Epithelial cell types and their proposed roles in maintaining the mucosal barrier in human chagasic-megacolonic mucosa.

Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive this chronic disease for decades. A key structure of the mucosal barrier are epithelial cells. Vasoactive-intestinal-peptide (VIP)-positive nerve fibres are involved in influencing, e.g., epithelial cell proliferation, mucus secretion (e.g., mucin 2 and trefoil factor 3 of goblet cells) and inflammation or autoimmunity, all putative and/or known factors altered in chagasic megacolon. We analyzed qualitatively and quantitatively goblet cells, their specific markers, such as mucin 2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the relation of VIP-immunoreactive nerve fibres to the epithelia, the distribution of gelsolin, a protein involved in chronic inflammation processes in the epithelia, and the proliferation rate of epithelial cells by combined 4',6-diamidino-2-phenylindole (DAPI) and phosphohistone-H3 (PHH3) staining. Goblet cells were the dominating epithelial cell type. They accounted for 38.4% of all epithelial cells in controls and changed to 58.9% in the megacolonic parts. In contrast to the overall expression in goblet cells of control epithelia, TFF3 was confined to goblet cells at the base of the crypts whereas MUC2 was found only in luminal goblet cells. Gelsolin-positive goblet cells were predominantly recognized within the controls. Finally, the mean value of mitosis increased from 1.5% within the controls up to 2.6% in the anal parts of the chagasic sepcimens. Taken together, increased cell proliferation, preponderance of goblet cells, differential MUC 2, and TFF 3 expression might all be factors maintaining an intact mucosal barrier within chagasic megacolon.

Early and late assessment of esophagocardioplasty in the surgical treatment of advanced recurrent megaesophagus / Avaliação precoce e tardia da esofagocardioplastia no tratamento cirúrgico do megaesôfago avançado e recidivado

ABSTRACT Background Since Chagas disease has esophageal manifestations with different degrees of involvement, the best surgical option is controversial, especially for patients with advanced chagasic megaesophagus and recurrent symptoms after previous treatment. Objective To assess the early and late outcomes of esophagocardioplasty in a series of patients with advanced recurrent chagasic megaesophagus. Methods This descriptive study included 19 older patients with recurrent megaesophagus grade III/IV and positive immunofluorescence for Chagas disease. They had undergone cardiomyotomy with anterior fundoplication a mean of 16.5 years ago. Serra-Doria esophagocardioplasty was selected to treat the recurrence. The patients were followed to assess postoperative and late complications and the incidence of symptom recurrence. Results In early assessment, five (26.3%) patients presented clinical complications. One (5.2%) patient had a gastrointestinal fistula secondary to esophagogastric anastomotic leak, which responded well to conservative treatment. In the one-year follow-up, 18 (94.7%) patients could swallow normally and had no vomiting. Three years after surgery, 10 (62.5%) of 16 patients could swallow normally, and 3 (19.3%) patients complained of vomiting. Five years after surgery, only 5 (38.4%) of 13 patients could swallow normally and 7 (53.8%) had vomiting. Conclusion Serra-Doria esophagocardioplasty for the treatment of advanced recurrent megaesophagus had mild postoperative complications and good success rate in the short-term follow-up. In the long-term follow-up, it proved to be a poor surgery choice because of the high incidence of symptom recurrence, compromising quality of life. This procedure should be indicated only for patients with advanced recurrent megaesophagus without clinical conditions to undergo esophageal resection.

