Ganglioneuromatosis is a rare type of benign neurogenic tumor that usually affects the sites of the major sympathetic ganglia in the retroperitoneum and the posterior mediastinum. Affection of the gastrointestinal tract is rare, and involvement of the esophagus is exceptional. To the best of our knowledge, only 4 cases of esophageal ganglioneuromatosis in adults were reported in the literature. No cases have been reported in the pediatric age group.

An 11-year-old boy presented with dysphagia due to severe esophageal stenosis caused by esophageal ganglioneuromatosis.

Despite its rarity, the present case implies that ganglioneuromatosis should be considered in children with idiopathic esophageal stenosis.

Esophagogastroduodenoscopy (EGD) is performed to rule out organic diseases in the diagnosis of esophageal motility disorders (EMDs). Abnormal endoscopic findings can be observed during EGD, which indicate the presence of EMDs. Several endoscopic findings at both the esophagogastric junction and esophageal body that are related to EMDs have been reported. Gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) could be detected during EGD, and these diseases are often associated with abnormal esophageal motility. Image-enhanced endoscopy (IEE) could improve the detection of these diseases during EGD. Although no report has been published previously on the potential usefulness of IEE in the endoscopic diagnosis of EMDs, IEE can be used to detect disorders that can be associated with abnormal esophageal motility.

A variety of esophageal pathologies can present emergently with a chief complaint of acute chest pain. Computed tomography (CT) is often the first line of imaging in esophageal emergencies and provides useful information-even without an initial suspicion-when used in conjunction with other imaging modalities such as esophagography and direct visualization. We review various urgent and emergent esophageal disease entities which may manifest as acute chest pain, with an emphasis on CT and ancillary imaging appearances, while discussing management according to their emergency. Radiologists should be familiar with the imaging findings of these esophageal emergencies in order to provide an accurate diagnosis and recommend timely and appropriate management.

Achalasia is an uncommon disorder that results from the degeneration of ganglion cells of the myenteric plexus in the lower esophageal wall. It is manifested by a loss of peristalsis in the lower part of the esophagus and failure of the lower esophageal sphincter (LES) to relax. Peroral endoscopic myotomy (POEM) is a minimally invasive intervention that aims to treat achalasia. It is regarded as the endoscopic equivalent of Heller myotomy. POEM is a form of natural orifice transluminal endoscopic surgery that is completed by creating a submucosal tunnel in the lower part of esophagus to reach the inner circular muscle bundles of the LES to perform myotomy, while preserving the outer longitudinal muscle bundles. The result is decreased resting pressure of the LES, facilitating the passage of ingested material. POEM was initially introduced to treat achalasia by targeting the LES. POEM has expanded to include gastric POEM (G-POEM), myotomy of the pyloric sphincter to treat gastroparesis, and per rectal endoscopic myotomy to treat adult Hirschsprung's disease.

Peroral endoscopic myotomy surgery is an incisionless, minimally invasive, natural orifice technique used to treat the symptoms of achalasia and other spastic disorders of the esophagus. Recent experience demonstrates that it can be performed safely by experienced esophageal surgeons and there are very good short-term outcomes comparable to laparoscopic myotomy. The rapid worldwide adoption of this technique demonstrates its potential to replace the current therapies available for achalasia. A cautionary note is important in that long-term outcomes are not yet available in terms of dysphagia and GERD symptoms.

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome.

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and has widely variable expressivity. Oral manifestations are common, but there are no studies that investigated functional alterations in salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1 individuals, comparing to a control group, and to investigate the possible causes and some consequences of salivary gland alteration.

This is a case-control study that evaluated the salivary flow rate of NF1 individuals (n = 49) and compared to an age and sex-matched control group. We have also investigated the possible causes and consequences of hyposalivation in NF1 individuals through anamnesis, a specific questionnaire, physical examination, tongue coating evaluation and cytopathological exam to assess the prevalence of oral candidiasis.

Hyposalivation at rest was present in 59% (29/49) of NF1 individuals in contrast to 22% (11/49) in the control group, being statistically significant (P <0.0001; Wilcoxon rank-sum test). The analysis of the adjusted residual showed that the prevalence of hyposalivation in NF1 individuals (46.9%) was 4-fold higher than in controls (10.2%). None of the possible causes of hyposalivation (medications, low liquid intake, caffeinated or stimulant drink use, mouth breathers, alcohol, smoke and plexiform neurofibroma close to or involving major salivary glands areas) had important impact on the salivary flow rate in NF1 individuals.

