argon plasma tissue vaporization, stent placement, corticosteroid, and mitomycin C application in addition to dilation (data not shown). Table 1 Patient baseline demographics and clinical characteristics Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia; ‡All performed for esophageal nodular lesions include adenocarcinoma (1), squamous cell carcinoma (2), Barrett's esophagus with dysplasia (3) and without dysplasia (2); §Remnant cartilage, dyskeratosis congenital; ¶Lichen planus (7), pityriasis lichenoides et varioliformis acuta (1), Crohn disease (1). GERD, gastroesophageal reflux disease; IQR, interquartile range; PDT, photodynamic therapy; PPI, proton pump inhibitor; RFA, radiofrequency ablation. View Large Table 1 Patient baseline demographics and clinical characteristics Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia; ‡All performed for esophageal nodular lesions include adenocarcinoma (1), squamous cell carcinoma (2), Barrett's esophagus with dysplasia (3) and without dysplasia (2); §Remnant cartilage, dyskeratosis congenital; ¶Lichen planus (7), pityriasis lichenoides et varioliformis acuta (1), Crohn disease (1). GERD, gastroesophageal reflux disease; IQR, interquartile range; PDT, photodynamic therapy; PPI, proton pump inhibitor; RFA, radiofrequency ablation. View Large Table 2 Overall outcomes of stricture dilation Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  †16 of 87 patients had only 1 EGD at our facility; ‡Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. EGD, esophagogastroduodenoscopy; IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large Table 2 Overall outcomes of stricture dilation Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  †16 of 87 patients had only 1 EGD at our facility; ‡Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. EGD, esophagogastroduodenoscopy; IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large During follow-up, 37 (42.5%) patients had resolution or improvement of dysphagia and 50 (57.5%) reported no improvement or worsened dysphagia, for which 23 (26.4%) patients became gastrostomy-dependent and 3 (3.4%) required esophagectomy. These proportions were similar when patients (69 [79.3%]) who had more than 3 dilations at our facility were compared with those (14 [16.1%]) who had only 1 or 2 dilations with adequate follow-up at our facility. Stricture diameter improved slightly during follow-up from 8.4 (3.5) mm to 9.5 (4.3) mm, and stricture length remained unchanged (Table 2). Results stratified by stricture length Stricture diameter, number of dilations, follow-up, and median degree of dysphagia at the end of follow-up did not differ notably when patients were divided into the 4 stricture length subgroups: 20 to 29 mm, 30 to 49 mm, 50 to 99 mm, and 100 mm or longer (Table 3). Approximately half of the patients in the 20 to 29 mm, 30 to 49 mm, and 50 to 99 mm subgroups responded to dilation with improvement or resolution of dysphagia; however, this did not occur in the 8 patients with strictures of 100 mm or longer (P = 0.06), and they did required more frequent dilations 0.5/months (P = 0.03). The proportion of patients who became gastrostomy-dependent was comparable throughout the subgroups. Table 3 Outcomes stratified by stricture length Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. If median and IQR are displayed a P-value is calculated based on the Kruskal-Wallis test. If mean and SD are displayed the P-value is based on the one-way ANOVA. IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large Table 3 Outcomes stratified by stricture length Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. If median and IQR are displayed a P-value is calculated based on the Kruskal-Wallis test. If mean and SD are displayed the P-value is based on the one-way ANOVA. IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large DISCUSSION Treatment algorithms for LBESs are often extrapolated from noncomplex strictures or limited to certain stricture etiologies. In general, the natural history of LBES is poorly understood, further limiting formulation of treatment algorithms for such strictures. This study focused on treatment outcomes of LBES, which we further stratified by stricture length. It is intuitive to suspect longer benign strictures have worse outcomes than shorter strictures. We found more than half of our patients with LBES ranging from 20 to 200 mm experienced no improvement or worsened dysphagia, and approximately one-quarter were gastrostomy-dependent. Stratifying the stricture length range of 20 to 200 mm into subgroups did not result in notable stricture length-dependent outcomes. In particular, we found no obvious differences in dysphagia scores at the end of follow-up, proportion of patients with unchanged or worse dysphagia, and proportion of patients requiring gastrostomy placement between the stricture-length subgroups. Only patients with strictures of 100 mm or longer showed no improvement following stricture dilation. Importantly, we found patients with LBESs of 20 to 29 mm had substantially worse outcomes compared to previously published data on complex benign esophageal strictures shorter than 20 mm.2,12 Comparable data were reported in only 3 studies, which included subgroups of LBES.3–5 Ikeya and colleagues3 showed anastomotic strictures (mean 30.8 mm) in 6 patients failed to improve following dilation therapy over a mean follow-up of 51 months. Chiu et al.4 reported on 25 patients with mainly corrosive, anastomotic, and radiation strictures ranging from 10 to 150 mm. All 21 patients