Long-term Efficacy of Combined Treatment in Patients with Idiopathic Achalasia.

BACKGROUND Several treatment strategies are available to treat achalasia. Although combined therapy has been used for several years, there are limited data on long-term outcomes. We aimed to determine its long-term efficacy in patients who were resistant or those with rapid relapse. METHODS In this prospective study, we reviewed the records of 1100 patients with achalasia, who were candidates for pneumatic balloon dilatation (PBD) in our center from 1996 to 2018. We enrolled 197 patients resistant to initial treatment or with rapid relapse of symptoms after three sessions of PBD. Clinical evaluation and time barium esophagogram (TBE) were done before treatment, a month afterward, and when clinical symptoms increased in order to confirm relapse, and at the end of follow-up. RESULTS A total of 168 patients accepted combined therapy. The mean duration of follow-up was 9.04 years. Achalasia symptom score (ASS) dropped from 10.82 to 3.62 a month after treatment and was 3.09 at the end of the follow-up (p = 0.0001 and 0.001). TBE had a decrease in mean height of barium one month after treatment (9.23 vs. 5.10, p = 0.001), and this reduction persisted until the end of follow-up (3.39, p = 0.001). Vantrappen score at the end of the follow-up showed 56 patients in excellent, 51 in good, 33 in moderate, and 14 in poor condition (89% acceptable response rate). CONCLUSION Our results showed the long-term efficacy of combined treatment in patients with achalasia who otherwise had to undergo a high-risk and costly procedure, which makes it a safe and effective alternative for myotomy.

Identification of differentially expressed microRNAs in primary esophageal achalasia by next-generation sequencing.

Molecular knowledge regarding the primary esophageal achalasia is essential for the early diagnosis and treatment of this neurodegenerative motility disorder. Therefore, there is a need to find the main microRNAs (miRNAs) contributing to the mechanisms of achalasia. This study was conducted to determine some patterns of deregulated miRNAs in achalasia. This case-control study was performed on 52 patients with achalasia and 50 nonachalasia controls. The miRNA expression profiling was conducted on the esophageal tissue samples using the next-generation sequencing (NGS). Differential expression of miRNAs was analyzed by the edgeR software. The selected dysregulated miRNAs were additionally confirmed using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fifteen miRNAs were identified that were significantly altered in the tissues of the patients with achalasia. Among them, three miRNAs including miR-133a-5p, miR-143-3p, and miR-6507-5p were upregulated. Also, six miRNAs including miR-215-5p, miR-216a-5p, miR-216b-5p, miR-217, miR-7641 and miR-194-5p were downregulated significantly. The predicted targets for the dysregulated miRNAs showed significant disease-associated pathways like neuronal cell apoptosis, neuromuscular balance, nerve growth factor signaling, and immune response regulation. Further analysis using qRT-PCR showed significant down-regulation of hsa-miR-217 (p-value = 0.004) in achalasia tissue. Our results may serve as a basis for more future functional studies to investigate the role of candidate miRNAs in the etiology of achalasia and their application in the diagnosis and probably treatment of the disease.

Safety and Efficacy of Graded Gradual Pneumatic Balloon Dilation in Idiopathic Achalasia Patients: A 24-Year Single-Center Experience.

BACKGROUND: Pneumatic balloon dilation (PBD) is a first line treatment for idiopathic achalasia. Here we report the safety and efficacy of graded gradual PBD on short and long-term follow-up. METHODS: We evaluated 1370 idiopathic achalasia patients over a period of 24 years (1994-2018), prospectively. 216 patients did not undergo PBD due to comorbid diseases. Ultimately, 1092 achalasia patients were enrolled. All patients underwent graded gradual PBD, with repeat dilation if symptoms relapsed. Response to treatment was evaluated by Vantrappen scoring system. RESULTS: Of 1092 achalasia patients, 937 patients were treated by PBD and 155 patients were treated by combined therapy (PBD 1 month after Botulinum toxin injection). In short-term follow-up, 728 of 1092 patients underwent one PBD and 77.3% of them had excellent or good response (responders), 163 patients (58.6%) who underwent two PBDs were responders, and 44 (51.2%) patients who underwent three PBDs were responders. Overall, 2193 balloon dilations were performed on 1092 patients (mean 2 PBDs/patient). Of 786 patients with long-term follow-up, 259 patients had excellent or good response with one PBD. The responders with two, three, and four or more dilations were 149, 67, and 67, respectively. The overall response rate was 69%. No any serious complications were noted by using the graded gradual method. CONCLUSION: Our results show that graded gradual PBD is a safe and effective method for treatment of achalasia patients, and achieves sufficient short and long-term symptomatic remission with high cumulative success rate.

Comparison of Treatment Response in Different Types of Achalasia: A Long-Term Study.

