Table 2.
Review of experiences using BT for the treatment of esophageal achalasia.
| Authors | Description | Patients | Results/Conclusions |
|---|---|---|---|
| Pasricha et al., 1995 [5] | BT vs. Placebo | 21 | 67% improvement at 6 weeks |
| Annese et al., 1996 [55] | BT vs. placebo vs. PBD | 16 | 100% improvement at 1 month. BT is as effective as pneumatic dilatation |
| Fiorini et al., 1996 [56] | BT vs. Placebo | 13 | 72% improvement at 3 month |
| Pasricha et al., 1996 [57] | BT | 31 | 60% (82% of those aged > 50) improvement at 3 month |
| Fishman et al., 1996 [58] | BT | 65 | 60 idiopatic cases: BT treatment improved symptoms of dysphagia, Chet pain and regurgitation in the majority of patients. 5 secondary cases: There was no response to BT in 4 patients. Patients, who respond to a first BT injection but relapse, may respond to a second treatment |
| Cuilliere et al., 1997 [59] | BT | 55 | 60% improvement at 6 month |
| Kolbasnik et al., 1999 [60] | BT | 30 | Symptomatic improvement for >3 month was seen in 77% of patient. 7 patient had a sustained response after a single injection; 16 relapsed and required re-treatment |
| Annese et al., 1999 [61] | Botox vs. Dysport | 78 | Comparable efficacy in esophageal achalasia after up to 6 month after treatment |
| Muehldorfer et al., 1999 [62] | BT vs. PBD | 24 | The two treatment had equal initial success rate (dilatation 83%, BT 75%). In the long term the efficacy of BT injection was statistically significantly and shorter than that of balloon dilatation |
| Greaves et al., 1999 [63] | BT | 11 | The relapse rate was 73% within 2 years from treatment. There were a beneficial effect on dysphagia, no improvement in chest pain or regurgitation scores, and no reduction of mean LES pressure were improved at 6 weeks |
| Wehrmann et al., 1999 [64] | BT in high risk patients | 20 | 80% were improved at 6 weeks. Mean cardia diameter was increased from 2.1 mm to 3.2 mm. The patients who initially had a symptomatic relapse after an average of 5 months. BT re-injections were efficacious |
| Hurwitz et al., 2000 [65] | BT in children | 23 | The mean duration of effect in 19 responders was 4.2 months. 50% of the patients required an additional procedure (PD, surgery) on average 7 months after the first treatment |
| Annese et al., 2000 [66] | BT dose raging study | 118 | 82% of the patients were responders at 1 month. No dose related effect was observed. Vigorous achalasia was the main determinant of BT response |
| Mikaeli et al., 2001 [67] | BT vs. PBD | 40 | Cumulative 12-month remission rate was significantly higher after a single PD (53%) compared to a single BT injection (15%, p < 0.01). The 12-month estimated adjusted hazard for relapse and need for retreatment for BT group was 2.69 times that of the PD group |
| Allescher et al., 2001 [68] | BT vs. PBD | 37 | After 24 months a single PD was superior to a single BT injection, and after 48 months all patients treated for BT injection had experienced a symptomatic relapse |
| Ghoshal et al., 2001 [69] | BT vs. PBD | 17 | Both therapies resulted in a significant reduction in LES pressure |
| Zarate et al., 2002 [70] | BT | 17 | The effect of BT injection wanes with time in elderly patients, necessitating repeated injections to keep the patients symptoms free |
| D’Onofrio et al., 2002 [71] | BT | 37 | Of the 35 patients followed, 12 had a relapse and were treated; 4 out of 12 did not respond after treatment. One or two BT injections result in a clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; patients over 50 years showed better benefit than younger patients |
| Neubrand et al., 2002 [72] | BT | 25 | Good results after 2.5 years of median follow up in 9 of 25 patient that were significantly older than 14 patients for whom BT treatment was unsuccessful |
| Brant et al., 2003 [73] | BT in Chagas’ disease | 24 | Over a period of 6 month, clinical improvement of dysphagia was statistically significant (p < 0.001) in patients receiving BT when compared with the placebo. Esophageal emptying time in BT group was significantly lower than in the placebo (p = 0.04) after 90 days |
| Bansal et al., 2003 [74] | BT vs. PBD | 32 | After 12 month follow up 16 of 18 patients of PBD were in clinical remission despite 6 of 16 of BT group |
| Martinek et al., 2003 [75] | BT vs. PBD | 41 | 16 patients had BT injection from the antegrade angle only (group A), 15 both from antegrade than retrograde (group B) and 10 had subsequent PD (group C). 93% had an immediate clinical response after 1 month ad 49 were in remission after 22 months. Better responders were older and with lower LES pressure. Patients in group C had better results at 1 and 2 year |
| Vela et al., 2004 [76] | PBD vs. HM vs. BT | 232 | 111 patients underwent PBD, 72 HM and 39 elderly patients BT injection. 48 patients had already surgical treatment and underwent to PBD or redo-HM. PBD and HM are the best treatments for untreated achalasia and are less successful after surgery. BT group needed repeated injections and their symptoms improving lasted for a mean period of 6.2 months |