with strictures shorter than 80 mm had resolution of dysphagia after dilation for 12 months, whereas 3 of 4 patients with strictures 80 mm or longer (75%) developed dysphagia within 12 months after dilation, which is partly consistent with our findings.4 Only Qureshi et al.5 showed improvement of dysphagia in caustic and peptic strictures longer than 60 mm following dilation, although these patients required more treatment sessions than patients with strictures shorter than 60 mm to achieve improvement of dysphagia over a maximum follow-up of 20 months (3 dilations vs. 7 dilations, total of 26 patients).5 The goal of dilation is to improve the quality of life of patients by decreasing the grade of dysphagia. At the same time, risks and benefits of dilation need to be addressed for each LBES. Unrealistic goals and the need for gastrostomy placement if the oral calorie intake is inadequate should be addressed. Currently, there are no data on which treatment physicians can rely on when discussing the goals of dilation care with patients with LBESs. Patients with such strictures are frequently malnourished, reflected by sarcopenia; therefore, it is important to discuss methods of alternative caloric intake early in the treatment. In this study, only about half of patients showed improvement in caloric intake. Based on our limited data, we cannot state which exact stricture failed to improve after dilation; however, our data indicates early discussion of alternative nutrition routes may be important. It remains unclear if more aggressive or more frequent dilation or the addition of adjuvant treatment like incisional therapy, corticosteroid injection, or use of mitomycin C would be beneficial for treatment of LBES.7,13–17 A recent study by Grooteman and colleagues18 suggested that more aggressive dilation of up to 6 mm increments from the point of initial resistance is safe. However, these data, and the data of most previous publications13-17 cannot be extrapolated to LBES. This limitation is particularly important when addressing long-term outcome goals, which are improvement of dysphagia and avoidance of further complications.18,19 The fact that most patients in this study were dilated over months to years and showed no different outcome when compared with patients with shorter follow-up data indicates the chronicity of such strictures. This study is mainly limited by its retrospective nature. Including stricture dilations predating the time of our study inclusion, which we chose as the first dilations at our institution, raises risk of recall bias. Consequently, we did not have all available time points of dilations for most patients, but rather the summary of previous dilation sessions, which further limits the interpretation of our data. Therefore, survival analyses or incidence rate estimations for failure or success of dilation could not be performed. Additionally, none of the patients underwent a formal dilation algorithm. All dilations were based on improvement of the patient's quality of life, a subjective measure, and the endoscopist's discretion, which further limits the interpretation and generalizability of our data. However, such an approach is common practice in most tertiary endoscopy centers, with a treatment algorithm by Siersema et al.20 We also did not use a standardized questionnaire for dysphagia at that time; however, the dysphagia score, which is eventually the most important measure of quality of life, is recorded prior to dilation sessions or during a clinic visit in our practice. Therefore, we interpreted the dysphagia score as the only valid and adequate outcome measure in this study. One can also argue dilating at a mean of 0.3 dilations per month is not adequate to achieve treatment success, particularly as weekly or biweekly dilation sessions have been suggested in treatment protocols in centers with high expertise.20 However, such stringent dilation protocols have not been shown to be more successful. Our patient cohort has a high proportion of refractory and recurrent esophageal strictures, with 69 (79.3%) patients requiring 3 or more dilations, which raises the concern for selection bias. However, we included consecutive patients with long benign esophageal strictures. Eligible patients were only excluded due to inadequate follow-up (22 of 138). One can argue patients who were lost to follow-up may have had a better response to dilation, and subsequently our patient cohort is skewed and over represents recurrent and refractory strictures. If such a selection bias has occurred, we doubt the results of this study would have been substantially impacted for 2 reasons. First, patients who were lost due to missing follow-up were missing completely at random when assessed for baseline characteristics. Second, of all included patients, 14 (16.1%) had only 1 or 2 dilations. And there was no difference in outcome between these 14 patients and those with more than 3 dilations. We suspect a higher proportion of patients with LBESs have recurrent and refractory strictures. To our knowledge, this is the first study addressing the importance of stricture length in LBESs. Strictures of 20 mm or longer had substantially worse outcomes compared to those reported in the literature for shorter complex benign strictures. For most patients with LBES, dysphagia did not improve or even worsened during follow-up, and a substantial proportion required gastrostomy. Long-term outcomes did not appear to differ between different stricture lengths; a prospective study to define the natural history of