Evaluation of the immunoreactivity of nerve growth factor and tropomyosin receptor kinase A in the esophagus of noninfected and infected individuals with Trypanosoma cruzi.

Megaesophagus is one of the major manifestations of the chronic phase of Chagas disease. Its primary symptom is generally dysphagia due to disturbance in the lower esophageal sphincter. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we evaluated the immunoreactivity of nerve growth factor (NGF), and of its receptor tropomyosin receptor kinase A (TrkA), molecules that are well known for having a relevant role in neuroimmune communication in the gastrointestinal tract. Esophageal samples obtained via autopsy or surgery procedures from six noninfected individuals, six infected individuals without megaesophagus, and six infected individuals with megaesophagus were analyzed. Infected individuals without megaesophagus presented increased numbers of NGF immunoreactive (IR) mast cells and increased areas of TrkA-IR epithelial cells and inner muscle cells. Infected individuals with megaesophagus showed increased numbers of NGF-IR eosinophils and mast cells, TrkA-IR eosinophils and mast cells, increased area of NGF-IR epithelial cells, and increased areas of TrkA-IR epithelials cells and inner muscle cells. The data presented here point to the participation of NGF and its TrkA receptor in the pathology of chagasic megaesophagus.

Trypanosoma cruzi Detection in Colombian Patients with a Diagnosis of Esophageal Achalasia.

Achalasia is a motility disorder of the esophagus that might be secondary to a chronic Trypanosoma cruzi infection. Several studies have investigated esophageal achalasia in patients with Chagas disease (CD) in Latin America, but no related studies have been performed in Colombia. The goals of the present study were to determine the presence of anti-T. cruzi antibodies in patients with esophageal achalasia who visited a referral hospital in Bogotá, Colombia, and to detect the presence of the parasite and its discrete typing units (DTUs). This cross-sectional study was conducted in adult patients (18-65 years old) who were previously diagnosed with esophageal achalasia and from whom blood was drawn to assess antibodies against T. cruzi using four different serological tests. Trypanosoma cruzi DNA was detected by conventional polymerase chain reaction (cPCR) and quantitative polymerase chain reaction (qPCR). In total, 38 patients, with an average age of 46.6 years (standard deviation of ±16.2) and comprising 16 men and 22 women, were enrolled. Five (13.15%) patients were found to be positive for anti-T. cruzi antibodies by indirect immunofluorescence assay (IFA), and two patients who were negative according to IFA were reactive by both enzyme-linked immunosorbent assay and immunoblot (5.3%). Parasite DNA was detected in two of these seven patients by cPCR and in one of these by qPCR. The parasite DTU obtained was TcI. In summary, this study identified T. cruzi in Colombian patients with esophageal achalasia, indicating that digestive compromise could also be present in patients with chronic CD.

Compromiso gastrointestinal por Triypanosoma cruzi: ¿cuándo buscar y cuándo tratar? / Digestive involvement by Trypanosoma cruzi: when to look for it and when to treat

Chagas disease is an endemic zoonosis that can cause chronic medical complications in a third of those infected, usually decades after infection. It mainly affects the peripheral nervous system of heart, esophagus and colon. At digestive level, motor dysfunction leads to the development of megaesophagus and megacolon whose predominant symptoms are dysphagia and constipation. It should be suspected in patients with epidemiological history and compatible symptoms. In the chronic phase it is confirmed with the detection of specific antibodies. The etiological treatment is effective in early stages after infection. In the chronic stage the management is symptomatic, medical and/or surgical.

La enfermedad de Chagas es una zoonosis endémica que puede producir complicaciones médicas crónicas en un tercio de los infectados, habitualmente décadas luego de la infección. Afecta principalmente el sistema nervioso periférico de corazón, esófago y colon. A nivel digestivo la disfunción motora lleva a la formación de megaesófago y megacolon cuyos síntomas predominantes son disfagia y constipación. Debe sospecharse en pacientes con antecedentes epidemiológicos y síntomas compatibles. En la fase crónica se confirma con la detección de anticuerpos específicos. El tratamiento etiológico es efectivo en las fases tempranas post-contagio. En la etapa crónica el manejo es sintomático, médico y/o quirúrgico.

