Are human herpes viruses or measles virus associated with esophageal achalasia?

In order to test the hypothesis that esophageal achalasia may be due to neurotropic viral damage to the esophageal myenteric plexus, esophageal tissue with or without achalasia was analyzed by polymerase chain reaction for the presence of human herpes virus DNA or measles virus RNA. The DNA and RNA were extracted from the esophageal muscle of 12 patients with achalasia and six patients with upper esophageal carcinoma. Peripheral blood mononuclear cells from eight adult volunteers and two samples of umbilical blood mononuclear cells were also used as controls. PCR amplification with a pair of primers specific for herpes simplex type 1 and 2 viruses identified 92-bp fragments in nearly all specimens, including those without achalasia. Each 92-bp fragment was confirmed to be identical to a single herpes simplex virus sequence by automated DNA sequence analysis. No amplification for five other herpes viruses or measles virus was detected. Therefore, a specific viral etiology for achalasia was not identified in this study.     

Spectrum of histopathologic findings in patients with achalasia reflects different etiologies

BACKGROUND: The etiology of achalasia is still unknown. The aim of the present study was to elucidate its underlying pathologies and their chronology by investigation of esophageal specimens in patients undergoing surgery (esophageal resection or myotomy) for achalasia. METHODS: In 17 patients with achalasia, histopathologic examinations of the esophageal wall focussing on the myenteric plexus were performed. Preoperative diagnosis was based on clinical evaluation, esophagogastroscopy, barium esophagogram in all, and esophageal manometry in eight patients. The median age at the time of surgery was 54 years (range: 14-78 years). In eight cases, the complete esophageal, body and in nine cases a smooth muscle biopsy including parts of the myenteric plexus from the distal part of the esophagus (high pressure zone) was available. The tissue specimens were fixed in formalin and embedded in paraffin. The staining procedures were hematoxylin and eosin (HE), Elastica van Gieson (EvG), and periodic acid-Schiff (PAS) reaction. Immunohistochemical examinations were performed with antibodies against B and T lymphocytes, neurofilament, protein gene-related product (PGP 9.5), S-100 protein, myosin, desmin, smooth muscle actin and substance P. RESULTS: In 13 of 17 patients, a significant reduction of the number of intramural ganglion cells was present. Common findings were a severe fibrosis of the smooth muscle layer (10/17) and obvious myopathic changes of the smooth muscle cells (5/17). Staining for B and T lymphocytes found signs of inflammation in mucosal and muscular areas. Three patients exhibited a marked invasion of eosinophilic granulocytes of the muscularis propria (eosinophilia). Esophageal carcinoma had developed in three patients (squamous cell carcinoma in two and carcinoma in situ in another patient with Barrett's esophagus and high-grade dysplasia). Severe inflammatory reactions (neural, eosinophilic and mucosal) dominated in patients with a longstanding history of achalasia (>10 years) as well as a marked endomysial fibrosis. CONCLUSIONS: The histopathological investigations of the esophageal wall in 17 patients undergoing esophageal resection or myotomy for achalasia suggest that the reduction of intramural ganglion cells might be a secondary change, probably due to inflammation triggered by autoimmune mechanisms or a chronic degenerative process of the central and/or peripheral part of the vagal nerve. The primary lesion could also be a severe myopathy of the smooth muscle cells.     

Family case of achalasia cardia: Case report and review of literature

Achalasia cardia is an idiopathic disease that occurs as a result of inflammation and degeneration of myenteric plexi leading to the loss of postganglionic inhibitory neurons required for relaxation of the lower esophageal sphincter and peristalsis of the esophagus.The main symptoms of achalasia are dysphagia,regurgitation,chest pain and weight loss.At present,there are three main hypotheses regarding etiology of achalasia cardia which are under consideration,these are genetic,infectious and autoimmune.Genetic theory is one of the most widely discussed.Case report given below represents an inheritable case of achalasia cardia which was not diagnosed for a long time in an 81-year-old woman and her 58-year-old daughter.     