Hyposalivation may be a consequence of NF1, as occurs in other genetic diseases. More studies are necessary to understand if there is and what is the relationship between NF1 and hyposalivation.

The current state of research into the etiology of achalasia only allows for speculation. To date, several studies have been performed investigating genetic, immune, and infectious disease mechanisms; however, none of these have been conclusive. Further research into this topic is warranted given the severity of the disease, and it may be possible that all of these mechanisms are involved in the pathophysiology of the disease.

Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed in achalasia patients. The candidate gene approach has revealed some promising results; however, it has not established conclusive links to specific genes so far. The aim of this review was to summarize current knowledge of the genetics of achalasia. We also discuss the extent to which our understanding of achalasia is likely to be enhanced through future molecular genetic research.

Despite increasing understanding of the pathophysiology of achalasia, the etiology of this esophageal motility disorder remains largely unknown. However, the occurrence of familial achalasia and its association with well-defined genetic syndromes suggest the involvement of genetic factors. Mutant mouse models display gastrointestinal disturbances that are similar to those observed in achalasia patients. The candidate gene approach has revealed some promising results; however, it has not established conclusive links to specific genes so far. The aim of this review was to summarize current knowledge of the genetics of achalasia. We also discuss the extent to which our understanding of achalasia is likely to be enhanced through future molecular genetic research.

There have been previous reports suggesting an association between von Recklinghausen's neurofibromatosis and esophageal dysmotility. We report the first case of true Recklinghausen's neurofibromatosis of the esophagus leading to end-stage pseudoachalasia. The diagnosis and management of this condition is discussed together with the pathogenesis and pathology of this rare entity.

Idiopathic achalasia is an inflammatory disease of unknown etiology characterized by esophageal aperistalsis and failure of LES relaxation due to loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Proposed causes of achalasia include gastroesophageal junction obstruction, neuronal degeneration, viral infection, genetic inheritance, and autoimmune disease. Current evidence suggests that the initial insult to the esophagus, perhaps a viral infection or some other environmental factor, results in myenteric plexus inflammation. The inflammation then leads to an autoimmune response in a susceptible population who may be genetically predisposed. Subsequently, chronic inflammation leads to destruction of the inhibitory myenteric ganglion cells resulting in the clinical syndrome of idiopathic achalasia. Further studies are needed to better understand the etiology and pathogenesis of achalasia-such an understanding will be important in developing safe, effective, and possibly curative therapy for achalasia.

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.

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.

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%).

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.

Secondary achalasia or pseudoachalasia is mostly caused by gastric or oesophageal carcinoma. Here we report a case of pseudoachalasia caused by a pancreatic tumour invading the cardiac region. A 66-year-old man with a 2-month history of dysphagia and weight loss showed no abnormalities on upper gastrointestinal endoscopy and computed tomography scan, but had no swallow-induced relaxation on oesophageal manometry. Based on the patient's history and oesophageal manometry findings, further investigation was performed to exclude pseudoachalasia. Endoscopic ultrasonography showed abnormalities in the cardiac region, but large endoscopic biopsies showed no malignancy. A laparotomy was performed, which revealed a large, irresectable tumour originating from the pancreatic corpus region and expanding into the gastric cardia region. This case illustrates that a pancreatic tumour invading the cardiac region may present as pseudoachalasia.

A case report is presented of a 59-year-old woman who was suspected of having a paraesophageal hernia, but at operation was found to have an epiphrenic diverticulum of the esophagus, a benign stromal tumor of the esophagus, and pseudoachalasia. The stromal tumor was resected laparoscopically together with a laparoscopic Heller's myotomy and partial posterior fundoplication.

Achalasia is a rare but important condition affecting the myenteric neurons of the esophagus. A number of studies have provided evidence for the preservation of cholinergic innervation to the esophagus in achalasia. This forms the rationale for the treatment of achalasia with botulinum toxin. Identification of nitric oxide as the primary inhibitory neurotransmitter of the gastrointestinal tract has improved our understanding of the pathophysiology of primary achalasia. Neurons containing nitric oxide are absent within the myenteric plexuses of patients with achalasia, and the experimental inhibition of nitric oxide produces a picture that manometrically mimics achalasia. Recent advances have provided insights into the genetic basis and pathogenesis of a growing number of secondary forms of achalasia. Examples of such secondary disorders include Allgrove's syndrome, autoimmune polyglandular syndrome, and multiple endocrine neoplasia type 2B.