LBES would aid future shared decision-making, weighing individual benefits against risks of treatment regimens for these patients. Notes Presented at Digestive Diseases Week 2016, May 21–24, 2016, San Diego, California; American College of Gastroenterology 2016 Annual Scientific Meeting, October 14–19, 2016, Las Vegas, Nevada; and the 24th United European Gastroenterology Week October 15–19, 2016, Vienna, Austria. Portions of this manuscript have been published in abstract form: Simons-Linares R, Bartel M J, Patel K, Brahmbhatt B, Bhurwal A, Woodward T A. Tu1231: The long-term outcome of long complex benign esophageal strictures. Gastrointest Endosc 2016; 83: AB1–AB694. Conflict of interest: Dr Wallace reports consulting income from Olympus and grant support from Boston Scientific, Olympus, Medtronic, and Cosmo pharmaceuticals. None of the other authors have conflicts of interest to disclose. Source and role of funding: None. References 1 Kochman M L, McClave S A, Boyce H W. The refractory and the recurrent esophageal stricture: a definition. Gastrointest Endosc  2005; 62: 474– 5. Google Scholar CrossRef Search ADS PubMed  2 Lew R J, Kochman M L. A review of endoscopic methods of esophageal dilation. J Clin Gastroenterol  2002; 35: 117– 26. Google Scholar CrossRef Search ADS PubMed  3 Ikeya T, Ohwada S, Ogawa T et al.   Endoscopic balloon dilation for benign esophageal anastomotic stricture: factors influencing its effectiveness. Hepatogastroenterology  1999; 46: 959– 66. Google Scholar PubMed  4 Chiu Y C, Hsu C C, Chiu KW et al.   Factors influencing clinical applications of endoscopic balloon dilation for benign esophageal strictures. Endoscopy  2004; 36: 595– 600. Google Scholar CrossRef Search ADS PubMed  5 Qureshi S, Ghazanfar S, Leghari A, Tariq F, Niaz S K, Quraishy M S. Benign esophageal strictures: behaviour, pattern and response to dilatation. J Pak Med Assoc  2010; 60: 656– 60. Google Scholar PubMed  6 Hordijk M L, Siersema P D, Tilanus H W, Kuipers E J. Electrocautery therapy for refractory anastomotic strictures of the esophagus. Gastrointest Endosc  2006; 63: 157– 63. Google Scholar CrossRef Search ADS PubMed  7 Kochhar R, Ray J D, Sriram P V, Kumar S, Singh K. Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures. Gastrointest Endosc  1999; 49: 509– 13. Google Scholar CrossRef Search ADS PubMed  8 Kochhar R, Makharia GK. Usefulness of intralesional triamcinolone in treatment of benign esophageal strictures. Gastrointest Endosc  2002; 56: 829– 34. Google Scholar CrossRef Search ADS PubMed  9 Kim J H, Song H Y, Choi E K, Kim K R, Shin J H, Lim J O. Temporary metallic stent placement in the treatment of refractory benign esophageal strictures: results and factors associated with outcome in 55 patients. Eur Radiol  2009; 19: 384– 90. Google Scholar CrossRef Search ADS PubMed  10 Repici A, Hassan C, Sharma P, Conio M, Siersema P. Systematic review: the role of Self-Expanding plastic stents for benign oesophageal strictures. Aliment Pharmacol Ther  2010; 31: 1268– 75. Google Scholar CrossRef Search ADS PubMed  11 Atkinson M. Diseases of the alimentary system. Dysphagia Br Med J  1977; 1: 91– 3. Google Scholar PubMed  12 de Wijkerslooth L R, Vleggaar F P, Siersema P D. Endoscopic management of difficult or recurrent esophageal strictures. Am J Gastroenterol  2011; 106: 2080– 91. Google Scholar CrossRef Search ADS PubMed  13 Bartel M J, Seeger K, Jeffers K et al.   Topical Mitomycin C application in the treatment of refractory benign esophageal strictures in adults and comprehensive literature review. Dig Liver Dis  2016; 48: 1058– 65. Google Scholar CrossRef Search ADS PubMed  14 Hirdes M M, van Hooft J E, Koornstra J J et al.   Endoscopic corticosteroid injections do not reduce dysphagia after endoscopic dilation therapy in patients with benign esophagogastric anastomotic strictures. Clin Gastroenterol Hepatol  2013; 11: 795– 801.e1. Google Scholar CrossRef Search ADS PubMed  15 Ramage J I Jr., Rumalla A, Baron T H et al.   A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures. Am J Gastroenterol  2005; 100: 2419– 25. Google Scholar CrossRef Search ADS PubMed  16 Hordijk M L, van Hooft J E, Hansen B E, Fockens P, Kuipers E J. A randomized comparison of electrocautery incision with Savary bougienage for relief of anastomotic gastroesophageal strictures. Gastrointest Endosc  2009; 70: 849– 55. Google Scholar CrossRef Search ADS PubMed  17 Simmons D T, Baron T H. Electroincision of refractory esophagogastric anastomotic strictures. Dis Esophagus  2006; 19: 410– 4. Google Scholar CrossRef Search ADS PubMed  18 Grooteman K V, Wong Kee Song L M, Vleggaar F P, Siersema P D, Baron T H. Non-adherence to the rule of 3 does not increase the risk of adverse events in esophageal dilation. Gastrointest Endosc  2017; 85: 332– 337.e1. Google Scholar CrossRef Search ADS PubMed  19 Richter J E. Rule of three for esophageal dilation: like the tortoise versus the rabbit, low and slow is our friend and our patients' win. Gastrointest Endosc  2017; 85: 338– 9. Google Scholar CrossRef Search ADS PubMed  20 Siersema P D, de Wijkerslooth L R. Dilation of refractory benign esophageal strictures. Gastrointest Endosc  2009; 70: 1000– 12. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diseases of the Esophagus Oxford University Press

Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience

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The International Society for Diseases of the Esophagus
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© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.
