今日の臨床サポート

食道アカラシア

著者: 保坂浩子1) 群馬大学医学部附属病院 消化器・肝臓内科

著者: 草野元康2) 群馬大学医学部附属病院 光学医療診療部

監修: 木下芳一 兵庫県立姫路循環器病センター/製鉄記念広畑病院

著者校正/監修レビュー済:2021/10/27
参考ガイドライン:
  1. 日本食道学会:食道アカラシア取扱い規約 第4版
  1. 日本消化管学会:食道運動障害診療指針(2016)
  1. 日本消化器内視鏡学会:POEM診療ガイドライン(2018)
患者向け説明資料

概要・推奨   

  1. 偽性アカラシア(悪性腫瘍によるもの)は全食道アカラシア症例のうち3.6%、60歳以上の食道アカラシア症例のうちの9%を占めるため、食道アカラシアを疑った症例では鑑別が必要である(推奨度2)
  1. 硝酸薬やCa拮抗薬はLES圧を容量依存性に低下させ、症状の改善に寄与する。食道アカラシア患者に対する症状改善の奏効率は硝酸薬、Ca拮抗薬ともに5~8割である(推奨度2)
  1. 内視鏡的バルーン拡張術の治療効果について24のuncontrolled studyを評価したreviewでは、奏効率は78%と高く、また食道穿孔の発生率は1.9%と低く、有効性、安全性ともに高い治療である(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
保坂浩子 : 特に申告事項無し[2021年]
草野元康 : 特に申告事項無し[2021年]
監修:木下芳一 : 講演料(アストラゼネカ,武田,大塚,第一三共)[2021年]

改訂のポイント:
  1. 定期レビューを行い、主に治療について加筆修正を行った。
  1. 近年では経口内視鏡的筋層切開術が主要な治療法となり、日本消化器内視鏡学会より、POEM診療ガイドラインが発表された。
  1. 治療薬として長年使用されてきたニフェジピンのカプセル製剤が販売中止となり製剤の在庫がなくなり次第、処方ができなくなる。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 食道アカラシアは、下部食道括約部(lower esophageal sphincter、LES)の弛緩不全と、食道体部の正常蠕動波の消失を特徴とする一次性食道運動障害である。
  1. 嚥下障害と食道からの逆流を主症状とし、慢性進行性の疾患である。
  1. 小児から高齢者まで幅広い年齢層で発症し、男女差はなく、発症頻度は年間人口10万人あたりに1例程度とまれな疾患である。
  1. LESの組織学的研究では、Auerbach神経叢に炎症性細胞浸潤や線維化が認められ、神経節細胞の消失や神経線維の変性が認められることが報告されている。
  1. それらの原因はいまだに不明であるが、遺伝的素因、退化現象、自己免疫説、感染因子などが提唱されている[1]
問診・診察のポイント  
  1. つかえ感の詳細

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文献 

著者: P J Kahrilas, S M Kishk, J F Helm, W J Dodds, J M Harig, W J Hogan
雑誌名: Am J Med. 1987 Mar;82(3):439-46.
Abstract/Text Malignancies involving the gastric cardia or distal esophagus can result in a clinical syndrome termed pseudoachalasisa that mimics idiopathic achalasia. If not promptly recognized, pseudoachalasia can result in inappropriate pneumatic dilatation of the lower esophageal sphincter segment and delay appropriate treatment of the underlying malignancy. During the past 14 years, six patients with pseudoachalasia and 161 patients with primary idiopathic achalasia were encountered. Pseudoachalasia occurred mainly in the elderly and represented about 9 percent of these patients over 60 years of age with suspected achalasia. Five of the six pseudoachalasia cases were secondary to adenocarcinoma that originated in the gastric fundus, and one was caused by a squamous cell carcinoma of the distal esophagus. Conventional esophageal manometry did not discriminate achalasia from pseudoachalasia. On the other hand, esophagogastroscopy with biopsy resulted in a diagnosis of pseudoachalasia in five of these cases and in 24 of 32 cases reported previously. Ominous endoscopic findings are mucosal ulceration or nodularity, reduced compliance of the esophagogastric junction, or an inability to pass the endoscope into the stomach. Radiographic evaluation, particularly in conjunction with amyl nitrite inhalation, was also useful in discriminating pseudoachalasia from primary achalasia. It is concluded that pseudoachalasia generally mimics idiopathic achalasia imperfectly and can usually be diagnosed prior to surgery by fastidious endoscopic and radiographic examination.

PMID 3548347  Am J Med. 1987 Mar;82(3):439-46.
著者: S Rosenzweig, M Traube
雑誌名: J Clin Gastroenterol. 1989 Apr;11(2):147-53.
Abstract/Text An impression that achalasia remains an elusive diagnosis led us to review our recent experience. From August 1, 1985 to March 31, 1987, we saw 25 patients with "previously untreated" achalasia for consultation and/or treatment. Data was extracted from review of their records. Achalasia was the initial diagnosis in only 12 patients. The others were given diagnoses of gastroesophageal reflux (4), presbyesophagus (2), esophageal spasm (2), psychiatric disorders (2), and combination of various disorders (3). In the latter patients, various diagnostic studies were either inappropriately delayed or misinterpreted, so that incorrect diagnoses were given. Errors in diagnosis led to further inappropriate testing and therapies. We conclude that: (a) achalasia remains an elusive diagnosis in current practice, (b) errors in diagnosis are related to delay in obtaining appropriate studies or misinterpretation of such studies, and (c) this delay leads to persistent symptoms and ineffective and/or inappropriate therapies.

