Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

Chaga's disease is an important communicable neglected disease that is gaining wider attention due to its increasing incidence worldwide. Achalasia due to chagasic megaesophagus (CM), a complication of this disease, is a known-yet, poorly understood-etiological factor for esophageal squamous cell carcinoma (ESCC) development. In this study, we aimed to perform the analysis of TP53 mutations in a series of Brazilian patients with ESCC that developed in the context CM (ESCC/CM), and to compare with the TP53 mutation profile of patients with benign CM and patients with nonchagasic ESCC. Additionally, we intended to correlate the TP53 mutation results with patient's clinical pathological features. By polymerase chain reaction (PCR) followed by direct sequencing of the hotspot regions of TP53 (exon 5 to 8), we found that TP53 mutations were present in 40.6% (13/32) of the ESCC/CM group, 45% (18/40) of the nonchagasic ESCC group, and in only 3% (1/33) of the benign CM group. Missense mutations were the most common in the three groups, yet, the type and mutated exon mutation varied significantly among the groups. Clinically, the groups exhibited distinct features, with both cancer groups (ESCC and ESCC/CM) been significantly associated higher consumption of alcohol and tobacco, older age, worse Karnofsky performance status, poor outcome than the patients with benign CM. No significant association was found between TP53 mutation profile and clinical-pathological features in any of the three groups. We describe first the time the analysis of TP53 mutations in ESCC that developed in the context of CM, and the observed high frequency of mutations, suggest that TP53 also plays an important role in the tumorigenic process of this unexplored etiological condition.

Giant placental chorioangioma with favorable outcome: a case report and literature review of literature.

OBJECTIVE: To describe a case of prenatal diagnosis of a giant placental chorioangioma with favorable outcome. DESIGN: A case report. SETTING: Gynecology and Obstetrics Service, Federal University of Triângulo Mineiro (UFTM), Uberaba-MG, Brazil. CASE REPORT: The placental chorioangioma is the most common benign tumor, but the type giant has a small prevalence, ranging from 1:16.000 to 1:50.000 pregnancies. We reported a case of a patient aged 18, pregnant for the first time, who performed a routine obstetric ultrasound was found to have polyhydramnios associated with placental vascular lesions suggestive of chorioangioma also was defined by fetal magnetic resonance imaging and confirmed by pathological examination.

GTPases Rho distribution in intraepithelial and invasive neoplasias of the uterine cervix.

PURPOSE OF INVESTIGATION: To evaluate the distribution of GTPases RhoA, RhoB, and Cdc42 in cervical intraepithelial neoplasias (CIN) and invasive neoplasias of the uterine cervix. MATERIALS AND METHODS: samples of neoplastic lesions of the uterine cervix of 44 patients were classified in: CIN I (n = 10), CIN II (n = 10), CIN III (n = 09), and invasive carcinoma (n = 15). Antibodies anti-RhoA, anti-RhoB, and anti-Cdc42 were used and staining was classified as: negative, mild, moderate, and intense positive. RESULTS: When compared with dysplastic cells, superficial cells showed: higher expression of RhoB in CIN I (p = 0.0018), and lower expression of Cdc42 in CIN I (p = 0.0225). The authors observed higher expression of RhoA (p = 0.0002) and RhoB (p = 0.0046) in CIN dysplastic cells when compared with invasive carcinoma cells. CONCLUSIONS: GTPases Rho may be involved with the regulation of biological processes, important to the progression of cervical neoplasias. Probably, RhoA is important for maintenance of cell differentiation and RhoB protects cells from malignant cervical neoplasia.

Frequency of endometriosis and adenomyosis in patients with leiomyomas, gynecologic premalignant, and malignant neoplasias.