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1120-8694
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1442-2050
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10.1093/dote/doy040
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Abstract

SUMMARY Complex benign esophageal strictures are defined by length (≥2 cm), small diameter, and stricture angulation or tortuosity. The long-term course of complex esophageal strictures based on length is currently unclear. We suspect that the esophageal stricture length might impact the effectiveness of endoscopic dilation therapy. We performed a retrospective study of all benign esophageal strictures of 2 cm or longer treated at a single center between July 1, 2010, and May 31, 2014. Primary outcomes were changed in dysphagia score at the end of follow-up compared to first dilation at our facility and the need for gastrostomy placement or esophagectomy during follow-up. Data were stratified into four subgroups according to stricture length: 20–29, 30–49, 50–99, and 100 mm or longer. Eighty-seven patients (mean age: 66 years, 54% women) were followed over a median of 40 months. Patients underwent a median of 6 dilations, averaging 0.3 dilations per month. Median dysphagia score remained unchanged at 2; 37 (43%) patients reported resolution or improved dysphagia and 50 (57%) patients reported no improvement or worsened dysphagia. Gastrostomy placement or esophagectomy was needed for 23 (26%) and 3 (3%) patients, respectively. Median degree of dysphagia at the end of follow-up did not differ between the four stricture length subgroups, yet no patient had improvement in the 100 mm or longer subgroup. More than half of patients with long benign esophageal strictures had unchanged dysphagia or developed worse dysphagia during follow-up. Long-term outcomes did not differ between different stricture lengths. INTRODUCTION Complex benign esophageal strictures, a subgroup of esophageal strictures, are defined by length (≥2 cm), small diameter preventing passage of a regular adult endoscope, and stricture characteristics, including angulation or tortuosity. These strictures are usually associated with dysphagia.1,2 Endoscopic dilation is the first-line and mainstay treatment option for these strictures, with the caveat that complex benign esophageal strictures tend to be refractory to, or recur shortly after dilation.1,2 Historically, the outcome of complex benign esophageal strictures was mainly attributed to stricture diameter and etiology, whereas the stricture length often played no role in assessment of treatment outcomes. Consequently, the few available data on long (2–5 cm) and ultralong (>5 cm) benign esophageal strictures are mostly described in very heterogeneous patient populations, that primarily included short complex esophageal strictures or even noncomplex strictures. Three small case series showed limited or no response to dilation of long strictures, including peptic, caustic, radiation, and anastomotic strictures.3–5 The effects of additional treatment modalities like electroincision, corticosteroid therapy, or stent placement are also poorly understood in this patient population.6–10 In light of these data, no dilation protocols exist for long benign esophageal strictures (LBESs); treatment decisions are mainly based on the discretion of experienced endoscopists, rather than evidence-based medicine. Our goal was to describe the outcome of LBESs (≥2 cm) in patients who underwent endoscopic dilation treatment in a tertiary endoscopy center by assessing improvement of dysphagia or need for gastrostomy or esophagectomy. PATIENTS AND METHODS Patients and procedure We performed a retrospective evaluation of all patients who underwent endoscopic evaluation or treatment at Mayo Clinic, Jacksonville, Florida, between July 1, 2010, and May 31, 2014, for LBESs. The study was approved by the Mayo Clinic Institutional Review Board. We included all upper endoscopies performed either in the advanced endoscopy hospital unit or the outpatient surgical center. Endoscopies were performed under conscious sedation administered by the gastroenterologist (T.A.W., M.R., H.C.W., and M.B.W.) using midazolam and fentanyl or under anesthesia care utilizing propofol. Upon initial endoscopy at our facility (study inclusion), all patients had dysphagia of at least grade 2.11 To assure adequate follow-up after dilation, only patients with at least 3 dilations at our facility or 1 dilation followed by a clinical follow-up of at least 30 days after dilation were included in the study. Patients with only 1 or 2 esophagogastroduodenoscopies at our facility and last clinical follow-up visit within 30 days of the procedure were excluded due to lack of follow-up information. Additionally, patients with malignant esophageal strictures and those with benign extrinsic esophageal strictures, compression, or other conditions initially coded as strictures (e.g., fistulas) were excluded. Dilations were performed according to our usual practice for any dysphagia grade of 2 or higher using Savary–Gilliard bougie dilators (Cook Medical LLC) or through-the-scope balloon dilators at the endoscopist's discretion. At the time of the study, we did not have a standardized follow-up protocol at our institution. The necessity, timing, and dilation goal for follow-up endoscopies were based on endoscopist discretion and on the impact of dysphagia on the patient's quality of life. All data were abstracted by retrospective chart review, including endoscopic procedure reports, imaging studies, and hospital or office notes. Length of esophageal stricture was measured by esophagram, when applicable, and in all patients by estimating the distal and proximal stricture dimensions during endoscopy. Etiology of esophageal stricture was defined on the basis of the patient's medical and surgical history. In each case, biopsies were obtained at study inclusion to exclude malignancy. Onset of stricture was defined as the time of the patient's first endoscopic dilation, which was either performed at our institution or at other institutions prior to presentation to our