Spectrum of histopathologic findings in patients with achalasia reflects different etiologies
ABSTRACT 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.
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.
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.
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.
DMW - Deutsche Medizinische Wochenschrift 08/2006; 131(33):1799-1802. DOI:10.1055/s-2006-949156 · 0.55 Impact Factor
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ABSTRACT: Moyamoya is a cerebrovascular condition characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and the compensatory development of abnormal "moyamoya" vessels. The pathophysiological mechanisms of this condition, which leads to ischemic and hemorrhagic stroke, remain unknown. It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes). Here, we describe an autosomal-recessive disease leading to severe moyamoya and early-onset achalasia in three unrelated families. This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the α1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet analysis showed a complete loss of the soluble α1β1 guanylate cyclase and showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP pathway is a major pathway controlling vascular smooth-muscle relaxation, vascular tone, and vascular remodeling. Our data suggest that alterations of this pathway might lead to an abnormal vascular-remodeling process in sensitive vascular areas such as ICA bifurcations. These data provide treatment options for affected individuals and strongly suggest that investigation of GUCY1A3 and other members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset achalasia and nonsyndromic moyamoya.The American Journal of Human Genetics 02/2014; 94(3). DOI:10.1016/j.ajhg.2014.01.018 · 10.99 Impact Factor
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ABSTRACT: Oesophagus is a muscular tube that transports food and liquidsby coordinated contraction of its muscular lining led by stimuli from the nerveplexus. Its muscularis proper layer consists of muscle cells, connective tissue andmyenteric plexus. The aim of our histomorphometric study was to reveal detailedcharacteristics of this layer, cell number, volume, orientation, properties of myentericplexus as well as changes related to aging. Oesophagus tissue samples from 17 male cadavers weretaken from the cranial and thoracic parts. Samples were divided in 2 groups: younger(ages 21-45) and older (ages 66-78). The tissue was routinely processed,embedded and serially sectioned. Sections were stained with Masson-Goldner andCresyl-violet dyes. Digital images were analysed with the image analysis software.Statistics were performed with SPSS software. The average thickness of the cranial part of the oesophageal wall andmuscularis proper was 2590 μm and 1197 μm, respectively in the younger and2453 μm and 1144 μm in the older group. Overall volume of the muscle tissuewas slightly larger in the thoracic part, and in the younger group comparedto the cranial part and the older group. The average number of the striatedmuscle cells per 100 μm in the cranial part was 771.5 and 749.7 in the youngerand the older group, respectively. Striated cells were significantly lesspresent only in the lower thoracic part of the oesophagus. In the older group,smaller striated muscle cells dominated over the larger ones. In the youngergroup, majority of the striated muscle cells were mid-sized. The thickness ofthe circular layer of muscularis proper was more affected by aging than thelongitudinal one. Ganglion cells number was lower in the older group, butplexus area was unchanged. Aging affects muscularis proper and myenteric plexus of the oesophagus.Major differences can be observed in the striated muscle cells size, volumeof the circular layer and number of the ganglionic cells in the myenteric plexus.Folia morphologica 08/2013; 72(3):223-9. DOI:10.5603/FM.2013.0037 · 0.52 Impact Factor