PMID 2738356  J Clin Gastroenterol. 1989 Apr;11(2):147-53.
著者: H J Tucker, W J Snape, S Cohen
雑誌名: Ann Intern Med. 1978 Sep;89(3):315-8.
Abstract/Text The clinical and diagnostic features of a secondary type of achalasia of the esophagus are described in seven patients with various types of malignancies. Patients with secondary achalasia presented with dysphagia of short duration and marked weight loss; mean age was 64 years. Esophageal manometry showed features identical to those of idiopathic primary achalasia: aperistalsis, poor lower esophageal sphincter relaxation, and elevated sphincter pressure. Endoscopy and barium swallow showed evidence of a tumor in only two cases. Various types of malignancies may produce a secondary form of achalasia that has diagnostic features identical to those of primary achalasia and is best identified by its clinical presentation.

PMID 686541  Ann Intern Med. 1978 Sep;89(3):315-8.
著者: R W Rozman, E Achkar
雑誌名: Am J Gastroenterol. 1990 Oct;85(10):1327-30.
Abstract/Text Eighteen patients with cancer-induced or secondary achalasia (SA) were compared to 421 patients with idiopathic or primary achalasia (PA). The aim of the study was to detect any differences in clinical presentation between the two groups. Mean age of patients with SA was 57.1 (range 15-78) and 47.1 (range 1-90) in patients with PA (p = 0.02). Three patients with SA were 15, 24, and 36 yr old, respectively. Symptom frequency was comparable in SA versus PA. Mean duration of symptoms in SA was 4.5 months, with 15 of the 18 patients experiencing symptoms for six months or less. Weight loss occurred in 88.2% of patients with SA and 57.3% of patients with PA (p less than 0.05). Cancer was at the gastroesophageal junction in 16 patients, duodenum in one, and breast in one. Endoscopy showed tumor in 12 (67%). The esophagram was suspicious for tumor in only 25%. We conclude that patients with SA are older, more likely to lose weight, and have a short duration of symptoms. However, SA may occur in younger patients, and endoscopy with biopsy is necessary in any newly diagnosed case of achalasia.

PMID 2220723  Am J Gastroenterol. 1990 Oct;85(10):1327-30.
著者: Ines Gockel, Volker F Eckardt, Thomas Schmitt, Theodor Junginger
雑誌名: Scand J Gastroenterol. 2005 Apr;40(4):378-85.
Abstract/Text OBJECTIVE: Pseudoachalasia frequently cannot be distinguished from idiopathic achalasia by manometry, radiologic examination or endoscopy. Mechanisms proposed to explain the clinical features of pseudoachalasia include a circumferential mechanical obstruction of the distal esophagus or a malignant infiltration of inhibitory neurons within the myenteric plexus.
MATERIAL AND METHODS: Between January 1980 and December 2002, the clinical features of 5 patients with pseudoachalasia and 174 patients with primary achalasia, diagnosed in a single center, were compared. A literature analysis of the etiology of pseudoachalasia for the time period 1968 to December 2002 was performed. The search concentrated on the databases and online catalogues PubMed, Web of Science, Cochrane Library and Current Contents Connect.
RESULTS: In our case series, patients with pseudoachalasia reported a shorter duration of symptoms and tended to be older than patients with primary achalasia. Conventional manometry, endoscopy and radiologic examination of the esophagus proved to be of little value in distinguishing between the diseases. In the majority of cases only surgical exploration revealed the underlying cause. A coincidence of primary achalasia and disorders of the gastroesophageal junction was excluded by showing return of peristalsis following treatment. The analysis of the literature showed a total of 264 cases of pseudoachalasia in 122 publications. Most cases of were due to malignant disease (53.9% primary and 14.9% secondary malignancy), followed by benign lesions (12.6%) and sequelae of surgical procedures at the distal esophagus or proximal stomach (11.9%). In rare instances, the disease was an expression of a paraneoplastic process due to distant neuronal involvement rather than to local invasion with destruction of the myenteric plexus (2.6%).
CONCLUSIONS: The diagnosis of pseudoachalasia is difficult to establish by conventional diagnostic measures. The main distinguishing feature of secondary versus primary achalasia is the complete reversal of pathologic motor phenomena following successful therapy of the underlying disorder.

PMID 16028431  Scand J Gastroenterol. 2005 Apr;40(4):378-85.
著者: John E Pandolfino, Monika A Kwiatek, Thomas Nealis, William Bulsiewicz, Jennifer Post, Peter J Kahrilas
雑誌名: Gastroenterology. 2008 Nov;135(5):1526-33. doi: 10.1053/j.gastro.2008.07.022. Epub 2008 Jul 22.
Abstract/Text BACKGROUND & AIMS: Although the diagnosis of achalasia hinges on demonstrating impaired esophagogastric junction (EGJ) relaxation and aperistalsis, 3 distinct patterns of aperistalsis are discernable with high-resolution manometry (HRM). This study aimed to compare the clinical characteristics and treatment response of these 3 subtypes.
METHODS: One thousand clinical HRM studies were reviewed, and 213 patients with impaired EGJ relaxation were identified. These were categorized into 4 groups: achalasia with minimal esophageal pressurization (type I, classic), achalasia with esophageal compression (type II), achalasia with spasm (type III), and functional obstruction with some preserved peristalsis. Clinical and manometric variables including treatment response were compared among the 3 achalasia subtypes. Logistic regression analysis was performed using treatment success as the dichotomous dependent variable controlling for independent manometric and clinical variables.
RESULTS: Ninety-nine patients were newly diagnosed with achalasia (21 type I, 49 type II, 29 type III), and 83 of these had sufficient follow-up to analyze treatment response. Type II patients were significantly more likely to respond to any therapy (BoTox [71%], pneumatic dilation [91%], or Heller myotomy [100%]) than type I (56% overall) or type III (29% overall) patients. Logistic regression analysis found type II to be a predictor of positive treatment response, whereas type III and pretreatment esophageal dilatation were predictive of negative treatment response.
CONCLUSIONS: Achalasia can be categorized into 3 subtypes that are distinct in terms of their responsiveness to medical or surgical therapies. Utilizing these subclassifications would likely strengthen future prospective studies of treatment efficacy in achalasia.

