The not-so-rare absent RAIR: Internal anal sphincter achalasia in a review of 1072 children with constipation undergoing high-resolution anorectal manometry.

BACKGROUND: Our objective is to describe the prevalence of patients with internal anal sphincter achalasia (IASA) without Hirschsprung disease (HD) among children undergoing anorectal manometry (ARM) and their clinical characteristics. METHODS: We performed a retrospective review of high-resolution ARM studies performed at our institution and identified patients with an absent rectoanal inhibitory reflex (RAIR). Clinical presentation, medical history, treatment outcomes, and results of ARM and other diagnostic tests were collected. We compared data between IASA patients, HD patients, and a matched control group of patients with functional constipation (FC). KEY RESULTS: We reviewed 1,072 ARMs and identified 109 patients with an absent RAIR, of whom 28 were diagnosed with IASA. Compared to patients with FC, patients with IASA had an earlier onset of symptoms and were more likely to have abnormal contrast enema studies. Compared to patients with HD, patients with IASA were more likely to have had a normal timing of meconium passage, a later onset of symptoms, and were diagnosed at an older age. At the latest follow-up, the majority of patients diagnosed with IASA (54%) were only using oral laxatives. Over half of patients with IASA had been treated with anal sphincter botulinum toxin injection, and 55% reported a positive response. CONCLUSIONS AND INFERENCES: Patients diagnosed with IASA may represent a more severe patient population compared to patients with FC, but have a later onset of symptoms compared to patients with HD. They may require different treatments for their constipation and deserve further study.

Achalasia: what to do in the face of failures of Heller myotomy.

Achalasia is a primary motility disorder of the esophagus, and while there are several treatment options, there is no consensus regarding them. When therapeutic intervention for achalasia fails, a careful evaluation of the cause of the persistent or recurrent symptoms using upper endoscopy, esophageal manometry, and contrast radiologic studies is required to understand the cause of therapy failure and guide plans for subsequent treatment. Options for reintervention are the same as for primary intervention and include pneumatic dilation, botulinum toxin injection, peroral endoscopic myotomy, or redo esophageal myotomy. When reintervention fails or if the esophagus is not amenable to intervention and the disease is considered end-stage, esophagectomy is the last option to manage recurrent achalasia.

Achalasia diagnosed despite normal integrated relaxation pressure responds favorably to therapy.

BACKGROUND: Achalasia diagnosis requires elevated integrated relaxation pressure (IRP; manometric marker of lower esophageal sphincter [LES] relaxation). Yet, some patients exhibit clinical features of achalasia despite normal IRP and have LES dysfunction demonstrable by other means. We hypothesized these patients to exhibit equivalent therapeutic response compared to standard achalasia patients. METHODS: Symptomatic achalasia-like cases, despite normal IRP, displayed evidence of impaired LES relaxation using rapid drink challenge (RDC), solid swallows during high-resolution manometry, and/or barium esophagogram; were treated with achalasia therapies and compared to standard achalasia patients with raised IRP. Outcomes included equivalence for short- and long-term symptom response and stasis on barium esophagogram. KEY RESULTS: Twenty-nine normal IRP achalasia cases (14 males, median age 50 year, median Eckardt 6, barium stasis 12 ± 7 cm) and 29 consecutive standard achalasia controls underwent therapy. Among cases, LES dysfunction was most often identified by RDC and/or barium esophagogram. Short-term symptomatic success was equivalent in cases vs controls (90% vs 93%; 95% CI for difference: -19% to 13%). Median short-term (1 vs 1; 95% CI for difference: 0-1) and long-term Eckardt scores (2 vs 1; 95% CI for difference: 0-2) were similar in cases and controls, respectively. Adequate clearance was observed in 67% of cases vs 81% of controls on post-therapy esophagogram. CONCLUSIONS AND INFERENCES: We described a subset of achalasia patients with normal IRP, but impaired LES relaxation identifiable only on additional provocative tests. These patients benefited from treatment, suggesting that such tests should be performed to increase the number of clinically relevant diagnoses.

Angle of His Accentuation Is a Viable Alternative to Dor Fundoplication as an Adjunct to Laparoscopic Heller Cardiomyotomy: Results of a Randomized Clinical Study.

