Differences in response of the proximal esophagus to wet swallows in patients of Chagas'' disease and idiopathic achalasia

Chagas' disease and idiopathic achalasia have similar esophageal manifestations such as absent or incomplete lower esophageal sphincter relaxation and aperistalsis in the esophageal body (alterations seen mainly in the distal esophageal body). Our aim in this paper was to study the response of the proximal esophageal body to wet swallows in patients with Chagas' disease and patients with idiopathic achalasia. We retrospectively analyzed the time interval between the onset of the pharyngeal contractions 1 cm proximal to the upper esophageal sphincter, as well as 5 cm distal to the pharyngeal measurement. Amplitude, duration and area under the curve of contractions in the proximal esophagus were also determined in 42 patients with Chagas' disease (15 with associated esophageal dilatation), 21 patients with idiopathic achalasia (14 with concomitant esophageal dilatation) and 31 control subjects. The time between the onset of pharyngeal and proximal esophageal contractions was longer in patients with Chagas' disease and in those with esophageal dilatation (1.39 +/- 0.16 s) than in control subjects (0.86 +/- 0.04 s, P < 0.01). The amplitude of proximal esophageal contractions was lower in patients with idiopathic achalasia and esophageal dilatation (60.9 +/- 16.3 mmHg) than in control subjects (89.7 +/- 6.9 mmHg, P = 0.06). The authors conclude that in patients with advanced esophageal disease, the proximal esophageal contractions in Chagas' disease have a delayed response to wet swallows when compared with controls, and that the amplitude of proximal esophageal contractions was lower than expected in patients with idiopathic achalasia.     

Efficacy of botulinum toxin injection before pneumatic dilatation in patients with idiopathic achalasia

Graded pneumatic dilatation (PD) is an appropriate long-term therapy and botulinum toxin injection (BT) is a relatively short-term therapy in idiopathic achalasia. Their combination has not been previously scrutinized. This study aimed to evaluate the role of BT in enhancing the efficacy of PD with 30 mm balloons. Patients who underwent PD with 30 mm balloons after botulinum toxin injections and a group of age- and sex-matched controls who were treated only with PD were enrolled in the study. Symptom scores were taken before, 1 month after and then every 3 months after PD. There were no significant differences between the two groups in gender, duration or severity of symptoms. One of the 12 patients in the case group relapsed 30 months after PD but the others were in remission for an average of 25.6 months. In the control group, all the patients relapsed after a mean of 12.6 months and needed a 35-mm PD. The cumulative remission rate was significantly higher in the case group compared with the control group (P < 0.01). The mean symptom score decreased by 76% in the case group (P < 0.001) and 53% in the controls (P < 0.01) at the end of the first month. Neither age, sex, nor duration or severity of symptoms were predictive of patients' responses to treatment. It seems that BT may be a meaningful enhancing factor in long-term efficacy of PD. PD with a 30 mm balloon after a BT session may resolve the need for the future higher grade PD.     

Effect of bolus volume on proximal esophageal contractions of patients with Chagas' disease and patients with idiopathic achalasia

Chagas' disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas' disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas' disease and with idiopathic achalasia. We studied 49 patients with Chagas' disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3‐mL and 6‐mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal‐esophageal time [PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas' disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P≤ 0.02). In Chagas' disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P≤ 0.03).There was no difference between swallows of 3‐ or 6‐mL boluses. There was no difference between patients with Chagas' disease and with idiopathic achalasia. We conclude that patients with Chagas' disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.     