Comparison between idiopathic achalasia and achalasia caused by Chagas' disease: a review on the publications about the subject

BACKGROUND: Although idiopathic achalasia and achalasia caused by Chagas' disease have the same clinical manifestations and treatment, both with destruction of the esophageal myenteric plexus, it is possible that there are differences in the alterations of esophageal motility between the two diseases, caused by different grades of impairment of the excitatory and inhibitory esophageal neurons. AIMS: We performed a review of papers with results about the pathophysiology and esophageal motility alterations in idiopathic achalasia and Chagas' disease. DATE SOURCES: We reviewed papers which included data about the characteristics of idiopathic achalasia and Chagas' disease. DATA SYNTHESIS: Impairment of inhibitory esophageal neurons was shown in the two diseases. The results of the studies of the effects of atropine, edrophonium and botulin toxin suggested that the excitatory innervation is more intensely impaired in Chagas' disease than in idiopathic achalasia, explaining the increase in the lower esophageal sphincter pressure found in achalasia. The patients with Chagas' disease have more circulating muscarinic cholinergic receptor M2 autoantibodies than patient with idiopathic achalasia. The duration of the contractions in the esophageal body is longer in idiophatic achalasia than in Chagas' disease. CONCLUSIONS: The papers that studied Chagas' disease and idiopathic achalasia, mainly those which studied both diseases with the same methods, suggested that there are different grades of esophageal involvement by the two diseases, mainly the most important involvement of excitatory innervation in Chagas' disease than in idiopathic achalasia.     

Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract

It has been demonstrated that nitric oxide (NO) is a major inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter in the gastrointestinal (GI) tract. NO released in response to nerve stimulation of the myenteric plexus causes relaxation of the smooth muscle. NO is synthesized by the activation of neuronal NO synthase (nNOS) in the myenteric plexus. Released NO plays an important physiological role in various parts of the GI tract. NO regulates the muscle tone of the sphincter in the lower esophagus, pylorus, sphincter of Oddi, and anus. NO also regulates the accommodation reflex of the fundus and the peristaltic reflex of the intestine. Previous studies have shown that NOS inhibitors delay gastric emptying and colonic transit. The reduction of nNOS expression, associated with impaired local production of NO, may be responsible for motility disorders in the GI tract. There is accumulated evidence that dysfunction of NO neurons in the myenteric plexus may cause various GI diseases. These reports are reviewed and possible mechanisms of altered nNOS expression are discussed in this article. In particular, impaired nNOS synthesis of the myenteric plexus seems to be an important contributing factor to the pathogenesis of achalasia, diabetic gastroparesis, infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and Chagas' disease. Reduced NO release and/or nNOS expression are suspicious in a subset of patients with functional dyspepsia. Although the etiology of intestinal pseudo-obstruction remains unknown, it is conceivable that extrinsic denervation may upregulate nNOS expression, resulting in enhanced muscular relaxation and disturbed peristalsis. An animal model of colitis showed impaired nNOS expression in the colonic myenteric plexus. Antecedent infection may be associated with the impaired NO pathways observed in functional dyspepsia, colitis, and Chagas' disease.     

Childhood achalasia: a separate entity?

BACKGROUND: Achalasia in childhood is rare, also the etiology and the pathogenesis of the early onset ort he disease is practically unknown. Little is known about the neuropathological changes in structure of the esophageal wall in non-hereditary, sporadic achalasia in children and ist differentiation to that in adults. The aim of our study was to examine the morphological properties or high-pressure zone of the lower esophageal sphincter in children who had undergone a Heller myotomy because of achalasia as well as to compare them with the pathological findings in adults. METHODS: Muscle biopsies of the smooth musculature, a 20 x 10 mm long segment of the myenteric of the distal esophagus (lower boundary of the esophageal incision of the myotomy), were taken for histopathological and immunohistochemical studies. RESULTS: A conspicuous histomorphological finding was a marked reduction of the myenteric ganglion through to complete aganglionosis of the high-pressure zone of the lower esophageal sphincter. In contrast to achalasia in adults, neural inflammation was found only rarely. A pronounced fibrosis of the smooth muscle layers was found in all patients whereas muscular hypertrophy or visceral myopathy was not present. The interstitial Cajal cells were reduced, similar to those in adults. CONCLUSIONS: The variability of the clinical and pathological properties in cases of childhood achalasia are indicative of a complex pattern of varying etiologies and a comparison with the disease in adults does not, in principle, allow the assumption of a separate clinical entity. The present findings are compatible with the histopathological results of hereditary achalasia in children as described for Allgrove's syndrome.     

