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Systematic Review and Meta-Analysis on the Treatment of Diffuse Esophageal Spasm

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Systematic Review and Meta-Analysis on the Treatment of Diffuse Esophageal Spasm original article Eur Surg (2019) 51:239–245 https://doi.org/10.1007/s10353-019-0574-0 Systematic review and meta-analysis on the treatment of diffuse esophageal spasm Harry Vercoe · Mubashir Mulla · Wyn G. Lewis · Antonio Foliaki · David S. Y. Chan Received: 5 February 2019 / Accepted: 8 February 2019 / Published online: 1 March 2019 © Springer-Verlag GmbH Austria, part of Springer Nature 2019 Summary Keywords Nifedipine · Treatment · Diffuse esophageal Background Diffuse esophageal spasm is a rare motil- spasm · Myotomy · Botulinum toxin ity disorder and although diagnosis has improved over the years, optimal treatment remains controversial. Introduction The aim of this study was to determine the success rates of alternative treatments for diffuse esophageal Diffuse esophageal spasm (DES) is a rare condition spasm. with an annual incidence of 0.2/100,000, occurring Methods MEDLINE, EMBASE, and the Cochrane Li- in some 3–5% of esophageal motility disorder (OMD) brary were searched for studies which reported treat- cases [1, 2]. It is more likely to occur in patients over ment outcomes in patients with diffuse esophageal the age of 50 years and should be considered as a dif- spasm. The primary outcome measure was success ferential diagnosis in elderly patients presenting with rate. Secondary outcome measures were morbidity unexplained esophageal symptoms [3]. Although dys- and mortality. phagia and chest pain are the two most common pre- Results Ten observational studies involving 101 pa- senting symptoms, DES can often resemble gastro- tients (35 male, 66 female, median age 61 years) esophageal reflux disease (GERD) [3]. In keeping with with diffuse esophageal spasm treated with nifedip- its rarity in the general population, such symptom ine (n= 24), botulinum toxin (n= 41), and surgery heterogeneity renders DES a challenging condition to (n= 46) were analyzed. At a median follow-up of diagnose, commonly resulting in diagnostic delay [3], 8 months, the overall success rates for nifedipine, and esophageal manometry represents the diagnos- botulinum toxin, and surgery were 42.74% (95% tic investigation of choice [4, 5]. However, this is not c.i. [42.68–42.79], p< 0.00001), 74.39% (95% c.i. a first-line investigation but indicated after routine in- [74.27–74.52], p< 0.00001), and 95.74% (95% c.i. vestigations have ruled out other causes of chest and [95.69–95.80], p< 0.00001), respectively. Morbidity esophageal symptoms [4–6]. DES is defined mano- after surgery was 2% and no operative deaths were metrically by the distal latency (DL), which refers to reported. the frequency of premature contractions [7]. If prema- Conclusion Surgery appears to be safe and the most ture contractions occur in >20% of swallows and the successful treatment. The less invasive medical and integrated relaxation pressure is normal, then a diag- botulinum toxin therapies provide short-term symp- nosisofDEScanbemade[7]. tom relief. With the introduction of the Chicago Classification in 2008 and improvements in investigations, diagnos- tic certainty has improved [8]. Yet, although treatment H. Vercoe options have developed over the past 5 years, contro- Cardiff University, Heath Park, Cardiff, CF14 4XN, Wales, UK versies remain regarding the optimum treatment [9, 10]. The aim of this study was to determine the suc- M. Mulla, MD · W. G. Lewis, FRCS · A. Foliaki, FRCS · cess rates of different treatment options for patients D. S. Y. Chan, FRCS () University Hospital of Wales, Heath Park, Cardiff, CF14 with DES. The primary outcome measure was the rel- 4XN, Wales, UK ative treatment success rate and secondary outcome [email protected] K Treating diffuse oesophageal spasm 239 original article measures were treatment-related morbidity and mor- mined using the Newcastle–Ottawa scale, which ex- tality. amines patient selection methods, comparability of study groups, and assessment of outcome. A score of Materials and methods at least six stars from a maximum of nine was consid- ered to indicate higher quality. Data source and search strategy Data synthesis and statistical analysis A systematic review of current published literature was performed in accordance with the Meta-Analysis The meta-analysis was performed in line with the of Observational Studies and Epidemiology (MOOSE) recommendations from the Cochrane Collaboration and Preferred Reporting Items for Systematic Review and PRISMA guidelines using Review Manager 5.3 and Meta-Analyses (PRISMA) guidelines. MEDLINE, (The Nordic Cochrane Centre, The Cochrane Col- EMBASE, the Cochrane Database of Systematic Re- laboration, Copenhagen, Denmark). Meta-analysis views and the Cochrane Controlled Trials Register, was used to pool study estimates of the outcome Cochrane Library, were the databases selected to measures as detailed above. The pooled estimated carry out the systematic search. A sensitive search outcomes were calculated using generic inverse vari- strategy that