流式微球技术检测血小板膜糖蛋白自身抗体的方法建立及临床价值

目的:建立流式微球技术检测血小板膜表面糖蛋白(GPⅡb/Ⅲa和GPⅠb/IX)特异性自身抗体的方法,并评价其对特发性血小板减少性紫癜(ITP)的诊断价值及临床意义。方法:应用抗人血小板GPⅡb/Ⅲa(CD41a)、GPⅠb/IX(CD42b)单抗包被微球,将血小板从待测血液样本中分离并裂解,血小板裂解后与包被好的微球共同孵育,加入PE标记的羊抗人IgG多克隆抗体,上机检测,流式细胞仪分析ITP组和非免疫性血小板减少组患者自身抗体表达情况。将所测样本的平均荧光强度值(MFI)与正常对照(3个不同正常人血样)MFI的均值进行比较,计算其比率。结果:ITP组该比率均值及范围:GPⅡb/Ⅲa:6.52(0.22～30.20),GPⅠb/IX:6.13(0.56～22.00);非免疫性血小板减少组为:GPⅡb/Ⅲa:1.20(0.32～3.04),GPⅠb/IX:1.302(0.33～3.56);正常对照组比率均值及范围为:GPⅡb/Ⅲa:0.96(0.23～2.28),GPⅠb/IX:0.97(0.22～2.13)。ITP组2种自身抗体荧光强度比率明显高于非免疫性血小板减少组和正常对照组(均P<0.01)。以正常对照...     

Long-term follow-up of achalasia patients treated with botulinum toxin

AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.     

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

Although both primary biliary cirrhosis （PBC） and idiopathic thrombocytopenic purpura （ITP） are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis （PBC） with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.     

Ethanolamine oleate as a novel therapy is effective in resistant idiopathic achalasia

Idiopathic achalasia (IA) is a primary motor disorder of the esophagus. Recently, ethanolamine oleate (EO) has been introduced as a novel therapy in IA. We investigate the long‐term efficacy of EO injection in the selected IA patients. Two hundred twenty patients with IA were evaluated prospectively. Thirty‐one patients who were resistant to or poor candidate of pneumatic balloon dilation and/or cardiomyotomy were enrolled in this study. EO was injected into the lower esophageal sphincter three times at 2‐week intervals. Patients were evaluated with the achalasia symptom score (ASS), timed barium esophagogram, and manometry before and after the injections. A good response was defined as a greater than 50% reduction from baseline in the ASS, height and/or volume of barium in TBE, and absence of severe dysphagia or regurgitation at 1.5 months after the last injection. Relapse was defined as two or more points increase in dysphagia score after an initial good response. The mean age of patients was 49.32 ± 19.3 years. Twenty‐nine patients had a good response and two had a poor response. The mean ASS decreased from 12.48 (±2.06) to 4.50 (±2.96) (P = 0.0001), and the mean volume of barium decreased from 115.35 (±93.40) to 45.50 (±60.86) mL at 1.5 months after the last injection (P = 0.0001).The mean lower esophageal sphincter pressure was 30.47 ± 13.95 before the treatment and decreased to 14.30 ± 11.89 at 1.5 months after the treatment. (P = 0.0001). The mean duration of follow up was 30.16 ± 11.3 (18–68) months. Twelve patients in whom symptoms relapsed were treated effectively with reinjection. In some patients, minor complications (chest pain and erosion in the distal esophagus) occurred. This study indicates that EO has a long‐term effect and can be considered for use in the selected IA patients.     

Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin's lymphoma

The presence of antinuclear autoantibodies (ANA) was investigated in a large cohort of patients with non-Hodgkin's lymphoma (NHL) in order to assess their frequency, specificity and prognostic relevance. ANA were analysed in 347 patients with different histological subgroups of NHL and in 213 controls using an indirect immunofluorescence technique on HEp2 cells. As the appearance of autoantibodies may be found after treatment of NHL, samples were collected at the time of diagnosis of NHL before any therapy. Sixty-six (19%) NHL patients and 12 (5.6%) patients from the control group displayed ANA. The prevalence between the two groups was found to be significantly higher in NHL patients (P < 0.0001) with a marked increased prevalence in follicular and mantle cell lymphoma subgroups. Autoantibodies directed against mitotic proteins or mitotic-associated proteins were found in 6.9% of NHL patients versus 0.5% in the control group (P < 0.001), with a significantly increased incidence in follicular and mantle cell lymphoma subgroups (P < 0.0001). Some 28% of the patients with positive ANA displayed clinical symptoms that could correspond to classical autoimmune manifestations, this frequency appearing to be higher in the marginal zone/mucosa-associated lymphoid tissue lymphoma subgroup. These data demonstrate a significant incidence of ANA before any treatment in NHL occurrence, which seems to be higher in some histological subgroups with particular ANA, such as ANA directed against mitotic proteins or mitotic-associated proteins.     