RESUMO Contexto A doença de Chagas, por apresentar manifestações esofágicas com diferentes graus de acometimento, faz com que haja controvérsias quanto a melhor opção cirúrgica; principalmente para pacientes com megaesôfago chagásico avançado e com recidiva de sintomas após tratamento prévio. Objetivo Avaliar o resultado precoce e tardio da esofagocardioplastia em uma série de pacientes com megaesôfago chagásico avançado e recidivado. Métodos Estudo descritivo, com 19 pacientes idosos com megaesôfago Grau III/IV recidivado e com imunoflorescência positiva para doença de Chagas. A cirurgia prévia foi a cardiomiotomia com fundoplicatura anterior, com tempo médio de realização de 16,5 anos. A cirurgia de eleição para o tratamento da recidiva foi a esofagocardioplastia de Serra-Dória. Realizou-se avaliação precoce para estudar as complicações pós-operatórias e tardias, para avaliar a incidência de recidiva de sintomas. Resultados Na avaliação precoce, 5 (26,3%) pacientes apresentaram complicações clínicas. Um (5,2%) paciente apresentou fístula digestiva consequente a deiscência da anastomose esofagogástrica, mas com boa evolução com o tratamento conservador. Na avaliação de 1 ano de pós-operatório, 18 (94,7%) pacientes apresentavam deglutição normal e sem regurgitação. Com 3 anos de pós-operatório, de 16 pacientes analisados; 10 (62,5%) pacientes apresentavam deglutição normal e 3 (19,3%) se queixavam de regurgitação. Com 5 anos de pós-operatório, de 13 pacientes analisados; somente 5 (38,4%) apresentavam deglutição normal e 7 (53.8%) com regurgitação. Conclusão A esofagocardioplastia de Serra-Dória, no tratamento cirúrgico do megaesôfago avançado recidivado, apresentou complicações pós-operatórias de baixa morbidade e com boa resolutividade, na avaliação precoce. Na avaliação de longo prazo, demonstrou não ser um procedimento cirúrgico adequado, pela alta incidência de recidiva de sintomas, com comprometimento da qualidade de vida. Deve ser indicada somente em pacientes com doença avançada recidivada, sem condições clínicas de serem submetidas à ressecção esofágica.

EARLY AND LATE ASSESSMENT OF ESOPHAGOCARDIOPLASTY IN THE SURGICAL TREATMENT OF ADVANCED RECURRENT MEGAESOPHAGUS.

BACKGROUND: Since Chagas disease has esophageal manifestations with different degrees of involvement, the best surgical option is controversial, especially for patients with advanced chagasic megaesophagus and recurrent symptoms after previous treatment. OBJECTIVE: To assess the early and late outcomes of esophagocardioplasty in a series of patients with advanced recurrent chagasic megaesophagus. METHODS: This descriptive study included 19 older patients with recurrent megaesophagus grade III/IV and positive immunofluorescence for Chagas disease. They had undergone cardiomyotomy with anterior fundoplication a mean of 16.5 years ago. Serra-Doria esophagocardioplasty was selected to treat the recurrence. The patients were followed to assess postoperative and late complications and the incidence of symptom recurrence. RESULTS: In early assessment, five (26.3%) patients presented clinical complications. One (5.2%) patient had a gastrointestinal fistula secondary to esophagogastric anastomotic leak, which responded well to conservative treatment. In the one-year follow-up, 18 (94.7%) patients could swallow normally and had no vomiting. Three years after surgery, 10 (62.5%) of 16 patients could swallow normally, and 3 (19.3%) patients complained of vomiting. Five years after surgery, only 5 (38.4%) of 13 patients could swallow normally and 7 (53.8%) had vomiting. CONCLUSION: Serra-Doria esophagocardioplasty for the treatment of advanced recurrent megaesophagus had mild postoperative complications and good success rate in the short-term follow-up. In the long-term follow-up, it proved to be a poor surgery choice because of the high incidence of symptom recurrence, compromising quality of life. This procedure should be indicated only for patients with advanced recurrent megaesophagus without clinical conditions to undergo esophageal resection.

Acute colonic complications in a patient with Chagas disease.

We present the case of a young bolivian woman who suffered two acute and impressive colonic complications due to a Chagasic megacolon.

Is it safe to use a liver graft from a Chagas disease-seropositive donor in a human immunodeficiency virus-positive recipient? A case report addressing a novel challenge in liver transplantation.

This is the first report presenting a human immunodeficiency virus (HIV)-positive patient with fulminant hepatic failure receiving a liver graft from a Chagas disease-seropositive deceased donor. We describe the history of a 38-year-old HIV-positive female patient who developed fulminant hepatic failure of an autoimmune etiology with rapid deterioration of her clinical status and secondary multiorgan failure and, therefore, needed emergency liver transplantation (LT) as a lifesaving procedure. Because of the scarcity of organs and the high mortality rate for emergency status patients on the LT waiting list, we decided to accept a Chagas disease-seropositive deceased donor liver graft for this immunocompromised Chagas disease-seronegative patient. The recipient had a rapid postoperative recovery and was discharged on postoperative day 9 without prophylactic treatment for Chagas disease. Fifteen months after LT, she was still alive and had never experienced seroconversion on periodic screening tests for Chagas detection. Although there is an inherent risk of acute Chagas disease developing in seronegative recipients, our report suggests that these infected organs can be safely used as a lifesaving strategy for HIV patients with a high need for LT.