combined the exploded thesaurus term ance random effects meta-analysis with standardized for diffuse esophageal spasm or free-text terms in the mean differences and 95% confidence intervals (c.i.) title or abstract for “diffuse [o]esophageal spasm*” quoted. Where results showed that there was 0% or was developed. A preliminary literature search had 100% success, a success rate of 0.01 or 0.99 was used been performed to identify what treatment options in place of 0 or 1, respectively, in order to obtain for DES had been investigated in the literature to date. an estimate of the overall success rate using Review The options found were included through exploded Manager 5.3. thesaurus terms or free-text terms in the search. The results were limited to human trials published in En- Results glish language. No date limit was set to include as many trials as possible. The literature search identified 179 citations through MEDLINE and 531 citations through EMBASE. There Study selection were no results in the Cochrane Database of Sys- tematic Reviews and the Cochrane Controlled Trials Inclusion criteria: Studies reporting treatment out- Register only had 13 results. After reviewing titles comes in patients with DES were included. and abstracts and removing duplications, 96 articles Exclusion criteria: For meta-analysis of data, were identified as being relevant. Of these, 10 studies a given treatment required two or more studies. fulfilled the inclusion criteria and were included in Therefore, if only one study could be found on the the meta-analysis ([11–20]; Fig. 1). Three focused on given treatment, it was disregarded. Reviews and case surgery [11–13], three focused on botulinum toxin reports were excluded. [14–16], and four looked at the effect of nifedipine [17–20] as a treatment option for DES. Data extraction Study characteristics Data Extraction and quality assessment data was ex- tracted by H. Vercoe, M. Mulla, D. Chan using an In total, 101 patients with DES were included in the agreed protocol and any discrepancies were discussed meta-analysis, of whom 24 were treated with nifedip- with all authors to reach a consensus. The following ine, 41 with botulinum toxin, and 46 were treated sur- information were extracted from each study: treat- gically. The median age was 37, 63, and 66 years in ment option assessed, first author, article title, year the medical, botulinum toxin, and surgery groups re- of publication, country of origin, total number of pa- spectively. The median duration of follow-up was 1.5, tients, number of DES patients, age, gender, present- 12, and 24 months in the respective groups. The de- ing symptoms, prior treatment, mean follow-up, def- mographic data and study characteristics are summa- inition of success, number of successes, duration of rized in Table 1. success, number of adverse events, morbidity, mortal- ity. Authors were not contacted for incomplete data. Characteristics of included studies The primary outcome measure was the rate of success for a given treatment. The definition of success varied All selected medical treatment studies examined the depending on the outcome measures that were as- effectiveness of nifedipine. However, the objectives sessed in different papers. Secondary outcome mea- and methods differed between studies. For example, sures included rate of adverse events, morbidity, and Davies et al. reported the long-term effects of nifedip- mortality, which were noted but not included in the ine on DES, whereas Blackwell et al. reported the ef- meta-analysis calculations. Study quality was deter- fectiveness of acute administration on symptom relief. 240 Treating diffuse oesophageal spasm K original article Fig. 1 Identifcation pro- cess for eligible studies Records identified through database Records identified through other searching sources (n=710) (n= 23) Records after duplicates removed (n=679) Records screened by title/abstract (n=619) Records excluded (n=586) Full text assessed for eligibility (n=93) Records excluded (n=83) 13 not meeting inclusion criteria Studies included in meta-analysis (n=10) Table 1 Characteristics of studies included in the meta-analysis Author Year Country Total Age~ Male (n) F/U~ NO^ Success definition Number of successes Medical—nifedipine Blackwell [17] 1981 Scotland 6 36 4 – 5 Reduction >2mmHg in LES pressure 5 Davies [18] 1987 UK 8 39 4 1.5 6 Significantly reduced pain severity and 0 frequency score Nasrallah [19] 1985 USA 4 – – 1 6 Symptom improvement score >7 (0–10) 4 Thomas [20] 1986 USA 6 – 3 3 6 >50% reduction in symptom score, on 5 scale 0–10 Botulinum toxin Miller [14] 2002 USA 17 61 4 24 6 ≥50% reduction in chest pain score 13 Storr [15] 2001 Germany 9 71 3 6 7 Total symptom score of ≤3 8 Vanuytsel [16] 2013 Belgium 15 63 4 12 8 Modified Vantrappen criteria for achala- 7 sia Surgery Eypasch [11] 1992 USA 17 – – 24 6 Would patient have operation again? 15 Khashab [12] 2015 USA 9 71 6 8 7 Eckardt score of 0–3 9 Leconte [13] 2007 France 20 62 7 50 7 Eckardt score of 0 or 1 16 F/U Follow-up, NO Newcastle-Ottawa score, LES lower esophageal sphincter K Treating diffuse oesophageal spasm 241 original article Fig.
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