center. Patient baseline characteristics, including estimated stricture measures, were documented at the time of the first procedure at our institution. No patient had additional endoscopic procedures at other facilities while they were followed up at our facility. In addition, we recorded the number of endoscopic procedures performed prior to study inclusion. To limit recall bias, we reviewed previous medical records, which were available for most patients. Outcomes Degree of dysphagia was scored according to the Atkinson dysphagia scale: 0, able to eat normal diet or no dysphagia; 1, able to swallow some solid foods; 2, able to swallow only semi-solid foods; 3, able to swallow liquids only; and 4, unable to swallow anything or total dysphagia.11 In our experience, LBESs usually do not resolve entirely over time, but rather, improve for a certain time frame after dilation before becoming symptomatic again. Therefore, we assessed dysphagia score at study inclusion prior to dilation as all patients were symptomatic at that time point and were looking for improved quality of life. Next, we assessed dysphagia score just prior to the last recorded endoscopic dilation to have a comparable time point for dysphagia measurement. We opted not to compare immediate postdilation dysphagia grade at the different endoscopic dilation time points, primarily because we considered the postdilation interval a more important measure. The last recorded grade of dysphagia was either established at the last clinic visit in patients who had 2 or fewer endoscopic dilations at our facility and clinical follow-up of more than 30 days, or prior to the last dilation session in patients with 3 or more endoscopic dilations performed at our facility. We assumed any improvement of dysphagia over time would indicate a successful outcome, even if residual dysphagia was still present, as we did not define an end point of resolved dysphagia to be realistic in such complex LBESs. We also counted the total number of dilations performed, from first dilation at our institution or prior to presentation to our institution to the last dilation or follow-up endoscopy, and reported the ratio of dilations per months of follow-up. Other recorded outcomes included lack of improvement or worsening of dysphagia and need for gastrostomy or esophagectomy. We stratified the data into four subgroups according to stricture length: 20 to 29 mm, 30 to 49 mm, 50 to 99 mm, and 100 mm or longer, to achieve a representative number of patients in each subgroup. Statistical analysis Continuous variables are presented as mean (SD) if normally distributed or as median (interquartile range [IQR]) if not normally distributed. Results were rounded to the nearest percentage point to facilitate text presentation. Baseline criteria of included patients and patients excluded due to missing follow-up were compared using t test. These excluded 22 patients without follow-up (only 1 EGD at our facility and last follow-up visit ≤30 days after dilation). RESULTS A total of 138 patients were diagnosed with esophageal stricture of 20 mm or longer based on the endoscopy report. Patients with malignant esophageal strictures (n = 15) were excluded, as were patients with benign extrinsic esophageal strictures, compression, nonsymptomatic strictures, and other conditions initially coded as stricture (n = 14). Patients with inadequate follow-up were also excluded (n = 22; Fig 1). Fig. 1 View largeDownload slide Selection of study population. EGD indicates esphagogastroduodenoscopy. Fig. 1 View largeDownload slide Selection of study population. EGD indicates esphagogastroduodenoscopy. A total of 87 patients (mean [SD] age 66 [16] years; 47 [54%] women) were included in the final evaluation, with an available median follow-up of 40 (23–485) months. Patients had a median dysphagia score of 2 (2–4) upon study inclusion. The most common stricture etiologies were peptic (22 [25.3%]), radiation (21 [24.1%]), anastomotic (7 [8.0%]), ablation (9 [10.3%]), and endoscopic mucosal resection (8 [9.2%]); strictures were evenly distributed in the esophagus: 29 (33.3%) upper, 24 (27.6%) middle, and 34 (39.1%) lower esophagus (Table 1). Mean stricture length and diameter at study inclusion were 43 (41) mm and 8.4 (3.5) mm, respectively. Patients underwent a median of 6 (4–63) dilations, averaging 0.3 (0.2) dilations per month (Table 2). A minority of patients underwent argon plasma tissue vaporization, stent placement, corticosteroid, and mitomycin C application in addition to dilation (data not shown). Table 1 Patient baseline demographics and clinical characteristics Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia; ‡All performed for esophageal nodular lesions include adenocarcinoma (1), squamous cell carcinoma (2), Barrett's esophagus with dysplasia (3) and without dysplasia (2); §Remnant cartilage, dyskeratosis congenital; ¶Lichen planus (7), pityriasis lichenoides et varioliformis acuta (1), Crohn disease (1). GERD, gastroesophageal reflux disease; IQR, interquartile range; PDT, photodynamic therapy; PPI, proton pump inhibitor; RFA, radiofrequency ablation. View Large Table 1 Patient baseline demographics and clinical characteristics Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  Demographics and clinical characteristics  N = 87  Age, mean (SD)  66 (16)  Women, no. (%)  47 (54.0)  GERD, no. (%)  61 (70.1)  PPI use, no. (%)  69 (79.3)  Dysphagia present at study inclusion, no. (%)  87 (100.0)  Dysphagia score at study inclusion, median (IQR)†  2 (2–4)  Duration between first dilation and last dilation/follow-up, median (IQR), month  40 (23–485)  Duration between first dilation at our facility to the last dilation/follow-up, median (IQR), month  16 (5–47)  Patients with only 1 or 2 dilations, no. (%)  14 (16.1)  Patients with >2 dilation, no. (%)  69 (79.3)  Stricture etiology, no. (%)  Peptic  22 (25.3)  Radiation  21 (24.1)  Anastomotic  7 (8.0)  Radiation and anastomotic  2 (2.3)  Ablation (RFA, PDT, cryotherapy)  9 (10.3)  Endoscopic mucosal resection‡  8 (9.2)  Eosinophilic esophagitis  6 (6.9)  Acute esophageal necrosis  1 (1.1)  Congenital§  2 (2.3)  