PMID 18722376  Gastroenterology. 2008 Nov;135(5):1526-33. doi: 10.1053・・・
著者: M Gelfond, P Rozen, S Keren, T Gilat
雑誌名: Gut. 1981 Apr;22(4):312-8.
Abstract/Text The effect of a long-acting nitrate, isosorbide dinitrate (ID) 5 mg sublingually, on the lower oesophageal sphincter was tested in 24 patients with achalasia. The drug caused a reduction in LOS pressure in all cases. The mean LOS pressure fell from 46.32.7 mmHg to 15.31.8 mmHg (p less than 0.01). The pressure began to drop after several minutes, reaching its lowest levels after 15 minutes. This measured manometric effect lasted for 60 minutes or more in 10 patients studied. The reported clinic effect lasted for two to three hours, permitting the ingestion of a meal. Twenty-three patients were followed clinically for two to 19 months while receiving the drug three times daily before meals. Nineteen reported a marked to complete relief of dysphagia. Five of these patients had previous pneumatic dilatation, cardiomyotomy, or both, and had recurrence at time of study. Side-effect, mainly headache, were reported in eight patients. In six this was alleviated by substituting oral isosorbide dinitrate, 10 mg. Two patients became refractory to treatment after two to six months. The potential role of long-acting nitrates in the treatment of achalasia has yet to be established.

PMID 7239323  Gut. 1981 Apr;22(4):312-8.
著者: M Bortolotti, G Labò
雑誌名: Gastroenterology. 1981 Jan;80(1):39-44.
Abstract/Text The effect of a new calcium antagonist, nifedipine, which has a spasmolytic activity on smooth muscle cells, was studied on the esophageal function of 20 patients with achalasia of mild and moderate degree. The study was carried out by using constantly perfused catheters and recording the pressure variations at the lower esophageal sphincter, before and after sublingual administration of 10-20 mg of nifedipine. The drug significantly decreased the lower esophageal sphincter pressure for more than 1 h. A clinical trial was also carried out by assessing the improvement of symptoms in achalasia patients taking sublingually a dose of 10-20 mg of nifedipine before each meal. After 6-18 mo of nifedipine therapy these patients underwent a placebo treatment, whereas an additional group of 9 achalasia patients was treated first with placebo followed by nifedipine. The nifedipine treatment gave excellent or good results in a large majority of patients of both groups. The moderate results were only 5 and the poor responses only 3. The clinical improvement induced by nifedipine was statistically significant when compared, not only with the pretreatment clinical state, but also with the results of the placebo treatment. No tachyphylaxis and few side effects were seen either during the manometric recordings or the longest periods of therapy. This study suggests that nifedipine may be advantageously used in the medical treatment of achalasia of mild or moderate degree.

PMID 7450409  Gastroenterology. 1981 Jan;80(1):39-44.
著者: M Gelfond, P Rozen, T Gilat
雑誌名: Gastroenterology. 1982 Nov;83(5):963-9.
Abstract/Text The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.

PMID 6288509  Gastroenterology. 1982 Nov;83(5):963-9.
著者: M Traube, S Dubovik, R C Lange, R W McCallum
雑誌名: Am J Gastroenterol. 1989 Oct;84(10):1259-62.
Abstract/Text Utilizing the rationale that the calcium channel blocker nifedipine decreases lower esophageal sphincter pressure, we performed a double-blind, placebo-controlled, crossover trial of sublingual nifedipine in achalasia, a disorder whose treatment depends on reduction in lower esophageal sphincter pressure. Ten patients participated in this trial, completed diaries, underwent manometric determinations of lower esophageal sphincter pressure, and had testing of esophageal emptying rates by a solid-meal radionuclide method. Nifedipine, titrated to a dose of 10-30 mg before meals, was well tolerated. Compared with placebo, nifedipine significantly reduced the frequency of dysphagia, but some symptoms of dysphagia, regurgitation, or nocturnal cough were still present most days. Nifedipine significantly reduced lower esophageal sphincter pressure by 28%, a value approximately one-half that achieved by successful pneumatic dilatation or myotomy. Esophageal emptying rates, as determined by the radionuclide method, were unchanged by nifedipine. We concluded that 1) nifedipine reduces symptoms of achalasia, but substantial symptoms do remain during such therapy; 2) the suboptimal effect results from the limited, although statistically significant, effect of nifedipine on reduction of lower esophageal sphincter pressure; and 3) although we believe that nifedipine may be recommended as treatment for achalasia in the subset of patients whose overall medical condition places them at high risk for forceful dilatation or surgery, it cannot be recommended as a standard alternative to these other modalities.