OBJECTIVE: This study investigated the association between gynecological neoplasms, endometriosis, and adenomyosis in women who underwent surgical treatment for gynecological cancer and uterine leiomyoma during reproductive years or after menopause. MATERIALS AND METHODS: Information was collected from patient records from the Hospital's database from 1985 to 2007. The study included 502 women, of which 375 were premenopausal and 132 were postmenopausal. RESULTS: A significant association was observed between the occurrence of adenomyosis in cancer in women with four or more pregnancies, and in women aged over 40 years (p < 0.0001). The frequency of adenomyosis was significantly higher than the frequency of endometriosis for cancer in two sites (p = 0.0419) or for leiomyomas (p < 0.0001). CONCLUSION: Therefore adenomyosis is more frequently found than endometriosis in women with leiomyomas or cancer in two sites in premenopausal women, and clinicians need to be aware of patients with adenomyosis and the risk of cancer.

Frequency of recurrence after surgical treatment of cervical intraepithelial neoplasia grade 1-3.

PURPOSE OF INVESTIGATION: The objective was to demonstrate the frequency of invasive cervical cancer or recurrent CIN in patients treated by a previous diagnosis of CIN 1-3. METHODS: We analyzed 1,397 records colpocytologic and medical records. Recurrence of CIN or invasive neoplasia of the cervix after treatment of CIN was assessed. The chi-square test was used for statistical analysis (significance level set at less than 0.05). RESULTS: We obtained 696 CIN 1, 244 CIN 2, 451 CIN 3, and six squamous carcinoma. Regarding patients who relapsed, there were 6/690 (0.9%) patients had an initial diagnosis of CIN 1, 8/236 (3.4%) CIN 2 and 21/430 (4.9%) CIN 3 (p < 0.0001). Comparing the frequency of relapse among each group, we found: CIN 1 vs CIN 2: p = 0.0073; CIN 1 vs CIN 3: p < 0.0001; CIN 2 vs CIN 3: p = 0.38. CONCLUSION: Although the number of relapses when comparing CIN 2 and CIN 3 were not significant, the data suggest that CIN 2 has lower recurrence rates, so these patients require more conservative treatment if a desire of future pregnancy is expressed.

Immunological evaluation of vaginal secretion in patients with high-grade cervical intraepithelial neoplasia treated with intralesional interferon alpha-2b.

INTRODUCTION: Conservative treatment with intralesional interferon (IFN) is a therapeutic option for cervical intraepithelial neoplasia (CIN) patients of childbearing age. MATERIALS AND METHODS: The study group was made up of patients diagnosed with a high-grade lesion and treated with intralesional human recombinant IFNalpha-2b. Vaginal secretion was collected during IFNalpha-2b treatment for analysis of cytokines and viral load. RESULTS: The initial histology diagnostic was 62.5% (n = 5) with CIN 2 and 37.5% (n = 3) with CIN 3. In terms of clinical evaluation and anatomopathology, 6.5% (n = 5) had a good clinical response, while 37.5% (n = 3) had therapeutic failure. All the patients with therapeutic failure were smokers. Interleukin 6 and tumor necrosis factor-alpha concentrations were raised at the sixth application for the patient group who failed to respond to therapy compared to the responsive group (p = 0.0357). Patients with a good response exhibited a reduction in human papillomavirus viral load (p = 0.03). CONCLUSIONS: Patients that had a good response had lower concentrations of inflammatory cytokines than did non-responders.

Expression of cytokines in cervical stroma in patients with high-grade cervical intraepithelial neoplasia after treatment with intralesional interferon alpha-2b.

Conservative treatment with interferons (IFNs) has the advantage of preserving reproductive capacity in patients with grade 2 or 3 cervical intraepithelial neoplasia (CIN). The objective of this work was to study patients with high-grade CIN treated with intralesional IFN alpha-2b and to analyze the expression of Th1, Th2 and Th3 cytokines in cervical stroma. We observed that patients with a satisfactory response (60%) to treatment with IFN alpha-2b expressed more Th1 (IFN-gamma TNF-alpha, IL-2) cytokines, with a significant reduction in the viral load of high-risk human papillomavirus (p = 0.0313). All patients with therapeutic failure were smokers and had higher expression of cytokines Th2 (IL-4) or Th3 (TGF-beta2 and TGF-beta3).