Prevalence of Trypanosoma cruzi and organ alterations in Virginia opossums (Didelphis virginiana) from western Mexico - short communication.

Small populations of Virginia opossum (Didelphis virginiana) in western Mexico are endangered by hunting and natural predators as well as by different kinds of diseases. After two serological analyses using Serodia® latex particle agglutination and indirect haemagglutination (IHA) tests, 35 (53.03%) of 66 collected opossums in two small towns in western Mexico were positive for the presence of Trypanosoma cruzi. Twenty-eight of the 35 seropositive opossums had pathological lesions: 11 had changes in only one organ, 13 in two organs, and four had pathological changes in three organs. Splenomegaly was the most common finding in the examined opossums, followed by hepatomegaly. These potentially fatal pathological changes could contribute to the scarcity of the opossum population, even leading to the extinction of this species in western Mexico.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

High-resolution manometry classifications for idiopathic achalasia in patients with Chagas' disease esophagopathy.

BACKGROUND: Idiopathic achalasia (IA) and Chagas' disease esophagopathy (CDE) share several similarities. The comparison between IA and CDE is important to evaluate whether treatment options and their results can be accepted universally. High-resolution manometry (HRM) has proved a better diagnostic tool compared to conventional manometry. This study aims to evaluate HRM classifications for idiopathic achalasia in patients with CDE. METHODS: We studied 98 patients: 52 patients with CDE (52 % females, mean age, 57 ± 14 years) and 46 patients with IA (54 % females; mean age 48 ± 19 years). All patients underwent a HRM and barium esophagogram. RESULTS: The Chicago classification was distributed in IA as Chicago I, 35 %; Chicago II, 63 %; and Chicago III, 2 %, and in CDE as Chicago I, 52 %; Chicago II, 48 %; and Chicago III, 0 % (p = 0.1, 0.1, and 0.5, respectively). All patients had the classic Rochester type. CDE patients had more pronounced degrees of esophageal dilatation (p < 0.002). The degree of esophageal dilatation did not correlate with Chicago classification (p = 0.08). In nine (9 %) patients, the HRM pattern changed during the test from Chicago I to II. CONCLUSION: Our results show that (a) HRM classifications for IA can be applied in patients with CDE and (b) HRM classifications did not correlate with the degree of esophageal dilatation. HRM classifications may reflect esophageal repletion and pressurization instead of muscular contraction. The correlation between manometric findings and treatment outcomes for CDE needs to be answered in the near future.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs.

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Current epidemiological profile of Chagasic megaesophagus in Central Brazil.

INTRODUCTION: Chagasic megaesophagus (CM) is the most common digestive manifestation of Chagas disease in Brazil, and the State of Goiás is one of the most affected regions. In recent decades, the Hospital das Clínicas (HC)/Universidade Federal de Goiás (UFG) has been a reference center for the study and treatment of CM. The objective of this study was to characterize the current epidemiological profile of patients with CM observed at the HC of the UFG from 1998 to 2010. METHODS: In total, 939 patient records were analyzed, and age, gender, place of birth, serology, symptoms and radiological classification according to Rezende et al. were analyzed. RESULTS: The median patient age was 55 years. Male patients were more (54%) prevalent than female patients. The prevalence of younger patients (less than 31 years of age) was 4.2%, but 82.1% of the younger patients were from State of Bahia. Patients older than 40 years were the majority (85.5%). The radiological groups were distributed as follows: Group I (35.9%), Group II (32.9%), Group III (17%) and Group IV (14.2%). CONCLUSIONS: Compared with previous studies by the same group in 1975, 1994 and 1995, the number of younger patients decreased, and the frequency curve has shifted to older patients.