PMID 2679048  Am J Gastroenterol. 1989 Oct;84(10):1259-62.
著者: P Rozen, M Gelfond, S Salzman, J Baron, T Gilat
雑誌名: J Clin Gastroenterol. 1982 Feb;4(1):17-22.
Abstract/Text In fifteen patients with achalasia, we measured lower esophageal sphincter pressures before and after 5 mg of sublingual isosorbide dinitrate. The mean pressure fell significantly, from 36.5 to 18.4 mm Hg (P less than 0.01). The effectiveness of this therapy was confirmed by gamma camera measurement of the esophageal emptying time of a radionuclide test meal which was significantly less after the medication (P less 0.05). The emptying time was invariably longer than 10 minutes before therapy, and in 12 of the 15 patients decreased after therapy to 1-8 minutes, corresponding to the clinical response to the drug therapy. The noninvasive radionuclide technique provides a simple way of assessing the results of drug therapy in achalasia.

PMID 7077059  J Clin Gastroenterol. 1982 Feb;4(1):17-22.
著者: G Coccia, M Bortolotti, P Michetti, M Dodero
雑誌名: Gut. 1991 Jun;32(6):604-6.
Abstract/Text A study was carried out in 30 patients affected by a mild or moderate degree of oesophageal achalasia to compare the clinical and manometric effects of sublingual nifedipine and pneumatic dilatation. Sixteen patients were dilated twice with Rider-Moeller dilators and 14 were treated with sublingual nifedipine 10-20 mg 30 minutes before meals. A manometric evaluation was performed before and six months after starting treatment. The clinical evaluation (according to Vantrappen's criteria) was performed every three months for a mean follow up of 21 months. In both groups of patients a significant (p less than 0.001) fall in lower oesophageal sphincter pressure was observed after treatment and excellent or good clinical results were observed in 75% of dilated patients and in 77% of patients treated with nifedipine. One patient could not tolerate nifedipine. No complications were observed after dilatation. It is concluded that longterm treatment with sublingual nifedipine and pneumatic dilatation are equally effective in the treatment of oesophageal achalasia of mild or moderate degree.

PMID 2060867  Gut. 1991 Jun;32(6):604-6.
著者: Marcelo F Vela, Joel E Richter, Farah Khandwala, Eugene H Blackstone, Don Wachsberger, Mark E Baker, Thomas W Rice
雑誌名: Clin Gastroenterol Hepatol. 2006 May;4(5):580-7.
Abstract/Text BACKGROUND & AIMS: Studies comparing long-term success after pneumatic dilatation (PD) and laparoscopic Heller myotomy (HM) are lacking. This study compares long-term outcome of PD (single dilatation and graded approach) and laparoscopic HM and identifies risk factors for treatment failure.
METHODS: A cross-sectional follow-up evaluation of an achalasia cohort treated between 1994 and 2002 was followed-up for a mean of 3.1 years. There was a total of 106 patients treated by graded PD (1-3 dilatations with progressively larger balloons) and 73 patients treated by HM (20 had failed graded PD and crossed over to HM). A symptom assessment (structured telephone interview or clinic visit) was performed and patients were given freedom from alternative therapies to determine treatment outcome. Endoscopy, manometry, and timed barium esophagram were performed to determine the cause of treatment failure.
RESULTS: The success of single PD was defined as freedom from additional PDs: 62% at 6 months and 28% at 6 years (risk factors for failure: younger age, male sex, wider esophagus, and poor emptying on posttreatment timed barium esophagram). Freedom from subsequent PDs increased with each dilatation (graded PD). The success of graded PD and HM, defined as dysphagia/regurgitation less than 3 times/wk or freedom from alternative treatment, was similar: 90% vs 89% at 6 months and 44% vs 57% at 6 years (no risk factors for failure were identified). Causes of symptom recurrence were incompletely treated achalasia (96% after PD vs 64% after HM) and gastroesophageal reflux disease (4% after PD vs 36% after HM).
CONCLUSIONS: No treatment cures achalasia. Short- and long-term success is similar for graded PD and laparoscopic HM. Therapeutic success decreases steadily over time. Achalasia patients need careful long-term follow-up evaluation.

PMID 16630776  Clin Gastroenterol Hepatol. 2006 May;4(5):580-7.
著者: V F Eckardt, C Aignherr, G Bernhard
雑誌名: Gastroenterology. 1992 Dec;103(6):1732-8.
Abstract/Text This prospective study investigates whether the effect of pneumatic dilation in patients with achalasia can be predicted on the basis of patient characteristics, type of treatment, or results of postdilation investigations. Over a period of 10 years, 54 consecutive patients with newly diagnosed achalasia were treated with pneumatic dilation and underwent pretreatment and posttreatment manometric, radiographic, and scintigraphic investigations. They were followed up every 2 years until the fall of 1991. Among the factors evaluated in the initial examination, only young age adversely affected outcome (P < 0.05). With the exception of the diameter of the dilating balloon, the treatment characteristics had a low predictive value. Postdilation lower esophageal sphincter pressure was the single most valuable factor for predicting the long-term clinical response (P < 0.0005). However, patients with high sphincter pressures and poor treatment results benefited from repeated dilations by having progressively longer remissions. It is concluded that young patients are poor candidates for pneumatic dilation, that treatment should be aimed at near complete inflation of the dilating bag, and that postdilation sphincter pressure may guide further treatment.

PMID 1451966  Gastroenterology. 1992 Dec;103(6):1732-8.
著者: H P Parkman, J C Reynolds, A Ouyang, E F Rosato, J M Eisenberg, S Cohen
雑誌名: Dig Dis Sci. 1993 Jan;38(1):75-85.
Abstract/Text The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7 +/- 2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age > or = 45 years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients < 45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilatation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with pneumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward surgery.