T lymphocytes (CD3) may participate in the recurrence of cervical intraepithelial neoplasia grade III.

OBJECTIVE: Data from the literature demonstrate that the local and systemic immune responses seem to play an important role in the progression of cervical intraepithelial neoplasia (CIN). Our aim was to investigate whether recurrences among CIN III patients might be related to the presence of local lymphocytes, macrophage and enzyme iNOS. METHODS: We analyzed 35 patients with CIN III who underwent conization and followed up for a minimum of 4 years. Using immunohistochemistry, the presence of T lymphocytes (CD3, CD8 and CD45RO), B lymphocytes (CD20), macrophages (CD68) and the expression of the enzyme iNOS were investigated. The quantity of marked cells is graded as: 0, absence of cells; 1, rare cells; 2, moderate number of cells; 3, many cells. For statistical purposes, we took the scores 0 and 1 to indicate weak marking and the scores 2 and 3 to indicate strong marking. RESULTS: We found strong positive expression of CD3-positive T lymphocytes among CIN III patients with recurrence following conization (100 vs. 50% without recurrence, p=0.02). We did not find any statistical differences in the expression of CD20, CD68, CD45RO, CD8 or iNOS. CONCLUSIONS: It is concluded that strong positive findings of CD3 T lymphocytes were related to recurrence following conization due to CIN III.

Androgenic juvenile granulosa cell tumor of the ovary with cystic presentation: a case report.

Granulosa cell tumors account for approximately 1-2% of all ovarian tumors. There are two types: adult granulosa cell tumor and juvenile granulosa cell tumor. Juvenile granulosa cell tumors constitute 5% of this histological subtype, and the prognosis is good because the majority present as Stage I tumors. The treatment can consist of conservative surgery. Androgen production is rare and produces virilization in women. These tumors are usually solid or predominantly solid. We describe the case of a 13-year-old girl with androgenic manifestations and increased abdominal size. Her plasma testosterone level was elevated. A left adnexal cyst (14.4 x 9.1 x 9.7 cm) was revealed at pelvic ultrasonography. The patient underwent an exploratory laparotomy, revealing a left ovarian cystic tumor. Diagnosis was juvenile granulosa cell tumor.

Cervical neoplasia after diagnosis and follow-up of women with atypical squamous cells of undetermined significance.

BACKGROUND: Although the cytological finding of atypical squamous cells of undetermined significance (ASCUS) occurs in around 5% of women undergoing cytological screening, the clinical evolution is unknown. The objective of this study was to evaluate women with a diagnosis of ASCUS and compare the histological findings and clinical evolution over six and 12 months. METHODS: 1244 patients with ASCUS (two diagnostic cytologists) were evaluated in this study with Pap Smears and colposcopy (biopsy if necessary) at the first visit, and thereafter at second and third visits (6 and 12 months after the first visit). Comparisons were made between cytological findings and histological diagnoses at every visit during the study and during evolution. RESULTS: At the first visit, 60.3% of the biopsied patients presented histological findings of CIN I, 17.46% CIN II/III and 6.3% invasive neoplasia. At the second visit, 48.3% of the biopsied patients presented CIN I, 24.1% CIN II/III and none invasive neoplasia. At the third visit, 68.9% of the biopsied patients presented CIN I, 13.8% CIN II/III and none invasive carcinoma. If we consider all visits, a total of 213 colposcopy-guided biopsies were performed, representing 17.1% of all the patients included. Of these, 164 (13.2%) presented a histological diagnosis of cervical intraepithelial neoplasia (CIN) and eight (0.6%) presented with invasive carcinoma. CONCLUSION: We conclude that CIN or invasive lesions frequently occur in women with a diagnosis of ASCUS. Immediate review of the thin sections, new cytological tests or colposcopy and rigorous follow-up should be considered when making a diagnosis of ASCUS.