Pseudoachalasia: a case series and analysis of the literature

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.     

Achalasia: A review of clinical diagnosis,epidemiology, treatment and outcomes

Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function.Historically,annual achalasia incidence rates were believed to be low,approximately 0.5-1.2 per 100000.More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations.The aetiology of achalasia is still unclear but is likely to be multi-factorial.Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus,which elicits an autoimmune response.Risk of achalasia may be elevated in a sub-group of genetically susceptible people.Improvement in the diagnosis of achalasia,through the introduction of high resolution manometry with pressure topography plotting,has resulted in the development of a novel classification system for achalasia.This classification system can evaluate patient prognosis and predict responsiveness to treatment.There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller’s myotomy procedure in the treatment of achalasia.A recent com-parative study found equal efficacy,suggesting that patient preference and local expertise should guide the choice.Although achalasia is a relatively rare condition,it carries a risk of complications,including aspiration pneumonia and oesophageal cancer.The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia,however the absolute excess risk is small.Therefore,it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective.     

贲门失弛缓症动物模型的建立及其机制探讨

背景:贲门失弛缓症是一种常见的食管动力障碍性疾病,其病因不清,目前尚缺乏有效根治措施。目的:建立猫贲门失弛缓症动物模型并探讨其发生机制,为贲门失弛缓症的根治提供依据。方法:胃镜下将苄基-二甲基-十四烷基氯化铵(BAC)注射至猫食管下括约肌(LES)周围,对照组注射生理盐水,观察动物进食和体重的变化。第8周时行食管钡餐检查,计算食管钡剂潴留率;测定LES静息压力(LESBP)、松弛率和松弛度;观察不同药物对体内LESBP和体外LES肌环张力的影响以及肌环对电场刺激的反应。采用免疫组化染色分析一氧化氮合酶(NOS)阳性神经元在LES肌环中的分布。结果:第8周时,BAC处理组进食减少,体重显著减轻(-P<0.05),食管钡剂潴留率显著高于对照组(P<0.01),LESBP显著增高(P<0.05),LES松弛率和松弛度显著减低(P<0.05),L-精氨酸对LESBP无影响,但硝普钠可使LESBP显著降低(P<0.05);对照组LESBP无明显变化,L-精氨酸和硝普钠均可使LESBP显著降低(P<0.05)。两组体外LES肌环由乙酰胆碱和硝普钠引起的收缩和舒张反应无明显差别,L-精氨酸可使对照组肌环松弛,但不能使BAC处理组肌环松弛,电场刺激不能引起BAC处理组肌环松弛,但能引起收缩。免疫组化染色提示BAC处理组LES肌环肌间神经丛NOS阳性神经元缺失。结论:通过LES注射BAC成功建立了     

Achalasia: virus-induced euthanasia of neurons?

Achalasia, a motor disorder of the esophagus, is characterized by myenteric plexitis leading to neuronal loss. Cytotoxic T cells, isolated from the lower esophageal sphincter of achalasia patients, respond to human herpes virus-1 (HSV-1) with γ-IFN (and to a lesser extent IL-2) production and clonal proliferation. In addition, HSV-1 DNA was demonstrated in the vast majority of patients, but also in controls. These exciting data suggest that achalasia is an immune-mediated inflammatory disease in which a (latent) infection with HSV-1 leads to persistent immune activation and self-destruction of esophageal neurons, most likely in genetic susceptible subjects only.     

Esophageal motility disorders: current concepts of pathogenesis and treatment.