Radiofrequency ablation of a left accessory pathway unmasks classic Chagas' disease ECG pattern.

In patients with chronic Chagas' cardiomyopathy, there are forms of the disease that affect the electrical conduction system almost exclusively. The most common disorders include right bundle branch block alone or in association with left anterior fascicular block. We present an unusual case of a patient with Chagas' cardiomyopathy in association with a preexcitation syndrome.

Reduced population of interstitial cells of Cajal in Chagasic megacolon.

BACKGROUND/AIMS: In Chagasic megacolon, there is a reduction in the population of interstitial cells of Cajal. It was aimed to evaluate density of Cajal cells in the resected colon of Chagasic patients compared to control patients and to verify possible association between preoperative and postoperative bowel function of megacolon patients and cell count. METHODOLOGY: Sixteen megacolon patients (12 female; mean age 54.4 (31-73)) were operated on. Pre- and postoperative evaluation using Cleveland clinic constipation score was undertaken. Resected colons were examined. Cajal cells were identified by immunohistochemistry (anti-CD117). The mean cell number was compared to resected colons from 16 patients (7 female; mean age 62.8 (23-84)) with non-obstructive sigmoid cancer. Association between pre- and postoperative constipation scores and cell count for megacolon patients was evaluated using the Pearson test (r). RESULTS: A reduced number of Cajal cells (per field: 2.84 (0-6.6) vs. 9.68 (4.3-13); p<0.001) were observed in the bowel of megacolon patients compared to cancer patients. No correlation between constipation score before (r=- 0.205; p=0.45) or after surgery (r=0.291; p=0.28) and cell count in megacolon was observed. CONCLUSIONS: Patients with megacolon display marked reduction of interstitial cells of Cajal. An association of constipation severity and Cajal cells depopulation was not demonstrated.

Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas.

The substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of organs and tissues. In addition, an increasing number of patients with advanced Chagas heart disease may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease. Therefore, it is necessary to establish protocols for disease management. This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease and summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues, or hematopoietic stem cells and aims to help professionals working in this field. A single registry of transplants in Trypanosoma cruzi infected donors and/or recipients will provide and disseminate experience in this area, which has shown a low recorded incidence to date.

Usefulness of qualitative polymerase chain reaction for Trypanosoma cruzi DNA in endomyocardial biopsy specimens of chagasic heart transplant patients.

BACKGROUND: Chagas' disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. CDR affecting the myocardium induces lymphocytic myocarditis and should be distinguished from acute cellular rejection in endomyocardial biopsy (EMB) specimens. METHODS: We performed retrospectively qualitative polymerase chain reaction for T cruzi DNA using 2 sets of primers targeting nuclear DNA (nDNA) or kinetoplast DNA (kDNA) in 61 EMB specimens of 11 chagasic heart transplant recipients who presented with CDR. Thirty-five EMB specimens were obtained up to 6 months before (pre-CDR group) and 26 up to 2 years after the diagnosis of CDR. The control group consisted of 6 chagasic heart transplant recipients with 18 EMB specimens who never experienced CDR. RESULTS: Amplification of kDNA occurred in 8 of 35 (22.9%) EMB specimens of the pre-CDR group, in 5 of 18 (27.8%) of the control group, and in 17 of 26 (65.4%) EMB specimens obtained after the successful treatment of CDR. Amplification of nDNA occurred in 3 of 35 (8.6%) EMB specimens of the pre-CDR group, 0 of 18 (0%) of the control group, and 6 of 26 (23.1%) EMB specimens obtained after the successful treatment of CDR. CONCLUSIONS: Amplification of kDNA in EMB specimens is not specific for the diagnosis of CDR, occurring also in patients with no evidence of CDR (control group). However, amplification of nDNA occurred in a few EMB specimens obtained before CDR, but in none of the control group specimens. Qualitative PCR for T cruzi DNA in EMB specimens should not be used as a criterion for cure of CDR because it can persist positive despite favorable clinical evolution of the patients.

