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.

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.

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.

Prognostic value of natriuretic peptides in Chagas' disease: a 3-year follow-up investigation.

BACKGROUND: Chagas' disease (CD) affects around 18 million people in Latin America. To determine the diagnostic and prognostic value of natriuretic peptides in patients with CD, we measured atrial (ANP) and brain natriuretic peptide (BNP), and compared the findings with other dilated cardiomyopathies (DCM). METHODS: Blood samples were obtained from 111 CD patients, 62 patients with DCM due to other causes, and 43 gender- and age-matched healthy subjects. The CD and DCM patients were subdivided according to their NYHA classification. Natriuretic peptide concentrations were determined by immunoradiometric assays. RESULTS: ANP and more pronounced BNP levels were increased in CD and DCM patients in relation to the NYHA class. Circulating BNP concentrations were higher in CD patients in NYHA classes I-II than in the corresponding DCM patients (p = 0.020). Importantly, ANP and BNP were already significantly elevated in CD patients without systolic ventricular dysfunction (p < or = 0.001). In CD patients, both peptides were highly correlated with echocardiographic parameters (p < 10(-14)). Both ANP and BNP had comparable ability to predict death or the necessity for heart transplant (p < 0.0001). CONCLUSION: Natriuretic peptide levels can be used as a marker of asymptomatic CD without ventricular dysfunction and thus could be an ideal tool to identify these patients for early therapy.

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.

Treatment of achalasia: lessons learned with Chagas' disease.

Chagas' disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas' disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller's myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller's myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller's myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.

[Ulcerations in Chagas' megacolon operated at urgency and electively]. / Ulceras em megacólons chagásicos operados na urgência e eletivamente.

BACKGROUND: [corrected] The megacolon is a frequent disease in our emergencie hospital, and approached in the urgency by your complications as fecal impaction, volvulus and perforations. The ulcerations in the megacolons contribute as probable sites of perforations AIM: To compare the frequencies of stercoral ulceration in Chagas' megacolon operated at urgency, by volvulus or fecal impaction, and electively, aiming at a better surgical conduct in the urgency surgery METHODS: It was analyzed 356 anatomy-pathological exams from colon resection of operated patients due to Chagas' megacolon at urgency (102 cases; 29%) and electively (254 cases; 71%), from 1980 to 2000. The surgical urgency indications were attributed to volvulus (71 cases; 69,6%), fecal impaction (25 cases; 24,5%), perforated acute abdomen after rectal catheter or sigmoidoscopy (6 cases; 5,9%). The ulceration frequency was compared in both groups of resections, using chi-square RESULTS: The pathological anatomy - of surgery resection obtained at urgency surgeries, showed 26 cases of ulceration (25,5%) and in electively resections were verified 21 cases of ulceration (8,25%). The difference observed was statistically significant. The comparison among the groups of volvulus; fecal impaction and volvulus with fecal impaction, separately with electively surgery group evidenced significant differences in relation to volvulus and fecal impaction CONCLUSIONS: The higher frequency of ulcerations in the megacolon operated at urgency character emphasizes the needs of immediate resection of sigmoid colon, instead of conservative conduct of simple decompression colostomy, even in exploration laparotomy which the macroscopic examination of sigmoid does not show necrotic signs. This way, should prevent the occurrence of perforation in megacolon at mediate postoperative, with serious results.

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.

Aspects of human parasites in which surgical intervention may be important.

Until recently, physicians and surgeons in developed countries only occasionally encountered patients with parasitic protozoan and helminthic infections. High-speed travel, immigration and the popularity of the tropics as vacation areas have increased the number of people at risk for parasitic disease. This chapter examines the significant literature on a select number of protozoan and helminthic parasites for which surgical intervention is important in the diagnosis, treatment or cure of the disease. Although traditional surgical approaches are covered, emphasis is placed on recent advances in the areas of transplantation and minimally invasive surgery. Combining the disciplines of parasitology and surgery, this chapter covers three protozoan and seven helminthic parasites for which surgery is a valid treatment option based on the frequency of cases reported in the literature. Following coverage of the selected parasites, a table is included listing additional helminths for which surgery contributes to patient management. Physicians in the USA, UK, and Europe need to be more aware of the presentation and treatment of parasitic infections. It is our sincere hope that this review accomplishes that goal, and ultimately benefits the patients we serve.

Late results on the surgical treatment of Chagasic megaesophagus with the Thal-Hatafuku procedure.