Histology of esophageal mucosa from patients with achalasia

When achalasia becomes far advanced and leads to esophageal resection, inflammation of the esophageal mucosa is almost universal. The histology of the esophageal mucosa in less advanced cases of achalasia has not been firmly established. We have studied endoscopic biopsies obtained during evaluation of patients with achalasia. Two to four endoscopic biopsies from the lower esophagus of 26 patients with manometrically verified achalasia were mounted on mesh, serially sectioned, stained, coded and interpreted by two independent observers using recognized criteria. The histological findings were correlated with clinical data. Ten of 26 patients had at least one abnormal biopsy. Five of these 10 patients had a previous Heller myotomy; another patient had several pneumatic dilatations, and two other patients had endoscopically proven candida infections. Of the 16 patients with normal histology, four had prolonged stasis, five had heartburn and one patient had both heartburn and stasis. Unless the patient with achalasia has had a Heller myotomy, balloon dilatation, or a candida infection, the esophageal mucosa on biopsy appears to be within normal limits, even in patients with years of esophageal stasis or complaints of heartburn.     

Abnormal bile flow in patients with achalasia

Background: It has been reported that esophageal achalasia is frequently associated with the dysmotility of other digestive organs. However, the prevalence of extraesophageal complications in patients with achalasia still remains poorly understood. We performed cholescintigraphy, using ^99mTc-pyridoxyl-5-methyl-tryptophan, in patients with esophageal achalasia to assess any possible dysfunction of the sphincter of Oddi associated with achalasia. Methods: Eight patients (two men and six women) were examined to determine the time required for bile to flow from the bile duct to the duodenum. Results: Excretion time of bile was markedly prolonged in five of the eight patients with achalasia. Scintigraphic findings were not correlated with the radiographic classification of achalasia or with the grading of achalasia. Conclusions: The present results suggest that a considerable number of patients with achalasia have dysfunction of the sphincter of Oddi, irrespective of the morphological type of achalasia and the grade of esophageal dilatation. Received: February 7, 2002 / Accepted: September 6, 2002 Reprint requests to: N. Uchida     

Autoimmune comorbidity in achalasia patients

Background and Aim

Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD).

Methods

It was a cross‐sectional and included 114 patients with idiopathic achalasia and 114 age‐matched and sex‐matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records.

Results

Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47–9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00–9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65–6.20).

Conclusions

The non‐negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.     

Remission of arthritis after esophagectomy in three patients with severe achalasia

In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients with extreme obesity. However, this is now done with great restriction due to the risk of complications, for instance, polyarthritis. An association between severe achalasia and arthritis has also been described, but very few articles on this topic are cited in PubMed, and most of the published case reports are old. In this article, we present a retrospective case series of three patients with severe achalasia and arthritis from the departments of rheumatology and surgery at a university hospital. The complaints from the esophagus as well as arthritis were resolved after esophagectomy and esophageal reconstruction. We conclude that severe achalasia can be associated with arthritis, and both can be cured by esophageal reconstruction. Thus, we want to remind of this rare, but probably largely unrecognized, association between achalasia and joint disease.     

Expression of HLA-G in patients with hepatocellular carcinoma

BACKGROUND:Human leukocyte antigen G(HLA-G)is a non-classical major histocompatibility complex class I molecule that has multiple immune regulatory functions including the induction of immune tolerance.The detection of HLA-G expression might serve as a clinical marker in the prediction of clinical outcomes for certain types of carcinoma.Currently, we investigated whether or not HLA-G is also expressed in patients with hepatocellular carcinoma(HCC),and whether the expression has clinical value. METHODS:Serum...     