BACKGROUND Three manometric patterns are seen in high-resolution manometry (HRM). Response to treatment has been reported to be different in these subtypes. We aimed to investigate the frequency and response to treatment in subtypes of achalasia. METHODS 306 patients between 15 to 60 years old, naïve to treatment with idiopathic achalasia (IA) were evaluated prospectively in a cohort study for 8 years. The patients were treated with pneumatic balloon dilation (PBD), and evaluated before and one month after PBD with Achalasia Symptom Score (ASS) and timed barium esophagogram (TBE) and then every 6 months with ASS. The primary study outcome was defined as a reduction in ASS (equal to or less than 4) and a reduction greater than 80% in the volume of barium in TBE at 1 month after PBD compared with baseline values. RESULTS According to HRM, 57 were classified as type I (18.62%), 223 as type II (72.9%), and 26 as type III (8.5%). The mean lower esophageal sphincter (LES) residual pressures before treatment were 34.05 ± 31.55, 32.99 ± 17.90, and 37.47 ± 14.07 mmHg in types I, II, and III, respectively (p = 0.18). The mean ASS values before treatment were 12.23, 11.50, and 11.50, for types I, II, and III, respectively (p = 0.29). The ASS dropped to 2.50 in type I, 2.40 in type II, and 2.12 in type III at 1 month after treatment (p = 0.83). Eventually, at the end of follow-up, 24 patients with type I (83%), 82 patients with type II (67%), and five patients with type III (83%) showed sustained good responses (p = 0.528). CONCLUSION Manometric subtypes of achalasia did not have an important role in clinical success in the long term. Achalasia has no definite cure, but with current treatment modalities, palliation of symptoms is possible in over 90% of patients.

Is There Any Evidence for a Viral Cause in Achalasia?

BACKGROUND Achalasia, as an incurable disease is defined by the lack of normal esophageal peristalsis and loss of lower esophageal sphincter relaxation due to impaired myenteric neural plexus. The exact cause of myenteric neural cells degeneration in achalasia is still unknown. One hypothesis is that certain neurotropic viruses and autoimmune factors cause the inflammatory response in myenteric network, which consequently destroy neural cells. This study was designed to find the evidence of viral causes of achalasia. METHODS In this case-control study, 52 patients with achalasia and 50 controls referred to Shariati Hospital, were evaluated for the genome of neurotropic viruses, HPV, and adenovirus by polymerase chain reaction (PCR) and reverse transcription (RT) PCR techniques. RESULTS Genome assessment of neurotropic DNA viruses turned out negative in the patients, however, the genome of HSV-1 (Herpes simplex virus) was found in tissues of six controls. No neurotropic RNA viruses were observed in the tissue samples and whole blood of both the patients and controls. Among non-neurotropic viruses, adenovirus genome was positive in tissues of two out of 52 patients and three out of 50 controls. In addition, one out of 52 patients and two out of 50 controls were positive for HPV infection in tissues. CONCLUSION We could not detect any significant relationship between achalasia and HPV, adenovirus, and neurotropic viruses in the cases. Nevertheless, it does not exclude the hypothesis of either an alternate viral species or resolved viral infection as the etiology of achalasia.

Assessment of Pneumatic Balloon Dilation in Patients with Symptomatic Relapse after Failed Heller Myotomy: A Single Center Experience.

UNLABELLED: BACKGROUND Although Heller myotomy is one of the most effective treatments for achalasia, it may be associated with early or late symptom relapse in some patients. Therefore, additional treatment is required to achieve better control of symptoms. AIM: To evaluate the safety and efficacy of pneumatic balloon dilation (PBD) in patients with symptom relapse after Heller myotomy. METHODS Thirty six post-myotomy patients were evaluated from 1993 to 2013. Six patients were excluded from the analysis because of comorbid diseases or epiphrenic diverticula. Thirty patients were treated with PBD. Primary outcome was defined as a decrease in symptom score to 4 or less and a reduction greater than 80% from the baseline in the volume of barium in timed barium esophagogram in 6 weeks. Achalasia symptom score (ASS) was assessed at 1.5, 3, 6, and 12 months after treatment and then every six months in all patients and PBD was repeated in case of symptom relapse (ASS>4). RESULTS The mean age of the patients was 45.5±13.9 years (range: 21-73). Primary outcome was observed in 25 patients (83%). The mean ASS of the patients dropped from 7.8 before treatment to 1.3±2.0 at 1.5 months after treatment (p=0.0001). The mean volume and height of barium decreased from 43.1±33.4 and 7.1±4.7 to 6.0±17.1 and 1.1±2.2, respectively (p=0.003, p=0.003). The mean duration of follow-up was 11.8±6.3 years. At the end of the study, 21 patients (70%) reported sustained good response. No major complications such as perforation or gross bleeding were seen. CONCLUSION PBD is an effective and safe treatment option for achalasia in patients with symptom relapse after Heller myotomy.

Ethanolamine oleate versus botulinum toxin in the treatment of idiopathic achalasia.

BACKGROUND: Botulinum toxin (BT) injection reduces lower esophageal sphincter pressure and alleviates symptoms in idiopathic achalasia (IA). Ethanolamine oleate (EO) has also been introduced for the treatment of IA. We compared the long-term efficacy of BT and EO injections in the treatment of IA. METHODS: A total of 189 IA patients were evaluated prospectively, of whom 21 were unwilling to undergo or were poor candidates for pneumatic balloon dilation and Heller myotomy and were enrolled in the study. Eleven patients were treated by BT, and 10 by EO injections. Patients were followed up by achalasia symptom score (ASS), timed barium esophagogram (TBE), and high-resolution manometry at baseline and post-treatment. A good initial response was defined as a decrease in ASS to 4 or less, and a reduction in barium column height and volume in TBE by >50%. RESULTS: All 10 EO group patients and 10 of 11 BT group patients showed a good initial response. Four EO group relapsers and 6 BT group relapsers were managed effectively by re-injections. Mean duration of follow up was 27.38 months. On completion of the study, a sustained good response was seen in 9 and 6 patients in EO and BT groups, respectively (P=0.149). CONCLUSION: This study revealed that BT and EO have comparable efficacy in the treatment of IA. However, the cost of EO is about 2 times lower than BT.