BACKGROUND: Chagas' disease has a wide distribution in Central and South America. It is endemic in 21 countries, with 16 to 18 million persons infected and 100 million at risk. Surgical treatment of achalasia from Chagas' disease is the first choice in advanced stages. The aim of this study was to analyze the late clinical followup of 50 patients operated on for Chagas megaesophagus with the Thal-Harafuku procedure. STUDY DESIGN: During the period of January 1966 to January 1993, 50 patients suffering from advanced achalasia from Chagas' disease were submitted to the Thal-Hatafuku procedure. The patients answered a questionnaire concerning the most relevant postoperative symptoms. The Thal-Hatafuku procedure was performed as the first surgical option (46 patients), and on reoperations because of failure of other surgical techniques (4 patients). RESULTS: The mean followup was 63.11 months for the 44 patients with longterm followup. Postoperative complications included surgical site infection (3 of 50 patients), urinary infections (3 of 50 patients), atelectasis (2 of 50 patients), pleural effusion (2 of 50 patients), and deep venous thrombosis (1 of 50 patients). The main symptoms found in the postoperative period were dysphagia (20 of 44 patients), heartburn (11 of 44 patients), vomiting (13 of 44 patients), and retrosternal pain (6 of 44 patients). Eleven patients of the 44 remained asymptomatic at the end of the followup period. Outcomes were analyzed according to the modified Visick classification. Visick classes I and II represented 25% and 27.3%, respectively. Eighteen patients (40.9%) were classified as Visick III. CONCLUSION: We conclude that the Thal-Hatafuku operation is a therapeutic option that should be considered in the treatment of achalasia of the esophagus secondary to Chagas' disease, in advanced cases.

Postoperative complications in the treatment of chagasic megaesophagus.

The postoperative complications of Chagasic megaesophagus were studied in 250 Chagasic patients referred to the Gastroenterology Clinic of Hospital das Clinicas, Federal University of Minas Gerais, Belo Horizonte, Brazil. The treatment was balloon dilatation in 45 (18.0%), myotomy and cardioplasty in 63 (25.2%), Merendino's surgery in 139 (55.6%), esophagogastroplasty in 2 (0.8%) and esophagocoloplasty in 1 (0.4%). There were 125 (50%) early and 30 (12%) late postoperative complications, and in 65 patients (26%) recurrent dysphagia was noted: nineteen (7.6%) after myotomy and cardioplasty, 9 (3.6%) after Merendino's operation and 37 (14.8%) after balloon dilatation. Eighty-five patients (34%) needed reoperations either to correct recurrent dysphagia (56 patients, 22.4%) or to treat other complications (29 patients, 11.6%). The reoperations to correct the 19 recurrences after myotomy and cardioplasty were Merendino's operation (12 patients, 4.8%), forceful dilatation (1 patient, 0.4%), forceful dilatation followed by Merendino's (2 patients, 0.8%), another myotomy (2 patients, 0.8%), myotomy followed by Merendino and balloon dilatation (1 patient, 0.4%) or esophagogastroplasty (1 patient, 0.4%). The recurrences after dilatation were treated by myotomy (15 cases, 6%), Merendino's operation (12 cases, 4.8%) and myotomy followed by Merendino's (3 cases, 1.2%). After Merendino seven reoperations (2.8%) were done: reduction of interposed loop (6 cases, 2.4%) and esophagocoloplasty (1 case, 0.4%). The time elapsed between the first operation and reoperation or dilatation varied from a few weeks to 18 years.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the quality of life in patients with Chagas' disease undergoing a heart transplant]. / Avaliação da qualidade de vida de pacientes com doença de Changas submetidos a transplante de coração.

Quality of life was evaluated in 11 patients with Chagas' disease 26 to 126 months after submission to heart transplantation. There was an objective improvement in their quality of life, after the transplant.

[Surgical treatment of megaesophagus. Effect of myotomy and fundoplication on the lower esophageal sphincter]. / Tratamento cirúrgico do megaesôfago. Efeito da miotomia e da valvuloplastia sobre o esfíncter inferior do esôfago.

Details about the structure of the lower esophageal sphincter and the function of fundoplication are yet unknown. New study is presented about electromanometric examination of the lower esophageal sphincter in 20 chagasic patients with megaesophagus operated on by cardiomyotomy complemented with His angle agudization (Group A-10 patients) or fundoplication (Group B-10 patients). On the 30th postoperative day, the patients, without dysphagia, were submitted to radiologic study, demonstrating valvuloplasty integrity (Group B), and electromanometric study of the esophagus. The comparison between the groups demonstrated: -myotomy does not modify the lower esophageal sphincter extension, but decrease its pressure, not to zero; -fundoplication does not increase the lower esophageal sphincter pressure after myotomy, under resting conditions. These conclusions suggest that: -lower esophageal sphincter is formed by muscular fibers interlacing, configuration that maintains residual regional pressure after myotomy; - in resting state, after myotomy, fundoplication exerts exclusively mechanical function, without increase of the lower esophageal sphincter pressure.

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.