BACKGROUND: There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM. METHODS: A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL. RESULTS: Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups. CONCLUSION: AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time. CLINICAL REGISTRATION NUMBER: CTRI: REF/2014/06/007146.

Esophageal achalasia: current diagnosis and treatment.

INTRODUCTION: Esophageal achalasia is a primary esophageal motility disorder of unknown origin, characterized by lack of peristalsis and by incomplete or absent relaxation of the lower esophageal sphincter in response to swallowing. The goal of treatment is to eliminate the functional obstruction at the level of the gastroesophageal junction. Areas covered: This comprehensive review will evaluate the current literature, illustrating the diagnostic evaluation and providing an evidence-based treatment algorithm for this disease. Expert commentary: Today, we have three very effective therapeutic modalities to treat patients with achalasia - pneumatic dilatation, peroral endoscopic myotomy, and laparoscopic Heller myotomy with fundoplication. Treatment should be tailored to the individual patient, in centers where a multidisciplinary approach is available. Esophageal resection should be considered as a last resort for patients who have failed prior therapeutic attempts.

Dysphagia Post Subcortical and Supratentorial Stroke.

BACKGROUND: Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. METHODS: Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. RESULTS: Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. CONCLUSION: Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA.

Low bone mineral density for age/osteoporosis in triple A syndrome-an overlooked symptom of unexplained etiology.

UNLABELLED: Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein alacrima achalasia adrenal insufficiency neurologic disorder (ALADIN). Our investigation suggests that low bone mineral density (BMD) for age/osteoporosis could be a common but overlooked symptom of unexplained etiology in this rare multisystemic disease. INTRODUCTION: The purpose of this study is to evaluate incidence and etiology of BMD for age/osteoporosis, a possibly overlooked symptom in triple A syndrome. METHODS: Dual-energy X-ray absorptiometry (DXA) of the femoral neck, total hip, lumbar spine, and radius, bone turnover markers, minerals, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), 1,25-dihydroxy vitamin D (1,25-OH2D), intact parathyroid hormone (PTH), and adrenal androgens (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) were measured in five male and four female patients. RESULTS: At time of diagnosis, low BMD for age was suspected on X-ray in seven of nine patients aged 2-11 years (not performed in two patients); normal levels of minerals and ALP were found in nine patients and low levels of adrenal androgens in eight patients (not measured in one patient). Reevaluation 5-35 years after introduction of 12 mg/m(2)/day hydrocortisone showed low BMD for age in two children, osteopenia in one, and osteoporosis in six adults. Normal levels of minerals, ALP, PTH, 1,25-OH2D, procollagen type 1, crosslaps, and osteocalcin were found in all patients. Low levels of adrenal androgens were found in all and 25OHD deficiency in six patients. Body mass index was <25 % for age and sex in eight of nine patients. CONCLUSION: Low BMD for age/osteoporosis in our patients probably is not a result of glucocorticoid therapy but could be the consequence of low level of adrenal androgens, neurological impairment causing physical inactivity, inadequate sun exposure, and protein malnutrition secondary to achalasia. Considering ubiquitous ALADIN expression, low BMD/osteoporosis may be a primary phenotypic feature of the disease. Besides optimizing glucocorticoid dose, physical activity, adequate sun exposure, appropriate nutrition, and vitamin D supplementation, therapy with DHEA should be considered.

Medical and surgical management of esophageal and gastric motor dysfunction.

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.

[Rehabilitation of the patients presenting with oesophageal achalasia following balloon cardiodilation].

The present study involved a total of 25 patients presenting with oesophageal achalasia who had undergone balloon cardiodilation. The complex of rehabilitative measures concluded the application of an ultrahigh-frequency electromagnetic fields (decimeter wave (DMW) therapy) to the collar region and general iodine bromide baths. The treatment resulted in the elimination of dysphagia syndrome during consumption of solid food in 80% of the patients. Simultaneously, the oesophagogastroscopic study revealed the improvement of the state of oesophageal mucosa. Moreover, the thyrotropin level was normalized. The positive effect of such rehabilitative treatment persisted during 6-8 months.

Esophageal motor disorders: achalasia and esophageal spasm.