Current epidemiological profile of Chagasic megaesophagus in Central Brazil

Introduction Chagasic megaesophagus (CM) is the most common digestive manifestation of Chagas disease in Brazil, and the State of Goiás is one of the most affected regions. In recent decades, the Hospital das Clínicas (HC)/Universidade Federal de Goiás (UFG) has been a reference center for the study and treatment of CM. The objective of this study was to characterize the current epidemiological profile of patients with CM observed at the HC of the UFG from 1998 to 2010. Methods In total, 939 patient records were analyzed, and age, gender, place of birth, serology, symptoms and radiological classification according to Rezende et al. were analyzed. Results The median patient age was 55 years. Male patients were more (54%) prevalent than female patients. The prevalence of younger patients (less than 31 years of age) was 4.2%, but 82.1% of the younger patients were from State of Bahia. Patients older than 40 years were the majority (85.5%). The radiological groups were distributed as follows: Group I (35.9%), Group II (32.9%), Group III (17%) and Group IV (14.2%). Conclusions Compared with previous studies by the same group in 1975, 1994 and 1995, the number of younger patients decreased, and the frequency curve has shifted to older patients. .

Laparoscopic Heller myotomy and fundoplication in patients with Chagas' disease achalasia and massively dilated esophagus.

Laparoscopic Heller myotomy and fundoplication is considered today the treatment of choice for achalasia. The optimal treatment for end-stage achalasia with esophageal dilation is still controversial. This multicenter and retrospective study aims to evaluate the outcome of laparoscopic Heller myotomy in patients with a massively dilated esophagus. Eleven patients (mean age, 56 years; 6 men) with massively dilated esophagus (esophageal diameter greater than 10 cm) underwent a laparoscopic Heller myotomy and anterior fundoplication between 2000 and 2009 at three different institutions. Preoperative workup included upper endoscopy, esophagram, and esophageal manometry in all patients. Average follow-up was 31.5 months (range, 3 to 60 months). Two patients (18%) had severe dysphagia, four patients (36%) had mild and occasional dysphagia to solid food, and five patients (45%) were asymptomatic. All patients gained or kept body weight, except for the two patients with severe dysphagia. Of the two patients with severe dysphagia, one underwent esophageal dilatation and the other a laparoscopic esophagectomy. They are both doing well. Heller myotomy relieves dysphagia in the majority of patients even when the esophagus is massively dilated.

Advanced megaesophagus (Group III) secondary to vector-borne Chagas disease in a 20-month-old infant.

The authors report the case of a female infant with Group III (or Grade III) megaesophagus secondary to vector-borne Chagas disease, resulting in severe malnutrition that reversed after surgery (Heller technique). The infant was then treated with the antiparasitic drug benznidazole, and the infection was cured, as demonstrated serologically and parasitologically. After follow-up of several years without evidence of disease, with satisfactory weight and height development, the patient had her first child at age 23, in whom serological tests for Chagas disease yielded negative results. Thirty years after the initial examination, the patient's electrocardiogram, echocardiogram, and chest radiography remained normal.

Advanced megaesophagus (Group III) secondary to vector-borne Chagas disease in a 20-month-old infant / Lactente de um ano e oito meses de idade com megaesôfago (Grupo III) por doença de Chagas adquirida vetorialmente

The authors report the case of a female infant with Group III (or Grade III) megaesophagus secondary to vector-borne Chagas disease, resulting in severe malnutrition that reversed after surgery (Heller technique). The infant was then treated with the antiparasitic drug benznidazole, and the infection was cured, as demonstrated serologically and parasitologically. After follow-up of several years without evidence of disease, with satisfactory weight and height development, the patient had her first child at age 23, in whom serological tests for Chagas disease yielded negative results. Thirty years after the initial examination, the patient's electrocardiogram, echocardiogram, and chest radiography remained normal.

Os autores relatam um caso de lactente com megaesôfago do Grupo III por doença de Chagas vetorialmente adquirida, responsável por acentuada desnutrição, da qual se recuperou com a cirurgia de Heller. Submetida em seguida a tratamento da infecção chagásica com benzonidazol, logrou cura, parasito e sorologicamente demonstrada. Seguiram-se anos sem qualquer incidente, com desenvolvimento pondo-estatural normal. Teve seu primeiro filho aos 23 anos, em quem as provas sorológicas para doença de Chagas resultaram negativas. Decorridos 30 anos após o atendimento inicial, continuava com eletrocardiograma e ecocardiograma e/ou exame radiológico do coração normais.

High resolution manometric findings in patients with Chagas' disease esophagopathy.