A 21 year old man with type 1 neurofibromatosis was found dead in the middle of the night. Postmortem examination revealed a large neurofibroma arising from the right intrathoracic vagus nerve, which might have contributed to his sudden death.

Achalasia is an uncommon esophageal motility disorder of unknown etiology. To gain insights into possible etiologic risk factors, demographic and comorbidity data were obtained from Medicare hospital discharge data files from 1986-1989 on patients aged 65 and older. Age-adjusted sex- and race-specific occurrence rates were calculated for each US state. The rate of comorbid illness occurrence in achalasia patients was compared to that of the entire hospitalized Medicare population. Records of 15,000 achalasia discharges were available for analysis. Achalasia discharge rates increased linearly from age 65 to 94 years. They were similar in males and females as well as whites and nonwhites. High rates were observed in the South and low rates in most states of the East North Central region around the Great Lakes and in the Pacific region. The same geographic pattern was observed in men and women as well as in the two separate subsets of data representing the periods 1986-1987 and 1988-1989. Achalasia was associated with a significantly increased risk for pulmonary complications, malnutrition, and gastroesophageal cancer. The concordant occurrence of achalasia in patients with Parkinson's disease, depressive disorder, and various other myoneural disorders indicated a possible etiologic relationship. Achalasia appears to represent the clinical end point of several different pathways. Besides aging, different neurologic diseases may contribute to a loss in control of esophageal motility. The geographic pattern could suggest the influence of environmental factors.

A man with known systemic neurofibromatosis developed an acute upper gastrointestinal hemorrhage while hospitalized after a neurosurgical procedure. Endoscopic evaluation showed a vascular lesion with an appearance consistent with a Dieulafoy-type lesion in the distal esophagus. Despite multiple endoscopic procedures with attempted coagulation of the bleeding lesion, the patient continued to have life-threatening hemorrhaging. At thoractomy, a tumor was found to arise from the vagus nerve at the site of bleeding. This tumor was resected and histologically determined to be a neurilemoma. Acute bleeding into the esophagus associated with this type of tumor has not been previously reported.

Gastrointestinal involvement in von Recklinghausen's disease occurs in three principal forms: hyperplasia of the submucosal and myenteric nerve plexuses and mucosal ganglioneuromatosis which leads to disordered gut motility; gastrointestinal stromal tumours showing varying degrees of neural or smooth muscle differentiation; and a distinctive glandular, somatostatin-rich carcinoid of the periampullary region of the duodenum that contains psammoma bodies and which may be associated with phaeochromocytoma. This review describes the histopathological features of these lesions and discusses potential pitfalls in their differential diagnosis. Their accurate identification has significant implications for clinical management and may even provide the first pointer to the diagnosis of neurofibromatosis.

Neurologic diseases can affect the bowel at several levels of innervation--by altering the electrical activity that controls smooth muscle, the enteric nervous system, or the extrinsic neural pathways to the gut. This review concentrates on disorders of motility that occur in conjunction with diseases of the extrinsic neural supply (from the level of the brain to the postganglionic fibers) and those generalized disorders that affect gut smooth muscle. Modern technology, such as gastrointestinal scintigraphy and manometric techniques that measure esophageal, gastroduodenal, and anorectal motility (intraluminal pressures), has provided better methods to study the pathophysiologic aspects of gut motility in diseases of the nervous system. Distinguishing the neuropathies of the extrinsic nervous system from those of the intrinsic (enteric) nervous system is not always possible because the available techniques evaluate only the end-organ--that is, the motor function of the gut. Degenerative or infiltrative (myopathic) disorders of gut smooth muscle, however, can be distinguished from such neuropathies, and careful and systematic evaluation of autonomic function can often identify the level of disordered function in the neural-gut axis.

Although achalasia is usually of idiopathic origin, it may be secondary to another disease process such as neoplasia. The first description of a familial achalasia syndrome that appears to be secondary to diffuse esophageal leiomyomatosis with entrapment of nerve ganglia is presented. Documented in four generations of a family, the disease followed an autosomal dominant mode of inheritance. Long lower esophageal sphincter pressure zones and a high incidence of epiphrenic diverticula were interesting accompaniments of achalasia in this family. Many achalasia-affected family members have also had associated intestinal leiomyomas or neurofibromas. Affected family members also had urticaria pigmentosa, and some had systemic mast cell disease as well.