Dermatologic/systemic conditions¶  9 (10.3)  Location of most proximal part of the stricture measured from the incisors, no. (%)  Upper 18–23 cm  29 (33.3)  Middle 24–31 cm  24 (27.6)  Lower 32–40 cm  34 (39.1)  †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia; ‡All performed for esophageal nodular lesions include adenocarcinoma (1), squamous cell carcinoma (2), Barrett's esophagus with dysplasia (3) and without dysplasia (2); §Remnant cartilage, dyskeratosis congenital; ¶Lichen planus (7), pityriasis lichenoides et varioliformis acuta (1), Crohn disease (1). GERD, gastroesophageal reflux disease; IQR, interquartile range; PDT, photodynamic therapy; PPI, proton pump inhibitor; RFA, radiofrequency ablation. View Large Table 2 Overall outcomes of stricture dilation Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  †16 of 87 patients had only 1 EGD at our facility; ‡Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. EGD, esophagogastroduodenoscopy; IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large Table 2 Overall outcomes of stricture dilation Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  Outcomes  N = 87  Dilations, median (IQR)  6 (4–63)  Dilations per month, mean (SD)  0.3 (0.2)  Stricture dimensions, mm, mean (SD)  Stricture diameter at study inclusion  8.4 (3.5)  Stricture diameter at last EGD  9.5 (4.3)  Stricture length at study inclusion  43 (41)†  Stricture length at last EGD  42.5 (47)†  Esophagectomy, no. (%)  3 (3.4)  PEG-dependent, no. (%)  23 (26.4)  Dysphagia score at end of follow-up, median (IQR)‡  2 (1–4)  No or improved dysphagia at end of follow-up, no. (%)  37 (42.5)  No dysphagia at end of follow-up  18 (20.7)  Unchanged or worse dysphagia at end of follow-up, no. (%)  50 (57.5)  Unchanged dysphagia score  38 (43.7)  PEG-dependent  14 (16.1)  Needed an esophagectomy  2 (2.3)  Worse dysphagia score  12 (13.8)  PEG-dependent  9 (10.3)  Needed an esophagectomy  1 (1.1)  Dysphagia score at end of follow-up, median (IQR)  2 (1–4)  †16 of 87 patients had only 1 EGD at our facility; ‡Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. EGD, esophagogastroduodenoscopy; IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large During follow-up, 37 (42.5%) patients had resolution or improvement of dysphagia and 50 (57.5%) reported no improvement or worsened dysphagia, for which 23 (26.4%) patients became gastrostomy-dependent and 3 (3.4%) required esophagectomy. These proportions were similar when patients (69 [79.3%]) who had more than 3 dilations at our facility were compared with those (14 [16.1%]) who had only 1 or 2 dilations with adequate follow-up at our facility. Stricture diameter improved slightly during follow-up from 8.4 (3.5) mm to 9.5 (4.3) mm, and stricture length remained unchanged (Table 2). Results stratified by stricture length Stricture diameter, number of dilations, follow-up, and median degree of dysphagia at the end of follow-up did not differ notably when patients were divided into the 4 stricture length subgroups: 20 to 29 mm, 30 to 49 mm, 50 to 99 mm, and 100 mm or longer (Table 3). Approximately half of the patients in the 20 to 29 mm, 30 to 49 mm, and 50 to 99 mm subgroups responded to dilation with improvement or resolution of dysphagia; however, this did not occur in the 8 patients with strictures of 100 mm or longer (P = 0.06), and they did required more frequent dilations 0.5/months (P = 0.03). The proportion of patients who became gastrostomy-dependent was comparable throughout the subgroups. Table 3 Outcomes stratified by stricture length Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. If median and IQR are displayed a P-value is calculated based on the Kruskal-Wallis test. If mean and SD are displayed the P-value is based on the one-way ANOVA. IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large Table 3 Outcomes stratified by stricture length Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    Stricture length at study inclusion  20–29 mm (n = 41)  30–49 mm (n = 21)  50–99 mm (n = 17)  ≥100 mm (n = 8)  P-value  Stricture diameter, mm, mean (SD)  8.9 (3.8)  8.6 (3.6)  7.3 (2.9)  7.8 (3.0)  0.42  No. of dilations, median (IQR)  6 (4–11)  6 (3–14)  9 (6–16)  12 (5–21)  0.22  Total follow-up time, median (IQR), month  40 (23–62)  43 (25–70)  35 (14–80)  41 (18–63)  0.86  No. of dilations/months follow-up, mean (SD)  0.3 (0.2)  0.2 (0.2)  0.3 (0.2)  0.5 (0.6)  0.03  Dysphagia score at study inclusion, median (IQR)†  2 (2–3)  2 (2–3)  2 (2–2.5)  2.5 (2–3)  0.51  Dysphagia score at end of follow-up, median (IQR)†  2 (1–3)  2 (0–3)  2 (1.5–2)  2 (2–3)  0.49  No or improved dysphagia at end of follow-up, no. (%)  17 (41.5)  11 (52.4)  9 (52.9)  0 (0.0)  0.057     No dysphagia at end of follow-up  8 (19.5)  8 (38.1)  2 (11.8)  0 (0.0)    Unchanged or worse dysphagia at end of follow-up, no. (%)  24 (58.5)  10 (47.6)  8 (47.1)  8 (100.0)  0.057  Unchanged dysphagia score  18 (43.9)  6 (28.6)  7 (41.2)  7 (87.5)       PEG-dependent  7 (17.1)  4 (19.0)  2 (11.8)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  1 (12.5)    Worse dysphagia score  6 (14.6)  4 (19.0)  1 (5.9)  1 (12.5)       PEG-dependent  4 (9.8)  3 (14.3)  1 (5.9)  1 (12.5)       Needed an esophagectomy  1 (2.4)  0 (0.0)  0 (0.0)  0 (0.0)    Need for PEG, no. (%)  11 (26.8)  7 (33.3)  3 (17.6)  2 (25.0)  0.753  Need for esophagectomy, no. (%)  2 (4.9)  0 (0.0)  0 (0.0)  1 (12.5)    †Dysphagia score ranges from 0 to 4, with higher scores indicating worse dysphagia. If median and IQR are displayed a P-value is calculated based on the Kruskal-Wallis test. If mean and SD are displayed the P-value is based on the one-way ANOVA. IQR, interquartile range; PEG, percutaneous endoscopic gastrostomy. View Large DISCUSSION Treatment algorithms for LBESs are often extrapolated from noncomplex strictures or limited to certain stricture etiologies. In general, the natural history of LBES is poorly understood, further limiting formulation of treatment algorithms for such strictures. This study focused on treatment outcomes of LBES, which we further stratified by stricture length. It is intuitive to suspect longer benign strictures