Heart transplantation in 107 cases of Chagas' disease.

INTRODUCTION: Chagas' disease is endemic in South America. OBJECTIVE: This research reviewed the experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas' disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. RESULTS: The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n = 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas' disease in the central nervous system (n = 1; 7.1%). CONCLUSIONS: Transplantation in Chagas' disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.

Chagas' disease and solid organ transplantation.

This review summarizes relevant published data on transplant recipients with Chagas' disease and of naïve recipients transplanted with organs from infected donors. Unpublished experience from some of the largest transplant centers in Argentina is also included. The review outlines the guidelines for pretransplant evaluation and for posttransplant management formulated by the Chagas Disease Argentine Collaborative Transplant Consortium.

Sustitución valvular en un paciente con enfermedad de Chagas. Consideraciones anestésicas / No disponible

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A systematic review of studies on heart transplantation for patients with end-stage Chagas' heart disease.

BACKGROUND: Uncertainties regarding indications for the procedure, proper immunosuppressive regimen, and the fear of Trypanosoma cruzi infection reactivation are major concerns regarding heart transplantation (HTx) for patients with end-stage Chagas' heart disease. METHODS AND RESULTS: To review indications for HTx, current immunosuppressive therapy, posttransplant morbidities, and outcome in Chagas' heart transplant recipients. Review of articles linking HTx and Chagas' disease at PubMed and Scielo database from 1966 onward. HTx can reasonably be indicated in patients with an annual probability of death of 70%. HTx has been associated with a similar incidence of rejection episodes in Chagas' and non-Chagas' heart transplant recipients. A lower incidence of infection episodes has been observed in Chagas' in comparison to non-Chagas' heart transplant recipients. T. cruzi infection reactivation is easily treated with either benznidazole or allopurinol and portends a very low mortality rate. Other posttransplant morbidities have a similar incidence in Chagas' and in non-Chagas' patients. Survival probability for Chagas' HTx recipients at 1 month, 1 year, 4 years, and 10 years follow-up is 83%, 71%, 57%, and 46%, respectively. Such an outcome is better than that seen in non-Chagas' heart transplant recipients. CONCLUSIONS: HTx is safe and efficacious for patients with end-stage Chagas' heart disease.

Surgical treatment of Chagas megacolon. Critical analysis of outcome in operative methods.

PURPOSE: Surgical treatment of chagasic megacolon has suffered innumerable transformations over the years. Poor knowledge of the disease physiopathology is one of the reasons. METHODS: From January 1977 to December 2003, 430 patients were submitted to surgical treatment for chagasic megacolon. Of these procedures, 351 were elective and 79 emergency operations carried out at the University Hospital of Ribeirão Preto. Four elective operations, most frequently used, should be singled out: anterior rectosigmoidectomy (52.71%), left hemicolectomy (18.23%), Duhamel-Haddad operation(15.95%), and total colectomy (5.98%). From the 79 exploratory laparotomies performed on an emergency basis, 53 (67.09%) required intestinal resection. From the 430 patients operated upon, 268 (62.33%) progressed without recurrence of intestinal constipation, and 71 (15.51%) had a recurrence. RESULTS AND DISCUSSION: Based on the data collected, left hemicolectomy had the highest constipation recurrence rate compared to other operating procedures; anterior retosigmoidectomy had less complication episodes and a larger recurrence of intestinal constipation in comparison to the Duhamel-Haddad operation. Emergency operations, mainly for the treatment of volvulus and fecaloma, presented high morbidity and mortality and required extensive intestinal resections, stomas and reoperations.

Trypanosoma cruzi: orchiectomy and dehydroepiandrosterone therapy in infected rats.

The ability of gonadal hormones to influence and induce diverse immunological functions during the course of a number of parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulfate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. The effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA were examined, by comparing blood and cardiac parasitism, macrophage numbers, nitric oxide and IFN-gamma levels. Orchiectomy enhanced resistance against infection with elevated numbers of macrophages, enhanced concentrations of NO and IFN-gamma and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergistic effect, up-modulating the immune response. Male sex steroids appear to play fundamental role in determining the outcome of disease, through the regulation and modulation of the activity of the immune response.