PURPOSE: To define the esophageal motor disorders of achalasia and esophageal spasms and describe their presentation in the clinical setting. DATA SOURCES: Selected research-based articles, textbooks, and expert opinion. A case study is presented. CONCLUSIONS: The presentation of esophageal motor disorders may not be clear, particularly when the presenting symptom is chest pain. Determining whether the pain is cardiac or digestive in origin is crucial. IMPLICATIONS FOR PRACTICE: Progressive dysphagia for both solids and liquids is the major symptom of achalasia; other symptoms include regurgitation, chest pain, and nocturnal cough. Diffuse esophageal spasm typically causes substernal chest pain with nonprogressive dysphagia and odynophagia for both liquids and solids. Dysphagia related to esophageal motility is characterized by a sensation of swallowed food "sticking" in the throat or chest; there is no problem initiating the act of swallowing.

Treating achalasia: from whalebone to laparoscope.

OBJECTIVE: To review the pathophysiology and management of achalasia. DATA SOURCES: Peer-reviewed publications located via MEDLINE using the search term esophageal achalasia (subheadings: complications, drug therapy, epidemiology, etiology, physiopathology, surgery, and therapy) published in English from 1966 to December 1997. STUDY SELECTION: Of 2632 citations identified, 4.5% were selected for inclusion by authors' blinded review of the abstracts. New developments in the understanding of achalasia or reports of therapeutic efficacy in either controlled trials or uncontrolled consecutive series involving 10 patients or more observed for a year or longer were reviewed in detail. DATA EXTRACTION: All 6 controlled therapeutic trials were included, and therapeutic efficacy in uncontrolled series was assessed by the authors extracting the patients with a good-to-excellent response from each study and calculating a pooled estimate of response rate with individual studies weighted proportionally to sample size. DATA SYNTHESIS: Achalasia results from irreversible destruction of esophageal myenteric plexus neurons causing aperistalsis and failed lower sphincter relaxation. The only therapies that adequately compensate for this dysfunction for a sustained time are pneumatic dilation and Heller myotomy. The single controlled trial comparing these treatments found surgery superior to dilation (95% vs 51% nearly complete symptom resolution, P<.01). In uncontrolled trials pneumatic dilation (weighted mean [SD]) is 72% (26%) effective vs 84% (20%) for Heller myotomy. The limitation of dilation is a 3% risk of perforation; thoracotomy morbidity has been the major limitation of myotomy. Surgical morbidity has been sharply reduced by laparoscopic techniques. CONCLUSIONS: Both pneumatic dilation and surgical myotomy are effective therapies for achalasia; laparoscopic Heller myotomy is emerging as the optimal surgical therapy.

[Esophageal achalasia with apparently normal relaxation of the lower sphincter: clinical significance and therapeutic response to pneumatic dilatation]. / Acalasia esofágica con relajación aparentemente normal del esfínter inferior: significado clínico y respuesta terapéutica a la dilatación neumática.

OBJECTIVE: To evaluate if the clinical presentation and the response to pneumatic dilation is different in patients with achalasia with an apparent normal lower esophageal sphincter relaxation. DESIGN: Prospective study to compare clinical, radiographic and manometric characteristics and the response to pneumatic dilation according to the ability of the lower esophageal sphincter to relax normally. PATIENTS: One hundred and fifty seven consecutive patients with achalasia were included. Relaxation of the lower esophageal sphincter was abnormal in 130 patients and apparently normal in 27. The response to pneumatic dilation was evaluated in 116 patients, 94 with abnormal function of the lower esophageal sphincter and 22 with normal function. RESULTS: Clinical findings, esophageal diameter and basal pressure of the lower esophageal sphincter were similar in both groups. The efficacy of the dilation, the number of dilations and the rate of complications were also similar. CONCLUSIONS: Patients with achalasia and an apparent normal lower esophageal sphincter relaxation are not different from patients with typical achalasia and present a similar response to pneumatic dilation.

Isosorbide dinitrate or nifedipine: which is preferable in the medical therapy of achalasia?

Oesophageal motor activity was recorded manometrically with a low compliance system in 16 patients with achalasia and a slightly dilated oesophagus. After a basal recording period, nifedipine 20 mg was given sublingually to 9 patients and isosorbide dinitrate 5 mg to another 7 patients. Lower oesophageal sphincter pressure (LESp) and oesophageal body pressure wave amplitude were measured for 60 min after drug administration. Both drugs decreased LESp and pressure wave amplitude, but the effect of isosorbide dinitrate was faster and more intense than that of nifedipine. There was a lower inhibitory effect of nifedipine on the amplitude of pressure waves than on LESp, while isosorbide dinitrate inhibited with a similar intensity both LESp and pressure waves.