have worse outcomes than shorter strictures. We found more than half of our patients with LBES ranging from 20 to 200 mm experienced no improvement or worsened dysphagia, and approximately one-quarter were gastrostomy-dependent. Stratifying the stricture length range of 20 to 200 mm into subgroups did not result in notable stricture length-dependent outcomes. In particular, we found no obvious differences in dysphagia scores at the end of follow-up, proportion of patients with unchanged or worse dysphagia, and proportion of patients requiring gastrostomy placement between the stricture-length subgroups. Only patients with strictures of 100 mm or longer showed no improvement following stricture dilation. Importantly, we found patients with LBESs of 20 to 29 mm had substantially worse outcomes compared to previously published data on complex benign esophageal strictures shorter than 20 mm.2,12 Comparable data were reported in only 3 studies, which included subgroups of LBES.3–5 Ikeya and colleagues3 showed anastomotic strictures (mean 30.8 mm) in 6 patients failed to improve following dilation therapy over a mean follow-up of 51 months. Chiu et al.4 reported on 25 patients with mainly corrosive, anastomotic, and radiation strictures ranging from 10 to 150 mm. All 21 patients with strictures shorter than 80 mm had resolution of dysphagia after dilation for 12 months, whereas 3 of 4 patients with strictures 80 mm or longer (75%) developed dysphagia within 12 months after dilation, which is partly consistent with our findings.4 Only Qureshi et al.5 showed improvement of dysphagia in caustic and peptic strictures longer than 60 mm following dilation, although these patients required more treatment sessions than patients with strictures shorter than 60 mm to achieve improvement of dysphagia over a maximum follow-up of 20 months (3 dilations vs. 7 dilations, total of 26 patients).5 The goal of dilation is to improve the quality of life of patients by decreasing the grade of dysphagia. At the same time, risks and benefits of dilation need to be addressed for each LBES. Unrealistic goals and the need for gastrostomy placement if the oral calorie intake is inadequate should be addressed. Currently, there are no data on which treatment physicians can rely on when discussing the goals of dilation care with patients with LBESs. Patients with such strictures are frequently malnourished, reflected by sarcopenia; therefore, it is important to discuss methods of alternative caloric intake early in the treatment. In this study, only about half of patients showed improvement in caloric intake. Based on our limited data, we cannot state which exact stricture failed to improve after dilation; however, our data indicates early discussion of alternative nutrition routes may be important. It remains unclear if more aggressive or more frequent dilation or the addition of adjuvant treatment like incisional therapy, corticosteroid injection, or use of mitomycin C would be beneficial for treatment of LBES.7,13–17 A recent study by Grooteman and colleagues18 suggested that more aggressive dilation of up to 6 mm increments from the point of initial resistance is safe. However, these data, and the data of most previous publications13-17 cannot be extrapolated to LBES. This limitation is particularly important when addressing long-term outcome goals, which are improvement of dysphagia and avoidance of further complications.18,19 The fact that most patients in this study were dilated over months to years and showed no different outcome when compared with patients with shorter follow-up data indicates the chronicity of such strictures. This study is mainly limited by its retrospective nature. Including stricture dilations predating the time of our study inclusion, which we chose as the first dilations at our institution, raises risk of recall bias. Consequently, we did not have all available time points of dilations for most patients, but rather the summary of previous dilation sessions, which further limits the interpretation of our data. Therefore, survival analyses or incidence rate estimations for failure or success of dilation could not be performed. Additionally, none of the patients underwent a formal dilation algorithm. All dilations were based on improvement of the patient's quality of life, a subjective measure, and the endoscopist's discretion, which further limits the interpretation and generalizability of our data. However, such an approach is common practice in most tertiary endoscopy centers, with a treatment algorithm by Siersema et al.20 We also did not use a standardized questionnaire for dysphagia at that time; however, the dysphagia score, which is eventually the most important measure of quality of life, is recorded prior to dilation sessions or during a clinic visit in our practice. Therefore, we interpreted the dysphagia score as the only valid and adequate outcome measure in this study. One can also argue dilating at a mean of 0.3 dilations per month is not adequate to achieve treatment success, particularly as weekly or biweekly dilation sessions have been suggested in treatment protocols in centers with high expertise.20 However, such stringent dilation protocols have not been shown to be more successful. Our patient cohort has a high proportion of refractory and recurrent esophageal strictures, with 69 (79.3%) patients requiring 3 or more dilations, which raises the concern for selection bias. However, we included consecutive patients with long benign esophageal strictures. Eligible patients were only excluded due to inadequate follow-up (22 of 138). One can argue patients who were lost to follow-up may have had a better response to dilation, and subsequently our patient cohort is skewed and over represents recurrent and refractory strictures. If such a selection bias has occurred, we doubt the results of this study would have been substantially impacted for 2 reasons. First, patients who were lost due to missing follow-up were missing completely at random when assessed for baseline characteristics. Second, of all included patients, 14 (16.1%) had only 1 or 2 dilations. And