PMID 8420763  Dig Dis Sci. 1993 Jan;38(1):75-85.
著者: Frank Zerbib, Valérie Thétiot, Frédérique Richy, Dafr-Allah Benajah, Laurent Message, Hervé Lamouliatte
雑誌名: Am J Gastroenterol. 2006 Apr;101(4):692-7. doi: 10.1111/j.1572-0241.2006.00385.x.
Abstract/Text INTRODUCTION: In esophageal achalasia, pneumatic dilations (PD) provide short-term and long-term remission rates of 60-90% and 40-50%, respectively. The aim of this study was to evaluate the long-term efficacy of repeated PD as long-term maintenance therapy.
PATIENTS AND METHODS: From 1992 to 2004, 150 patients with esophageal achalasia treated by PD were included in this retrospective study (78 males, mean age 57 +/- 20 yr). PD were performed until remission was achieved (symptom score < or = 3, each item < 2) and subsequently when symptomatic recurrence occurred. A standardized symptoms questionnaire was sent to patients lost to follow-up. Results are expressed as mean +/- SD.
RESULTS: Initial remission was achieved in 137 of 150 (91.3%) patients with 2.67 +/- 1.59 dilations [range 1-12]. Failure and perforation rates were 7.3% (n = 11) and 1.3% (n = 2), respectively. After initial remission, 48 of 137 (35%) patients had recurrent symptoms; the probability to be in remission at 5 and 10 yr was 67% and 50%, respectively. At the end of follow-up (45 +/- 38 months, ext. 2-144) 108 of 137 (78.8%) patients were in remission. Among 112 patients whose symptoms could be treated by repeated PD (per protocol analysis), 108 (96.4%) were in remission (3.5 +/- 2.1 PD, ext. 2-12). In this group, the probability of being in remission after repeated PD at 5 and 10 yr was 96.8% and 93.4%, respectively. No pretherapeutic factor influenced long-term remission rate. The overall prevalence of gastroesophageal reflux was 34.7%.
CONCLUSION: One-third of the patients with esophageal achalasia treated by PD will experience symptomatic recurrence during a 4-yr period. Long-term remission can be achieved in virtually all the patients treated by repeated PD according to an "on-demand" strategy based on symptom recurrence.

PMID 16635216  Am J Gastroenterol. 2006 Apr;101(4):692-7. doi: 10.1111・・・
著者: Michael Hulselmans, Tim Vanuytsel, Toon Degreef, Daniel Sifrim, Willy Coosemans, Toni Lerut, Jan Tack
雑誌名: Clin Gastroenterol Hepatol. 2010 Jan;8(1):30-5. doi: 10.1016/j.cgh.2009.09.020. Epub 2009 Sep 25.
Abstract/Text BACKGROUND & AIMS: Achalasia is treated with pneumatic dilation or Heller myotomy, but studies suggest poor long-term outcomes. We analyzed long-term outcomes after initial pneumatic dilation and studied factors associated with failure.
METHODS: A total of 209 patients (111 men; mean age, 51.2 +/- 1.4 years) with achalasia who were treated with pneumatic dilation between 1992 and 2002 were followed. Outcomes were correlated with demographics, presenting symptoms, manometric features, and treatment variables by using chi(2) and Student t tests.
RESULTS: All patients were initially treated with consecutive esophageal dilations up to balloon diameters of 3.0 (26%), 3.5 (41%), or 4.0 cm (33%). After dilations, mean lower esophageal sphincter (LES) pressure had decreased from 31.3 +/- 1.3 to 14.0 +/- 0.7 mm Hg (P < .0001); dysphagia decreased from 96% to 26%; and 49% had gained an average of 4.6 +/- 0.5 kg (weight loss at presentation was 10.6 +/- 0.7 kg in 39%). During follow-up, 66% required no additional treatment, whereas 23% underwent repeat dilations after 79 +/- 8 months. Patients without recurrence were older (41.2 +/- 2.1 vs 56.6 +/- 1.6 years; P < .0001) and had lower post-treatment LES pressure (17.8 +/- 1.2 vs 12.9 +/- 0.6 mm Hg; P < .005). After 70-month follow-up, balloon dilation yielded good or excellent outcomes in 72% of patients. In nonresponders, rescue surgery yielded higher success rates than botulinum toxin therapy (84% vs 44%). Patient satisfaction ranged from good to excellent in 81% of patients.
CONCLUSIONS: Treating achalasia with initial dilation and then surgery for short-term failures yielded good long-term results in more than 70% and treatment satisfaction in more than 80% of patients. Management of dilation failures is more problematic.

Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 19782766  Clin Gastroenterol Hepatol. 2010 Jan;8(1):30-5. doi: 10・・・
著者: Georgios Karamanolis, Spiros Sgouros, Georgios Karatzias, Efthimia Papadopoulou, Konstantinos Vasiliadis, Gerasimos Stefanidis, Apostolos Mantides
雑誌名: Am J Gastroenterol. 2005 Feb;100(2):270-4. doi: 10.1111/j.1572-0241.2005.40093.x.
Abstract/Text OBJECTIVE: Achalasia is a well-defined esophageal motor disorder for which pneumatic dilation is an established therapeutic method. Even though it has been used for several years, there are limited data on the long-term outcomes of patients treated with this procedure. Hence, we aimed to evaluate the long-term efficacy of pneumatic dilation to control the symptoms of achalasia.
METHODS: The medical records of all patients treated in our unit for achalasia with pneumatic dilation were reviewed. We identified the long-term result of the initial procedure, the date of the first dilation, and the time interval between dilation and retreatment.
RESULTS: Of 260 patients who were treated with pneumatic dilation, 153 (67 men, 86 women) were followed up for more than 5 yr. The mean follow-up period was 11.09 +/- 3.91 yr, and the success rate of the dilation was 75.8%. Among these patients, 35 (19 men, 16 women) had follow-up periods of more than 15 yr. The mean follow-up time of those patients was 16.56 +/- 1.09 yr, and the success rate was 51.4%. Kaplan-Meier survival analysis showed that, overall, 50% of patients develop recurring symptoms after 10.92 yr.
CONCLUSIONS: Although 51.4% of patients continued to be in clinical remission more than 15 yr after the initial pneumatic dilation, the long-term success rate of pneumatic dilation seems to drop progressively with time.

PMID 15667481  Am J Gastroenterol. 2005 Feb;100(2):270-4. doi: 10.1111・・・
著者: Panagiotis Katsinelos, Jannis Kountouras, George Paroutoglou, Athanasios Beltsis, Christos Zavos, Basilios Papaziogas, Kostas Mimidis
雑誌名: World J Gastroenterol. 2005 Sep 28;11(36):5701-5.
Abstract/Text AIM: Although most patients with achalasia respond to pneumatic dilation, one-third experienced recurrence, and prolonged follow-up studies on parameters associated with various outcomes are scanty. In this retrospective study, we reported a 15-years' experience with pneumatic dilation treatment in patients with primary achalasia, and determined whether previously described predictors of outcome remain significant after endoscopic dilation.
METHODS: Between September 1989 and September 2004, 39 consecutive patients with primary symptomatic achalasia (diagnosed by clinical presentation, esophagoscopy, barium esophagogram, and manometry) who received balloon dilation were followed up at regular intervals in person or by phone interview. Remission was assessed by a structured interview and a previous symptoms score. The median dysphagia-free duration was calculated by Kaplan-Meier analysis.
RESULTS: Symptoms were dysphagia (n = 39, 100%), regurgitation (n = 23, 58.7%), chest pain (n = 4, 10.2%), and weight loss (n = 26, 66.6%). A total of 74 dilations were performed in 39 patients; 13 patients (28%) underwent a single dilation, 17 patients (48.7%) required a second procedure within a median of 26.7 mo (range 5-97 mo), and 9 patients (23.3%) underwent a third procedure within a median of 47.8 mo (range 37-120 mo). Post-dilation lower esophageal sphincter (LES) pressure, assessed in 35 patients, has decreased from a baseline of 35.8+/-10.4 - 10.0+/-7.1 mmHg after the procedure. The median follow-up period was 9.3 years (range 0.5-15 years). The dysphagia-free duration by Kaplan-Meier analysis was 78%, 61% and 58.3% after 5, 10 and 15 years respectively.
CONCLUSION: Balloon dilation is a safe and effective treatment for primary achalasia. Post-dilation LES pressure estimation may be useful in assessing response.

PMID 16237769  World J Gastroenterol. 2005 Sep 28;11(36):5701-5.
著者: Guy E Boeckxstaens, Vito Annese, Stanislas Bruley des Varannes, Stanislas Chaussade, Mario Costantini, Antonello Cuttitta, J Ignasi Elizalde, Uberto Fumagalli, Marianne Gaudric, Wout O Rohof, André J Smout, Jan Tack, Aeilko H Zwinderman, Giovanni Zaninotto, Olivier R Busch, European Achalasia Trial Investigators
雑誌名: N Engl J Med. 2011 May 12;364(19):1807-16. doi: 10.1056/NEJMoa1010502.
Abstract/Text BACKGROUND: Many experts consider laparoscopic Heller's myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder.
METHODS: We randomly assigned patients with newly diagnosed achalasia to pneumatic dilation or LHM with Dor's fundoplication. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). The primary outcome was therapeutic success (a drop in the Eckardt score to ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for retreatment, pressure at the lower esophageal sphincter, esophageal emptying on a timed barium esophagogram, quality of life, and the rate of complications.
RESULTS: A total of 201 patients were randomly assigned to pneumatic dilation (95 patients) or LHM (106). The mean follow-up time was 43 months (95% confidence interval [CI], 40 to 47). In an intention-to-treat analysis, there was no significant difference between the two groups in the primary outcome; the rate of therapeutic success with pneumatic dilation was 90% after 1 year of follow-up and 86% after 2 years, as compared with a rate with LHM of 93% after 1 year and 90% after 2 years (P=0.46). After 2 years of follow-up, there was no significant between-group difference in the pressure at the lower esophageal sphincter (LHM, 10 mm Hg [95% CI, 8.7 to 12]; pneumatic dilation, 12 mm Hg [95% CI, 9.7 to 14]; P=0.27); esophageal emptying, as assessed by the height of barium-contrast column (LHM, 1.9 cm [95% CI, 0 to 6.8]; pneumatic dilation, 3.7 cm [95% CI, 0 to 8.8]; P=0.21); or quality of life. Similar results were obtained in the per-protocol analysis. Perforation of the esophagus occurred in 4% of the patients during pneumatic dilation, whereas mucosal tears occurred in 12% during LHM. Abnormal exposure to esophageal acid was observed in 15% and 23% of the patients in the pneumatic-dilation and LHM groups, respectively (P=0.28).
CONCLUSIONS: After 2 years of follow-up, LHM, as compared with pneumatic dilation, was not associated with superior rates of therapeutic success. (European Achalasia Trial Netherlands Trial Register number, NTR37, and Current Controlled Trials number, ISRCTN56304564.).