Current concepts of esophageal motility disorders are summarized. Primary data sources were located via MEDLINE or cross-citation. No attempt was made to be comprehensive or inclusive of the literature because fewer than 10% of citations are discussed. Instead, emphasis was placed on new developments in diagnosis, therapeutics and practice patterns. Controlled therapeutic trials and pathophysiological observations are emphasized. Achalasia is a rare disease of failed lower sphincter relaxation and aperistalsis. Diffuse esophageal spasm (DES), an equally rare disease, is defined by nonpropagated esophageal contractions. Nonspecific motility disorders, including nutcracker esophagus and hypertensive lower esophageal sphincter, are identified only by manometry and are 10 times as prevalent. Neuromuscular pathology is evident only with achalasia (myenteric plexus neuron destruction). Pharmacological therapies have limited efficacy with achalasia, more limited efficacy with DES and no efficacy with the nonspecific motility disorders. More efficacious therapies for the nonspecific disorders are directed at associated reflux disease or psychiatric disorders. Pneumatic dilation is effective therapy for achalasia in 72% of instances but frequently requires repeat dilation and is complicated by a 3% perforation rate. Surgical myotomy is effective in 88% of patients with achalasia; morbidity from thoracotomy has been the major limitation but has been sharply reduced with a laparoscopic approach. In conclusion, although it has been suggested that esophageal motility disorders are distinct clinical entities, critical review of the literature supports this only in the case of achalasia, a disease of well defined pathophysiology, functional disturbance and therapies. This clarity diminishes progressively for DES and nonspecific esophageal motility disorders.     

Neuromuscular control of esophageal peristalsis

The esophagus is a muscular conduit connecting the pharynx and the stomach. Its function is controlled by an intrinsic nervous system and by input from the central nervous system through the vagus nerve. Peristalsis in its striated muscle is directed by sequential vagal excitation arising in the brain stem, whereas peristalsis in its smooth muscle involves complex interactions among the central and peripheral neural systems and the smooth muscle elements of the esophagus. The peripheral neuronal elements responsible for producing esophageal off-response, relaxation of the lower esophageal sphincter, and hyperpolarization of the circular esophageal muscle cells reside in the myenteric plexus of the esophagus. For many years these nerves were considered nonadrenergic and noncholinergic because the inhibitory neurotransmitter released on their activation was unknown. We now know that nitric oxide or a related compound is that inhibitory neurotransmitter. The primary excitatory neurotransmitter controlling esophageal motor function is acetylcholine. Some disorders of esophageal motor function, including diffuse esophageal spasm and achalasia, may result from defects in or an imbalance between these excitatory and inhibitory neuromuscular systems.     

An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagus

Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines – namely, tumor necrosis factor alpha and interleukin‐2 – in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin‐2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin‐2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t‐test, Fisher's exact test, or Mann–Whitney U test, with a two‐tailed P‐value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin‐2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease.     

Achalasia

Achalasia is a rare motor disorder of the esophagus, characterized by the absence of peristalsis and impaired swallow-induced relaxation. These motor abnormalities result in stasis of ingested food in the esophagus, leading to clinical symptoms, such as dysphagia, regurgitation of food, retrosternal pain and weight loss. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. In terms of diagnosis, esophageal manometry is the gold standard to diagnose achalasia. Still, its role in post-treatment surveillance remains controversial. Radiological studies support the initial diagnosis of achalasia and have been proposed for detecting preclinical symptomatic recurrence. Although endoscopy is considered to have a poor sensitivity and specificity in the diagnosis of achalasia, it has an important role in ruling out secondary causes of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the lower esophageal sphincter (LES) pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids.     

The prevalence of autoimmune disease in patients with esophageal achalasia

Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10–15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5–19), 8.5 times as likely to have hypothyroidism (95% CI 5.0–14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9–205), 43 times as likely to have systemic lupus erythematosus (95% CI 12–154), and 259 times as likely to have uveitis (95% CI 13–1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5–5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.     