Prevalence of respiratory symptoms in patients with achalasia

Achalasia is a primary esophageal motor disorder that results in poor clearance of the esophagus. Although an esophagus filled with debris and undigested food should put these patients at risk for aspiration, the frequency with which the latter occurs has never been documented. In this study, we sought to determine the incidence of respiratory symptoms and complaints in patients with achalasia. A comprehensive symptom questionnaire was administered to 110 patients with achalasia presenting to the Swallowing Center at the University of Washington between 1994 and 2008 as part of their preoperative work‐up. Questionnaires were analyzed for the frequency of respiratory complaints in addition to the more typical symptoms of dysphagia, regurgitation, and chest pain. Twenty‐two achalasia patients with respiratory symptoms who had also undergone Heller myotomy and completed a post‐op follow‐up questionnaire were analyzed as a subset. Ninety‐five patients (86%) complained of at least daily dysphagia. Fifty‐one patients (40%) reported the occurrence of at least one respiratory symptom daily, including cough in 41 patients (37%), aspiration (the sensation of inhaling regurgitated esophagogastric material) in 34 patients (31%), hoarseness in 23 patients (21%), wheezing in 17 patients (15%), shortness of breath in 11 patients (10%), and sore throat in 13 patients (12%). Neither age nor gender differed between those with and those without respiratory symptoms. In the subset of patients with respiratory symptoms who had undergone Heller myotomy, respiratory symptoms improved in the majority after the procedure. Patients with achalasia experience respiratory symptoms with much greater frequency than the approximately 10% that was previously believed. Awareness of this association may be important in the workup and ultimate treatment of patients with this uncommon esophageal disorder.     

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.     

Treatment choices and outcomes of patients with manometrically diagnosed achalasia

This prospective population‐based study was designed to evaluate treatment choices in patients with new manometrically diagnosed achalasia and their outcomes. Patients referred to the esophageal function laboratory were enrolled after a new manometric diagnosis of achalasia. Patients completed an initial achalasia symptom score validated questionnaire on their symptom severity, duration, treatment pre‐diagnosis and Medical Outcomes Study 36‐item Short‐Form (SF‐36) survey. Treatment decisions were made by the referring physician and the patient. Follow‐up questionnaires were completed every 3 months for 1 year. Patients who chose not to undergo treatment at 1‐year follow‐up completed another questionnaire after 5 years. Between January 2004 and January 2005, 83 of 124 eligible patients were enrolled. Heller myotomy was performed on 31 patients, three patients received botulinum toxin injections, and 25 patients received 29 pneumatic balloon dilatations. Twenty‐four patients chose to receive no treatment. Following treatment, patients treated with surgery, dilatation and botulinum toxin had an average improvement in achalasia symptom score of 23 +/? 12.2, 17 +/? 10.9, and 9 +/? 14, respectively. Patients receiving no treatment had worsening symptoms with a symptom score change of ?3.5 +/? 11.4. Surgery and dilatation resulted in significant improvement (P < 0.01) relative to no treatment. In univariate logistic regression, symptom severity score (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.00 to 1.08), sphincter tone (OR 1.04, 95% CI 1.00 to 1.09), difficulty swallowing liquids (OR 3.21, 95% 1.15 to 8.99), waking from sleep (OR 2.75, 95% 1.00 to 7.61), and weight loss (OR 5.99, 95% CI 1.93 to 18.58) were all significant in predicting that patients would select treatment. In the multivariate analysis, older age (OR 1.05, 95% CI 1.01 to 1.09) and weight loss (OR 3.91, 95% CI 1.02 to 15.2) were statistically significant for undergoing treatment. At 5 years, five (21%) of those who had initially declined treatment at 1 year ultimately chose a treatment. Patients who finally chose Heller myotomy had lower mental component dimension scores on the SF‐36 at 1 year than those who did not. This study shows that almost one third of patients with manometrically diagnosed achalasia choose not to undergo treatment within 1 year of their diagnosis. Patients who are more symptomatic appear to be more likely to undergo treatment by univariate analysis. In multivariate analysis, increasing age and weight loss are predictive of those who will undergo treatment, with weight loss having the greatest influence. Patients who choose not to undergo treatment make lifestyle changes to maintain their quality of life, and only a minority of them ultimately undergo treatment.