| PBD vs. HM in patient with prior surgery | |||
| Zaninotto et al., 2004 [77] | BT vs. HM | 80 | After 6 months similar results were reported in the 2 groups of 40 patients, but after 2 years 87.5% of patients of surgical groups were symptoms free vs. 34% of BT group (p < 0.05) |
| Mikaeli et al., 2004 [78] | BT + PBD vs. PBD | 24 | BT + PBD (case-group) had a significant higher cumulative remission rate compared to control (PBD) group (24.6 vs. 12.6 months P < 0.01) and a significant reduction in symptom-score (76% vs. 53% P < 0.001). Control group needed a 35 mm PBD vs. 30 mm of case group |
| Dughera et al., 2005 [79] | BT elderly | 12 | After 12 months of follow-up, up to 70% of patients were considered responders. They underwent 2 BT injection (time 0 and after 1 month). Average age 86 y.o. ASA 3 or 4 |
| Bassotti et al., 2006 [80] | BT elderly | 33 | Patients underwent 2 BT injection (time 0 and after 1 month). 78% were considered responders after 1 year and 54% after 2 years. No relationship was found between baseline LES pressure and symptoms score |
| Mikaeli et al., 2006 [81] | BT + PBD vs. PBD | 54 | 77% of patients of BT + PBD group were in remission after 1 year vs. 62% of PBD group and showed a significant reduction in barium volume at the various times intervals post-treatment |
| Zhu et al., 2009 [82] | BT vs. PBD vs. BT + PBD | 90 | LES pressure and symptom score in group C (BT + PBD) were significantly lower compared with those in group A (BT) or group B (PBD) (p < 0.05). At 2 years after treatment, the response rate in group C remained 56.67% vs. 35.71% (group B) and 13.79% (group A) (p < 0.05) |
| Kroupa et al., 2010 [83] | BT + PBD vs. PBD | 91 | The mean duration of follow-up was 48 months (12–96 months). 41 of 51 patients were followed up more than 2 years. Effect of therapy lasted in 75% (31/41) of them. The cumulative 5 years remission rate in combined treated patients was higher than in controls bu not statistically significant. (p = 0.07). Injection of BT followed by PD seems to be effective for long-term result but the combined therapy is not significantly superior to PD alone |
| Gutschow et al., 2010 [84] | BT vs. PBD vs. PBD-HM vs. HM | 41 | Patients of BT group (n = 7) had the lower mean LES pressure (18.1 mm Hg) and higher recurrence rate (71.4%) compared to patients of PBD group (n = 16, 34.8 mm Hg—50%), PBD-HM group (n = 14, 22.2 mm Hg—35.7%) and HM group (n = 6, 36.4 mm Hg—16.7%) |
| Bakhshipour et al., 2010 [85] | BT + PBD vs. PBD | 34 | Patient of study-group already underwent two initial PBD with a low response. They were randomized to receive another PBD or BT injection and PBD by four weeks interval. BT + PBD group had higher remission rate at 1, 6 and 12 months compared to PBD group (87.5% vs. 67.1%, 87.5% vs. 61.1%, 87.5% vs. 55.5%, respectively). Difference was not statistically significant |
| Porter et al., 2011 [86] | BT | 36 | Response lasted a mean of 12.8 months and symptom relief for > 6 months was seen in 58.3% of patients. Chest pain, younger age and contraction amplitudes >180 mmHg independently predicted <6 months relief (p < 0.05 for each) |
| Ciulla et al., 2013 [87] | BT | 68 | 36 patients underwent echo-guided BT injection had complete relief of obstruction compared to 32 patients who underwent blind treatment. |
| Cai et al., 2013 [88] | BT vs. SEMS | 110 | Improvements in global symptom, dysphagia scores and in LES pressure were significantly more marked in the SEMS group (n = 59) than in the BT group (n = 51). Remission rate in the SEMS group was statistically significantly higher than that in the BT group at 12 and 36 months [81.28 vs. 64.58 (p < 0.05) and 49.1 vs. 4.2 (p < 0.01)]. No side effects were reported in BT group vs. 26 in SEMS group |
| Jung et al., 2014 [53] | BT vs. PBD | 37 | A significant difference was observed in the mean remission duration between the BT injection (n = 25) and PBD (n = 12) (13 months vs. 29 months). Independent factors predicting long-term remission included treatment type and the difference in the initial LES pressure |
| Marjoux et al., 2014 [48] | BT | 45 | 22 patients had achalasia, 8 jackhammer esophagus, 7 distal esophageal spasm, 5 esophagogastric junction outflow obstruction, 1 nutcracker esophagus, and 2 unclassified cases. 71% were significantly improved after 2 months and 57% remained satisfied for more than 6 months. No clear difference was observed in terms of response according to manometric diagnosis. Type 3 achalasia had the worst outcome with none of these patients responded to the endoscopic BT injection |
BT, Botulinum toxin; HM, Heller myotomy; LES, lower esophageal sphincter; PBD, pneumatic balloon dilatation; PD, pneumatic dilatation; SEMS, self-expanding metal stent.