Role of deglutitive inhibition in the pathophysiology of esophageal primary motor disorders]

The esophageal primary motor disorders like achalasia, diffuse esophageal spasm or the nutcracker can involve the upper esophageal sphincter, the esophageal body, the lower esophageal sphincter or a combination of them. This article will focus on the esophageal body and abnormal peristalsis. A normal esophageal peristaltic contraction occurs after a latency period following a swallow and requires a minimum amplitude to be propulsive. Abnormal latencies may generate simultaneous contractions whereas low amplitude contractions may be inefficient i.e. GERD and high amplitude contractions my provoke chest pain or dysfagia i.e. diffuse spasm. The latency period between deglutition and contraction is due to a muscle inhibition immediately after the swallow. This inhibition is due to release of NO by an inhibitory neurone located in the myenteric plexus. At the end of the inhibition, the contraction occurs due to release of acetyl choline by an excitatory cholinergic neurone. The exact interplay between these two neurones will determine the or propagation velocity and the amplitude of esophageal contractions. Patients with achalasia have a predominant loss of inhibitory neurones (VIP and NOS) with a relative preservation of excitatory cholinergic neurones. The histophatologic and immunohistochemical status in patients with esophageal primary motor disorders other than achalasia is poorly characterised Examples of deglutitive inhibition in the esophagus can be observed during the relaxation of the lower esophageal sphincter or when a subject swallows very frequently. In order to quantify deglutitive inhibition we developed a method that induces an artificial high pressure zone in the mid esophageal body. During the latency period after a swallow, the high pressure zone relaxes (is inhibited). With this method, we could measure the magnitude and duration of the inhibitory phenomenon. There is a very good correlation between the degree of deglutitive inhibition and propagation velocity of esophageal contractions. The less inhibition, the faster the propagation velocity of contractions. Simultaneous contractions are the consequence of absent inhibition. Patients with esophageal primary motor disorders may have very fast propagating contractions and a small percentage of simultaneous contractions or up to 100% of simultaneous contractions. The correlation between the degree of inhibition and propagation velocity of contractions suggests that the different primary motor disorders are the expression of a progressive failure in esophageal inhibition.     

Hydrogen sulfide synthesis enzymes reduced in lower esophageal sphincter of patients with achalasia

The etiology of achalasia remains largely unknown. Considerable evidence reveals that the lower esophageal sphincter dysfunction is due to the lack of inhibitory neurotransmitter, secondary to esophageal neuronal inflammation or loss. Recent studies suggest hydrogen sulfide may act as an inhibitory transmitter in gastrointestinal tract, but study about hydrogen sulfide in human esophagus still lack. The aim of the study was to investigate if hydrogen sulfide synthesis enzymes could be detected in human esophagus and if the synthesis of the endogenous hydrogen sulfide could be affected in achalasia patients. Tissue samples in cardia, lower esophageal sphincter, 2 cm and 4 cm above lower esophageal sphincter were obtained from achalasia patients undergoing peroral endoscopic myotomy. Control tissues in lower esophageal sphincter were obtained from esophageal carcinoma patients. Expression of cystathionine‐β‐synthase and cystathionine‐γ‐lyase in lower esophageal sphincter of achalasia patients and control were detected by immunohistochemical staining. In addition, expression of cystathionine‐β‐synthase and cystathionine‐γ‐lyase were compared among different parts of esophagus in achalasia patients. Compared with control, the expression of cystathionine‐β‐synthase and cystathionine‐γ‐lyase in lower esophageal sphincter of achalasia patients was significantly reduced (χ² = 11.429, P = 0.010). The expression of cystathionine‐β‐synthase and cystathionine‐γ‐lyase were lower in lower esophageal sphincter than that in 2 cm and 4 cm above lower esophageal sphincter, respectively (all P < 0.05). In conclusion, the expression of hydrogen sulfide synthesis enzymes, cystathionine‐β‐synthase and cystathionine‐γ‐lyase, can be detected in human esophagus and is reduced in patients with achalasia, which implicates the involvement of the two hydrogen sulfide synthesis enzymes in the pathophysiology of achalasia.     

Achalasia or carcinoma? The significance of the mecholyl test

Two cases of fundal gastric carcinoma producing a typical picture of achalasia, including a positive Mecholyl test, are described. The differential diagnosis of both conditions is discussed. Hypersensitivity to cholinergic agents should be interpreted only as representing anatomic and/or physiologic derangement of the myenteric plexus of the esophagus and should not be considered as pathognomonic of achalasia. Fundal carcinoma producing infiltrating lesions at the level of the myenteric plexus of the esophagus may closely simulate primary achalasia. The evaluation of achalasia in a given patient is not complete without careful radiologic and endoscopic studies with biopsy and cytologic sampling of any suspicious area.