An Immunohistochemical Study of the Myenteric Plexus in Idiopathic Achalasia

Villanacci, Vincenzo; Annese, Vito; Cuttitta, Antonello; Fisogni, Simona; Scaramuzzi, G.; Santo, Ermelinda De; Corazzi, Nadia; Bassotti, Gabrio

doi:10.1097/mcg.0b013e3181bc9ebf

Cited by 54 publications

(40 citation statements)

References 34 publications

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“…The finding of a predominance of CD3+/CD8+ lymphocytes in specimens that had an inflammatory infiltrate confirms findings of previous studies [19, 20]. This subset of patients with an inflammatory infiltrate surrounding ganglion cells and/or neurons represents a subgroup of patients for which future studies of immunotherapy may be attempted, possibly targeted at cytotoxic T cells.…”

Section: Discussionsupporting

confidence: 89%

Histopathologic patterns among achalasia subtypes

Sodikoff

Shetuni

et al. 2015

Neurogastroenterology Motil

107

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Background Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns. Methods We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by 2 expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes. Key Results Manometry studies were categorized as follows: type I (n=20), type II (n=20), type III (n=3), and esophagogastric junction outflow obstruction (EGJOO) (n=3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs. 13/20, p=0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p=0.016). CD3+/CD8+ cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO). Conclusions and Inferences The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings – from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology – emphasizes that ‘achalasia’ represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.

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Section: Discussionsupporting

confidence: 89%

Histopathologic patterns among achalasia subtypes

Sodikoff

Shetuni

et al. 2015

Neurogastroenterology Motil

107

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“…Although data from correlation analyses should not be interpreted as causative, those data in conjunction with data from previous studies suggest that alterations in both nitrergic innervation and ICC density may be viewed as inter-dependent events. A decrease in ICCs density in the muscle layers has been associated with reduction of the NO-dependent inhibitory response [33] and several other studies in the literature have implicated ICCs in NO-dependent neurotransmission [11,18,29,34]. Moreover, NO is considered to be a cytoprotective molecule that affects the survival of the ICCs [35,36].…”

Section: Discussionmentioning

confidence: 99%

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

Nascimento¹,

Martins²,

Duarte³

et al. 2017

Int J Pathol Clin Res

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The pathogenesis of megaesophagus in chronic Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi is compelling. Individuals with megaesophagus often present achalasia and disturbances of peristalsis and neuronal loss. Esophageal samples were obtained from 6 T. cruzi infected individuals with megaesophagus, 6 T. cruzi infected individuals without megaesophagus, and 6 noninfected individuals who underwent necropsy procedures. Using one antibody specific for neuronal Nitric Oxide Synthase (nNOS) and another specific for Protein Gene Product 9.5 (PGP-9.5), which is a pan-neuronal marker, we demonstrated the relative area of nitrergic innervation. Additionally, we analysed the area occupied by Interstitial Cells of Cajal (ICCs) with antibody specific anti-CD117. The analyses presented here show that the relative area of nitrergic innervation is reduced in T. cruzi infected individuals with megaesophagus. Furthermore, we demonstrated reduced CD117-immunostained areas in the esophagus of T. cruzi infected individuals. Statistical analyses revealed a positive correlation between the relative area of nitrergic innervation and the density of ICCs in the same infected individuals. Considering data from the literature, we raised the hypothesis that the loss of nitrergic nerve fibers and ICCs could be view as an interdependent phenomenon occurring in the esophagus of T. cruzi infected individuals and that it could contribute to peristalsis disturbances, to achalasia and to megaesophagus development.

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“…The degenerating neurons and ganglia are often surrounded by lymphocytes and eosinophils; therefore, an autoimmune hypothesis has been formulated [5][6][7].…”

Section: Discussionmentioning

confidence: 99%

Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES Correlated with Type of Fundoplication

et al. 2017

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Objective: The aim of the present study is to show the predictive value of the preoperative resting pressure of the lower esophageal sphincter (LES) correlated with the type of fundoplication (Nissen or Dor) after Heller myotomy in our series. Materials and Methods:From January 1998 to June 2010, 88 patients affected by esophageal achalasia underwent surgery at our unit. However, our study focused on a sample of 36 patients, because many data were lost or was never recorded. Among these, 14 patients underwent laparoscopic Heller myotomy plus Nissen fundoplication (group N), whereas 22 patients underwent laparoscopic Heller myotomy plus Dor fundoplication (group D). Clinical evaluation was performed using a modified DeMeester symptom scoring system consisting of the assessment of three symptoms: dysphagia, regurgitation, and heartburn. To each symptom was assigned a score from 0 to 3, depending on its severity, and the reduction in the severity of each symptom after surgery was assessed.Results: The surgical treatment is considered to be effective (p<0.0001). The preoperative resting pressures of LES were compared by Student's t-test, and it was found that patients who reported a greater improvement in the dysphagia symptom had a preoperative average pressure of LES that was significantly higher than that in other patients in both group N (p=0.03) and group D (p=0.01; p=0.003; p=0.001). The Dor treatment was shown to be more effective than the Nissen treatment (p<0.0001). Conclusion:The preoperative resting pressure of LES is a predictive factor of surgical success both before Dor fundoplication and before Nissen fundoplication, but its predictive power is influenced by the chosen type of fundoplication.Keywords: Achalasia, dysphagia, preoperative resting pressure of LES, predictive factors, fundoplication ÖZ Amaç: Bu çalışmanın amacı, serimizdeki Heller miyotomi sonrasında, funduplikasyon türü (Nissen veya Dor) ile ilişkili olarak alt özofageal sfinkterin (AÖS) preoperatif istirahat basıncının prediktif değerini göstermektir.Gereç ve Yöntem: Ocak 1998 ile Haziran 2010 arasında, özofageal akalazyadan etkilenen 88 hasta birimimizde ameliyat oldular. Ancak çalışmamızda, birçok verinin kaybolmasından veya hiç kaydedilmemiş olmasından dolayı, 36 hastaneden oluşan bir örnekleme odaklanıldı. Bu hastalardan 14'üne laparoskopik Heller miyotomi+Nissen fundoplikasyon (N grubu) uygulanırken, 22'sine laparoskopik Heller miyotomi+Dor fundoplikasyon (D grubu) uygulandı. Klinik değerlendirme, disfaji, regürjitasyon ve mide yanması olan üç semptomun değerlendirilmesini içeren modifiye DeMeester semptom skorlama sistemi kullanılarak yapıldı. Her bir semptoma 0 ile 3 arası bir puan verildi ve ameliyat sonrası her semptomun şiddetindeki azalma değerlendirildi.Bulgular: Cerrahi tedavinin etkili olduğu düşünülmektedir (p<0,0001). Ameliyat öncesi AÖS istirahat basınçları Student's t-test ile karşılaştırıldı. Disfaji semptomunda gelişme görülen hastalarda ameliyat öncesi ortalama AÖS basıncı, N grubu (p=0,03) ve D grubundaki (p...

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An Immunohistochemical Study of the Myenteric Plexus in Idiopathic Achalasia

Abstract: The enteric nervous system of the lower esophageal sphincter area is impaired in patients with "idiopathic achalasia," and the abnormalities involve ICC and neurons in many patients. The triggering factors for these abnormalities are, however, still unknown.

Cited by 54 publications

References 34 publications

Histopathologic patterns among achalasia subtypes

Histopathologic patterns among achalasia subtypes

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES Correlated with Type of Fundoplication

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