PMID 21561346  N Engl J Med. 2011 May 12;364(19):1807-16. doi: 10.1056・・・
著者: S Kostic, A Kjellin, M Ruth, H Lönroth, E Johnsson, M Andersson, L Lundell
雑誌名: World J Surg. 2007 Mar;31(3):470-8. doi: 10.1007/s00268-006-0600-9.
Abstract/Text BACKGROUND: The most effective therapeutic strategy in newly diagnosed achalasia is yet to be established. Therefore we designed a study in which pneumatic dilatation was compared to laparoscopic cardiomyotomy to which was added a partial posterior fundoplication.
PATIENTS AND RESULTS: A series of 51 patients (24 males, mean age 44 years) were randomly allocated to the therapeutic modalities (dilatation = 26, surgery = 25). All patients were followed for at least 12 months, and during that period the pneumatic dilatations strategy had significantly more treatment failures (P = 0.04). Only minor differences emerged between the study groups when symptoms, dysphagia scorings, and quality-of-life assessments were evaluated 12 months after initiation of therapy.
CONCLUSIONS: Laparoscopic myotomy was found to be superior to an endoscopic balloon dilatation strategy in the treatment of achalasia when studied during the first 12 months after treatment.

PMID 17308851  World J Surg. 2007 Mar;31(3):470-8. doi: 10.1007/s00268・・・
著者: Haruhiro Inoue, Shin-Ei Kudo
雑誌名: Nihon Rinsho. 2010 Sep;68(9):1749-52.
Abstract/Text INTRODUCTION: To establish less invasive permanent treatment for esophageal achalasia, per-oral endoscopic myotomy (POEM) was addressed.
PATIENTS: POEM was performed in 43 consecutive cases of achalasia. Among them, nine cases of sigmoidal achalasia were involved. POEM got IRB approval from our hospital. Written informed consent was given to all patients.
PROCEDURE: After creating submucosal tunnel, endoscopic myotomy of circular muscle bundles was carried out at approximately 12cm in total length (10 cm in distal esophagus and 2 cm cardia). Smooth passing of endoscope through GE junction was confirmed at the end of the procedure.
RESULTS: In all cases symptoms of achalasia were dramaticaly reduced or disappeared. Resting pressure was 52.1 mmHg before POEM, and reduced to 18.8 mmHg after procedure. No specific complications related to POEM were experienced. During follow-up period, no additional treatment and no medication were necessary.
CONCLUSION: Short-term outcome of POEM was excellent with no serious complications. Long-term follow up is scheduled.

PMID 20845759  Nihon Rinsho. 2010 Sep;68(9):1749-52.
著者: Lee L Swanström, Erwin Rieder, Christy M Dunst
雑誌名: J Am Coll Surg. 2011 Dec;213(6):751-6. doi: 10.1016/j.jamcollsurg.2011.09.001. Epub 2011 Oct 13.
Abstract/Text BACKGROUND: Peroral endoscopic myotomy (POEM) has recently been described in humans as a treatment for achalasia. This concept has evolved from developments in natural orifice translumenal endoscopic surgery (NOTES) and has the potential to become an important therapeutic option. We describe our approach as well as our initial clinical experience as part of an ongoing study treating achalasia patients with POEM.
STUDY DESIGN: Five patients (mean age 64 ± 11 years) with esophageal motility disorders were enrolled in an IRB-approved study and underwent POEM. This completely endoscopic procedure involved a midesophageal mucosal incision, a submucosal tunnel onto the gastric cardia, and selective division of the circular and sling fibers at the lower esophageal sphincter. The mucosal entry was closed by conventional hemostatic clips. All patients had postoperative esophagograms before discharge and initial clinical follow-up 2 weeks postoperatively.
RESULTS: All (5 of 5) patients successfully underwent POEM treatment, and the myotomy had a median length of 7 cm (range 6 to 12 cm). After the procedure, smooth passage of the endoscope through the gastroesophageal junction was observed in all patients. Operative time ranged from 120 to 240 minutes. No leaks were detected in the swallow studies and mean length of stay was 1.2 ± 0.4 days. No clinical complications were observed, and at the initial follow-up, all patients reported dysphagia relief without reflux symptoms.
CONCLUSIONS: Our initial experience with the POEM procedure demonstrates its operative safety, and early clinical results have shown good results. Although further evaluation and long-term data are mandatory, POEM could become the treatment of choice for symptomatic achalasia.

Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 21996484  J Am Coll Surg. 2011 Dec;213(6):751-6. doi: 10.1016/j.j・・・
著者: Daniel von Renteln, Haruhiro Inoue, Hiromi Minami, Yuki Birgit Werner, Andrea Pace, Jan Felix Kersten, Chressen Catharina Much, Guido Schachschal, Oliver Mann, Jutta Keller, Karl-Hermann Fuchs, Thomas Rösch
雑誌名: Am J Gastroenterol. 2012 Mar;107(3):411-7. doi: 10.1038/ajg.2011.388. Epub 2011 Nov 8.
Abstract/Text OBJECTIVES: Endoscopic balloon dilatation and laparoscopic myotomy are established treatments for achalasia. Recently, a new endoscopic technique for complete myotomy was described. Herein, we report the results of the first prospective trial of peroral endoscopic myotomy (POEM) in Europe.
METHODS: POEM was performed under general anesthesia in 16 patients (male:female (12:4), mean age 45 years, range 26-76). The primary outcome was symptom relief at 3 months, defined as an Eckhard score ≤3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.
RESULTS: A 3-month follow-up was completed for all patients. Treatment success (Eckhard score ≤3) was achieved in 94% of cases (mean score pre- vs. post-treatment (8.8 vs. 1.4); P<0.001). Mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post-treatment (P<0.001). No patient developed symptoms of gastro-esophageal reflux after treatment, but one patient was found to have an erosive lesion (LA grade A) on follow-up esophagogastroduodenoscopy. No patient required medication with proton pump inhibitors or antacids after POEM.
CONCLUSIONS: POEM is a promising new treatment for achalasia resulting in short-term symptom relief in >90% of cases. Studies evaluating long-term efficacy and comparing POEM with established treatments have been initiated.

PMID 22068665  Am J Gastroenterol. 2012 Mar;107(3):411-7. doi: 10.1038・・・
著者: Neil H Bhayani, Ashwin A Kurian, Christy M Dunst, Ahmed M Sharata, Erwin Rieder, Lee L Swanstrom
雑誌名: Ann Surg. 2014 Jun;259(6):1098-103. doi: 10.1097/SLA.0000000000000268.
Abstract/Text OBJECTIVE: To compare symptomatic and objective outcomes between HM and POEM.
BACKGROUND: The surgical gold standard for achalasia is laparoscopic Heller myotomy (HM) and partial fundoplication. Per-oral endoscopic myotomy (POEM) is a less invasive flexible endoscopic alternative. We compare their safety and efficacy.
METHODS: Data on consecutive HMs and POEMs for achalasia from 2007 to 2012 were collected.
PRIMARY OUTCOMES: swallowing function-1 and 6 months after surgery.
SECONDARY OUTCOMES: operative time, complications, postoperative gastro-esophageal reflux disease (GERD).
RESULTS: There were 101 patients: 64 HMs (42% Toupet and 58% Dor fundoplications) and 37 POEMs. Presenting symptoms were comparable. Median operative time (149 vs 120 min, P < 0.001) and mean hospitalization (2.2 vs 1.1 days, P < 0.0001) were significantly higher for HMs. Postoperative morbidity was comparable. One-month Eckardt scores were significantly better for POEMs (1.8 vs 0.8, P < 0.0001). At 6 months, both groups had sustained similar improvements in their Eckardt scores (1.7 vs 1.2, P = 0.1).Both groups had significant improvements in postmyotomy lower esophageal sphincter profiles. Postmyotomy resting pressures were higher for POEMs than for HMs (16 vs 7.1 mm Hg, P = 0.006). Postmyotomy relaxation pressures and distal esophageal contraction amplitudes were not significantly different between groups. Routine postoperative 24-hour pH testing was obtained in 48% Hellers and 76% POEMs. Postoperatively, 39% of POEMs and 32% of HM had abnormal acid exposure (P = 0.7).
CONCLUSIONS: POEM is an endoscopic therapy for achalasia with a shorter hospitalization than HM. Patient symptoms and esophageal physiology are improved equally with both procedures. Postoperative esophageal acid exposure is the same for both. The POEM is comparable with laparoscopic HM for safe and effective treatment of achalasia.

PMID 24169175  Ann Surg. 2014 Jun;259(6):1098-103. doi: 10.1097/SLA.00・・・
著者: Francisco Schlottmann, Daniel J Luckett, Jason Fine, Nicholas J Shaheen, Marco G Patti
雑誌名: Ann Surg. 2018 Mar;267(3):451-460. doi: 10.1097/SLA.0000000000002311.
Abstract/Text OBJECTIVE: To compare the outcome of per oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia.
BACKGROUND: Over the last 2 decades, LHM has become the primary form of treatment in many centers. However, since the first description of POEM in 2010, this technique has widely disseminated, despite the absence of long-term results and randomized trials.
METHODS: A systematic Medline literature search of articles on LHM and POEM for the treatment of achalasia was performed. The main outcomes measured were improvement of dysphagia and posttreatment gastroesophageal reflux disease (GERD). Linear regression was used to model the effect of each procedure on the different outcomes.
RESULTS: Fifty-three studies reported data on LHM (5834 patients), and 21 articles examined POEM (1958 patients). Mean follow-up was significantly longer for studies of LHM (41.5 vs. 16.2 mo, P < 0.0001). Predicted probabilities for improvement in dysphagia at 12 months were 93.5% for POEM and 91.0% for LHM (P = 0.01), and at 24 months were 92.7% for POEM and 90.0% for LHM (P = 0.01). Patients undergoing POEM were more likely to develop GERD symptoms (OR 1.69, 95% CI 1.33-2.14, P < 0.0001), GERD evidenced by erosive esophagitis (OR 9.31, 95% CI 4.71-18.85, P < 0.0001), and GERD evidenced by pH monitoring (OR 4.30, 95% CI 2.96-6.27, P < 0.0001). On average, length of hospital stay was 1.03 days longer after POEM (P = 0.04).
CONCLUSIONS: Short-term results show that POEM is more effective than LHM in relieving dysphagia, but it is associated with a very high incidence of pathologic reflux.

PMID 28549006  Ann Surg. 2018 Mar;267(3):451-460. doi: 10.1097/SLA.000・・・

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