Return of esophageal peristalsis after nifedipine therapy in patients with idiopathic esophageal achalasia.

This study was carried out to demonstrate the possible return of esophageal peristalsis in patients affected by esophageal achalasia chronically treated with sublingual nifedipine and to investigate which parameters are correlated with the return of peristalsis. Thirty-two patients were treated with sublingual nifedipine 10-20 mg taken 30 min before meals. A clinical and manometric evaluation was performed before and after 6 months of therapy. Before treatment, in no patient was peristaltic activity recorded. After 6 months, peristalsis was observed in six patients. In this group, no pretreatment manometric parameter was different from that of the remaining achalasic patients; only the clinical history of dysphagia was significantly shorter (p < 0.001) and the esophageal diameter significantly less (p < 0.001). In conclusion, chronic treatment with sublingual nifedipine can induce a return of esophageal peristalsis in patients with a short clinical history of disease and slightly dilated esophagus.

Short report: comparison of the effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying in patients with Chagasic achalasia.

The effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying were compared in 11 patients with Chagasic achalasia. The oesophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique. No treatment preceded one of the studies (basal study). Nifedipine (20 mg) by the sublingual route 30 min before the meal, preceded one study. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded the third study. The order of the studies was allocated randomly for each patient. Oesophageal retention at the completion of the meal was significantly less (P less than 0.01) after isosorbide dinitrate (median: 54%, range: 5-87%) than after sublingual nifedipine (median: 78%, range: 7-99%) or after the control study (median: 83%, range: 5-100%). This difference persisted up to 20 min after the meal. Values measured in the control study and after sublingual nifedipine were not different (P greater than 0.10). These results show that isosorbide dinitrate, but not sublingual nifedipine, enhances oesophageal emptying in Chagasic achalasia.

Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia.

Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia.

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.

Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo.

Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.

Effect of transcutaneous nerve stimulation on esophageal motility in patients with achalasia and scleroderma.

It has been suggested that low-frequency transcutaneous electric nerve stimulation (TENS) alleviates the dysphagia produced by achalasia and scleroderma of the esophagus. The present study was conducted to elucidate whether TENS treatment improves dysphagia because of changes it induces on esophageal motility. We studied nine achalasia patients before forceful dilatation of the cardias, nine achalasia patients after dilatation, and nine patients with scleroderma. High-frequency TENS was applied to the hand for 30 min while esophageal motility was monitored by manometry. In none of the groups did TENS produce any change in the basal tone of the lower esophageal sphincter, lower esophageal sphincter relaxation, or esophageal body wave amplitude. Low-frequency TENS, used in another seven untreated achalasia patients, also did not improve esophageal motility. Our data indicate that high- or low-frequency TENS does not induce detectable changes in esophageal motility in patients with achalasia or scleroderma.

Quantitative assessment of the response to therapy in achalasia of the cardia.

Radionuclide oesophageal transit studies and manometry have been carried out in 15 patients with achalasia of the cardia, before treatment, after a course of nifedipine and after pneumatic bag dilatation. Transit studies were also done in 10 patients after cardiomyotomy and in 10 normal subjects. Images were recorded with the subjects seated in front of a gamma camera while swallowing a 10 ml bolus of 99Tcm-tin colloid and then after a further drink of 50 ml water. There was marked retention of tracer in the oesophagus in patients with achalasia compared with rapid clearance in control subjects. Bag dilatation significantly reduced lower oesophageal sphincter pressure but there was no significant difference in the 50% clearance time or percentage dose retained at 100s before and after the treatments. Oesophageal clearance of tracer after the additional drink of water, was improved by bag dilatation. Oesophageal transit in the patients after cardiomyotomy was similar to that in patients who had undergone bag dilatation. There was considerable retention of the tracer in the oesophagus overnight, but this did not result in pulmonary aspiration. Radionuclide oesophageal transit studies provided a quantitative assessment of therapy in achalasia and the proportion of tracer retained after the additional drink proved to be a sensitive measure of response to treatment. Nifedipine proved ineffective as a treatment for achalasia. Bag dilatation and cardiomyotomy were of similar value.