OBJECTIVE: To describe high resolution manometry features of a population of symptomatic patients with Chagas' disease esophagopathy (CDE). METHODS: Sixteen symptomatic dysphagic patients with CDE [mean age (54.81±13.43) years, 10 women] were included in this study. All patients underwent a high resolution manometry. RESULTS: Mean lower esophageal sphincter (LES) extension was (3.02±1.17) cm with a mean basal pressure of (15.25±7.00) mmHg. Residual pressure was (14.31±9.19) mmHg. Aperistalsis was found in all 16 patients. Achalasia with minimal esophageal pressurization (type 1) was present in 25% of patients and achalasia with esophageal compression (type 2) in 75%, according to the Chicago Classification. Upper esophageal sphincter (UES) mean basal pressure was (97.96±54.22) mmHg with a residual pressure of (12.95±6.42) mmHg. CONCLUSIONS: Our results show that LES was hypotensive or normotensive in the majority of the patients. Impaired relaxation was found in a minority of our patients. Aperistalsis was seen in 100% of patients. UES had impaired relaxation in a significant number of patients. Further clinical study is needed to investigate whether manometric features can predict outcomes following the studies of idiopathic achalasia.

Prevalence of cholelithiasis in patients with chagasic megaesophagus.

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18%. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p < 0.0001). The group with chagasic megaesophagus consisted of 59 (43%) women and 78 (56.9%) men, while the group with idiopathic megaesophagus consisted of 8 (53.3%) women and 7 (46.6%) men, showing no significant difference between the groups. Of the 137 patients with confirmed chagasic megaesophagus, 39 (28.4%) presented cholelithiasis versus one case (6.6%) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS: The prevalence of cholelithiasis is high in patients with chagasic megaesophagus and preoperative ultrasound should be performed routinely in these patients in order to treat both conditions during the same surgical procedure.

Prevalence of cholelithiasis in patients with chagasic megaesophagus / Prevalência de colelitíase em pacientes com megaesôfago chagásico

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18 percent. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p < 0.0001). The group with chagasic megaesophagus consisted of 59 (43 percent) women and 78 (56.9 percent) men, while the group with idiopathic megaesophagus consisted of 8 (53.3 percent) women and 7 (46.6 percent) men, showing no significant difference between the groups. Of the 137 patients with confirmed chagasic megaesophagus, 39 (28.4 percent) presented cholelithiasis versus one case (6.6 percent) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS: The prevalence of cholelithiasis is high in patients with chagasic megaesophagus and preoperative ultrasound should be performed routinely in these patients in order to treat both conditions during the same surgical procedure.

INTRODUÇÃO: A prevalência de colelitíase observada na população em geral varia de 9 a 18 por cento. Sabe-se que a prevalência de colelitíase é elevada quando existe lesão nervosa parassimpática das vias biliares, causada tanto por procedimentos cirúrgicos (vagotomias),quanto por destruição neuronal, como observado na forma digestiva da doença de Chagas. Propusemo-nos verificar a associação entre megaesôfago de etiologia chagásica e a presença de colelitíase. MÉTODOS: Avaliou-se prospectivamente o exame ultrassonográfico de 152 pacientes portadores de megaesôfago submetidos à cirurgia de cardiomiotomia e esofagectomia subtotal. Analisou-se comparativamente a esofagopatia chagásica e a idiopática com a presença de colelitíase, correlacionando os dados ultrassonográficos com os achados clínicos, idade, sexo e raça. RESULTADOS: Foram analisados 152 casos de megaesôfago, sendo 137 de etiologia chagásica e 15 idiopáticos. Entre os chagásicos, a idade média foi de 56,7 anos (45-67); e nos idiopáticos, a média de idade foi de 35,6 anos (27-44), verificando-se diferença significativa (p < 0,0001) em relação à média de idade. Dos 137 chagásicos, 78 (56,9 por cento) eram do sexo masculino; entre os 15 idiopáticos, 7 (46,6 por cento) eram do sexo masculino. A comparação entre os grupos em relação ao gênero não mostrou diferença significativa. Dentre os 137 chagásicos detectou-se 39 (28,4 por cento) casos de colelitíase e, dentre os 15 casos de megaesôfago idiopático, constatou-se colelitíase em apenas um (6,6 por cento). CONCLUSÕES: Conclui-se que portadores de megaesôfago chagásico possuem alta prevalência de colelitíase, e que a ultrassonografia deve ser realizada rotineiramente no pré-operatório, a fim de tratar ambas as afecções no mesmo ato cirúrgico.