there was no difference in outcome between these 14 patients and those with more than 3 dilations. We suspect a higher proportion of patients with LBESs have recurrent and refractory strictures. To our knowledge, this is the first study addressing the importance of stricture length in LBESs. Strictures of 20 mm or longer had substantially worse outcomes compared to those reported in the literature for shorter complex benign strictures. For most patients with LBES, dysphagia did not improve or even worsened during follow-up, and a substantial proportion required gastrostomy. Long-term outcomes did not appear to differ between different stricture lengths; a prospective study to define the natural history of LBES would aid future shared decision-making, weighing individual benefits against risks of treatment regimens for these patients. Notes Presented at Digestive Diseases Week 2016, May 21–24, 2016, San Diego, California; American College of Gastroenterology 2016 Annual Scientific Meeting, October 14–19, 2016, Las Vegas, Nevada; and the 24th United European Gastroenterology Week October 15–19, 2016, Vienna, Austria. Portions of this manuscript have been published in abstract form: Simons-Linares R, Bartel M J, Patel K, Brahmbhatt B, Bhurwal A, Woodward T A. Tu1231: The long-term outcome of long complex benign esophageal strictures. Gastrointest Endosc 2016; 83: AB1–AB694. Conflict of interest: Dr Wallace reports consulting income from Olympus and grant support from Boston Scientific, Olympus, Medtronic, and Cosmo pharmaceuticals. None of the other authors have conflicts of interest to disclose. Source and role of funding: None. References 1 Kochman M L, McClave S A, Boyce H W. The refractory and the recurrent esophageal stricture: a definition. Gastrointest Endosc  2005; 62: 474– 5. Google Scholar CrossRef Search ADS PubMed  2 Lew R J, Kochman M L. A review of endoscopic methods of esophageal dilation. J Clin Gastroenterol  2002; 35: 117– 26. Google Scholar CrossRef Search ADS PubMed  3 Ikeya T, Ohwada S, Ogawa T et al.   Endoscopic balloon dilation for benign esophageal anastomotic stricture: factors influencing its effectiveness. Hepatogastroenterology  1999; 46: 959– 66. Google Scholar PubMed  4 Chiu Y C, Hsu C C, Chiu KW et al.   Factors influencing clinical applications of endoscopic balloon dilation for benign esophageal strictures. Endoscopy  2004; 36: 595– 600. Google Scholar CrossRef Search ADS PubMed  5 Qureshi S, Ghazanfar S, Leghari A, Tariq F, Niaz S K, Quraishy M S. Benign esophageal strictures: behaviour, pattern and response to dilatation. J Pak Med Assoc  2010; 60: 656– 60. Google Scholar PubMed  6 Hordijk M L, Siersema P D, Tilanus H W, Kuipers E J. Electrocautery therapy for refractory anastomotic strictures of the esophagus. Gastrointest Endosc  2006; 63: 157– 63. Google Scholar CrossRef Search ADS PubMed  7 Kochhar R, Ray J D, Sriram P V, Kumar S, Singh K. Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures. Gastrointest Endosc  1999; 49: 509– 13. Google Scholar CrossRef Search ADS PubMed  8 Kochhar R, Makharia GK. Usefulness of intralesional triamcinolone in treatment of benign esophageal strictures. Gastrointest Endosc  2002; 56: 829– 34. Google Scholar CrossRef Search ADS PubMed  9 Kim J H, Song H Y, Choi E K, Kim K R, Shin J H, Lim J O. Temporary metallic stent placement in the treatment of refractory benign esophageal strictures: results and factors associated with outcome in 55 patients. Eur Radiol  2009; 19: 384– 90. Google Scholar CrossRef Search ADS PubMed  10 Repici A, Hassan C, Sharma P, Conio M, Siersema P. Systematic review: the role of Self-Expanding plastic stents for benign oesophageal strictures. Aliment Pharmacol Ther  2010; 31: 1268– 75. Google Scholar CrossRef Search ADS PubMed  11 Atkinson M. Diseases of the alimentary system. Dysphagia Br Med J  1977; 1: 91– 3. Google Scholar PubMed  12 de Wijkerslooth L R, Vleggaar F P, Siersema P D. Endoscopic management of difficult or recurrent esophageal strictures. Am J Gastroenterol  2011; 106: 2080– 91. Google Scholar CrossRef Search ADS PubMed  13 Bartel M J, Seeger K, Jeffers K et al.   Topical Mitomycin C application in the treatment of refractory benign esophageal strictures in adults and comprehensive literature review. Dig Liver Dis  2016; 48: 1058– 65. Google Scholar CrossRef Search ADS PubMed  14 Hirdes M M, van Hooft J E, Koornstra J J et al.   Endoscopic corticosteroid injections do not reduce dysphagia after endoscopic dilation therapy in patients with benign esophagogastric anastomotic strictures. Clin Gastroenterol Hepatol  2013; 11: 795– 801.e1. Google Scholar CrossRef Search ADS PubMed  15 Ramage J I Jr., Rumalla A, Baron T H et al.   A prospective, randomized, double-blind, placebo-controlled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures. Am J Gastroenterol  2005; 100: 2419– 25. Google Scholar CrossRef Search ADS PubMed  16 Hordijk M L, van Hooft J E, Hansen B E, Fockens P, Kuipers E J. A randomized comparison of electrocautery incision with Savary bougienage for relief of anastomotic gastroesophageal strictures. Gastrointest Endosc  2009; 70: 849– 55. Google Scholar CrossRef Search ADS PubMed  17 Simmons D T, Baron T H. Electroincision of refractory esophagogastric anastomotic strictures. Dis Esophagus  2006; 19: 410– 4. Google Scholar CrossRef Search ADS PubMed  18 Grooteman K V, Wong Kee Song L M, Vleggaar F P, Siersema P D, Baron T H. Non-adherence to the rule of 3 does not increase the risk of adverse events in esophageal dilation. Gastrointest Endosc  2017; 85: 332– 337.e1. Google Scholar CrossRef Search ADS PubMed  19 Richter J E. Rule of three for esophageal dilation: like the tortoise versus the rabbit, low and slow is our friend and our patients' win. Gastrointest Endosc  2017; 85: 338– 9. Google Scholar CrossRef Search ADS PubMed  20 Siersema P D, de Wijkerslooth L R. Dilation of refractory benign esophageal strictures. Gastrointest Endosc  2009; 70: 1000– 12. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Diseases of the EsophagusOxford University Press

Published: May 1, 2018

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