Chagas' disease and ageing: the coexistence of other chronic diseases with Chagas' disease in elderly patients / Doença de Chagas e envelhecimento: a associação de outras enfermidades crônicas em pacientes idosos chagásicos

This study aimed to identify the main comorbidities in elderly chagasic patients treated in a reference service and identify possible associations between the clinical form of Chagas' disease and chronic diseases. Ninety patients aged 60 years-old or over were interviewed and their clinical diagnoses recorded. The study population profile was: women (55.6 percent); median age (67 years); married (51.1 percent); retired (73.3 percent); up to four years' education (64.4 percent); and earning less than two minimum wages (67.8 percent). The predominant forms of Chagas' disease were the cardiac (46.7 percent) and mixed forms (30 percent). There was a greater proportion of mild cardiac dysfunction (84.1 percent), frequently in association with megaesophagus. The mean number of concurrent diseases was 2.856 ± 1.845, and 33 percent of the patients had four or more comorbidities. The most frequent were systemic arterial hypertension (56.7 percent), osteoporosis (23.3 percent), osteoarthritis (21.2 percent) and dyslipidemia (20 percent). Positive correlations were verified between sex and comorbidities and between age group and comorbidities.

Este trabalho objetivou avaliar o perfil sociodemográfico e identificar as principais co-morbidades de idosos chagásicos, buscando associação entre forma clínica da doença de Chagas e enfermidades crônicas. Foi realizada entrevista e levantamento dos diagnósticos clínicos de 90 chagásicos com idade > 60 anos. Encontrou-se: mulheres (55,6 por cento), mediana de 67 anos, casados (51,1 por cento) e renda mensal inferior a dois salários-mínimos (67,8 por cento). A forma clínica predominante foi a cardíaca (46,7 por cento), seguida da mista (30 por cento). Houve maior proporção de cardiopatia leve (84,1 por cento), sendo frequente a associação com megaesôfago. Trinta e três por cento apresentavam quatro ou mais co-morbidades, dentre elas: hipertensão arterial (56,7 por cento), osteoporose (23,3 por cento), osteoartrite (21,2 por cento) e dislipidemia (20 por cento). Obteve-se correlação positiva entre gênero e co-morbidades, faixa etária e co-morbidades.

Preoperative gastric acid secretion and the risk to develop Barrett's esophagus after esophagectomy for chagasic achalasia.

INTRODUCTION: The aim of this study was to determine the contribution of preoperative gastric secretory and hormonal response, to the appearance of Barrett's esophagus in the esophageal stump following subtotal esophagectomy. METHODS: Thirty-eight end-stage chagasic achalasia patients submitted to esophagectomy and cervical gastric pull-up were followed prospectively for a mean of 13.6 +/- 9.2 years. Gastric acid secretion, pepsinogen, and gastrin were measured preoperatively in 14 patients who have developed Barrett's esophagus (Group I), and the results were compared to 24 patients who did not develop Barrett's esophagus (Group II). RESULTS: In the group (I), the mean basal and stimulated preoperative gastric acid secretion was significantly higher than in the group II (basal: 1.52 vs. 1.01, p = 0.04; stimulated: 20.83 vs. 12.60, p = 0.01). Basal and stimulated preoperative pepsinogen were also increased at the Group I compared to Group II (Basal = 139.3 vs. 101.7, p = 0.02; stimulated = 186.0 vs. 156.5, p = 0.07. There was no difference in preoperative gastrin between the two groups. Gastritis was present during endoscopy in 57.1% of the Group I, while it was detected in 16.6% of the Group II, p = 0.014. CONCLUSIONS: Barrett's esophagus in the esophageal stump was associated to high preoperative levels of gastric acid secretion, serum pepsinogen, and also gastritis in the transposed stomach.