Choriocarcinoma complicated by a vaginal fistula, sepsis and hemorrhagic shock. Case report.

A case of poor prognostic choriocarcinoma developing sepsis is described. The patient was treated with vaginal drainage of pelvic abscess metastases, bilateral hypogastric artery ligation to prevent hemorrhage and single-agent chemotherapy.

Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis.

This study was made with the objective of reevaluating the colon denervation in chronic Chagas' disease. The diameters of neuron perikaryons of the myenteric plexus were measured on paraffin sections in a ring from the sigmoid in Chagas' disease patients, 17 with and 10 without megacolon and in 10 non-chagasic controls. All neurons were counted in ten en-echelon sections. Neuron hypertrophy only occurred in the group with megacolon, and the average increase in diameter was 69.3%. This could generate an error factor in the neuron count by increasing the probability of neurons being seen in a greater number of histological sections. The original result of the neuron count gave medians of 1264, 1961, and 2665 in the groups of chagasic patients with megacolon, without megacolon, and in the control, respectively. The denervation was greater than 55% in only seven megacolon cases (41.2%). After applying a correction factor, the median in the group with megacolon was 746, and the denervation was greater than 55% in 13 cases (76.5%). This occurrence demonstrates the need to apply a correction factor when the neuron count in chagasic megacolon is being evaluated and in the other pathologies where neuron hypertrophy may be found.

Leiomyosarcoma of the esophagus in a patient with chagasic megaesophagus: case report and literature review.

Leiomyosarcoma constitutes approximately 0.5% of the malignant neoplasias of the esophagus and its association with megaesophagus has not been described. We report on a case of a woman with dysphagia that was slowly progressive from the age of 19 due to chagasic megaesophagus. The woman was subjected to cardiomyotomy at the age of 49. She presented a rapid worsening of the dysphagia due to leiomyosarcoma at the age of 61, and was subjected to subtotal esophagectomy with cervical esophagogastroplasty. She developed pulmonary and hepatic metastases 14 months after surgery and died six months later.

A study of experimental reinfection by Trypanosoma cruzi in dogs.

The role of reinfection in the evolution of Chagas' disease was evaluated in dogs alternately infected with the 147 and SC-1 strains of Trypanosoma cruzi. A parasitologic, serologic, clinical, and electrocardiographic follow-up was carried out on the infected and noninfected dogs. The dogs were reinfected five times over a period of 38 months. No deaths were observed during the experiment. They presented a brief oligosymptomatic acute phase. The level of parasitemia decreased progressively with the number of reinfections. Bloodstream parasites were not detectable after the fifth reinfection. All parasite samples isolated during the follow-up were zymodeme B, corresponding to strain 147, irrespective of the strain with which the dogs were first infected and of the triatomine species used for isolation. Conversely, amplification by the polymerase chain reaction of a segment of the T. cruzi mini-exon gene showed the simultaneous presence of both strains in three of the eight reinfected animals. Antibody titers were greater among the dogs successively infected than those infected only once. Neither amastigotes nor T. cruzi DNA were detected in the tissues of the infected dogs. Alterations related to Chagas' disease were identified only in the heart and consisted of chronic focal and discrete myocarditis, compatible with the indeterminate form of Chagas' disease. All infected dogs developed this form of the disease, which was independent of the number of infections.

Low-grade cervical squamous intraepithelial lesion during pregnancy: conservative antepartum management.

The purpose of this retrospective study was to determine the regression rate and management of low-grade squamous intraepithelial lesions (LSIL) in pregnancy. Seventy-four women with cytological findings of LSIL were analysed during the pregnant-puerperal period (until 12 months postpartum). Age, parity, cytological and colposcopic findings, route of delivery, and postpartum follow-up were studied. The age and parity of patients ranged (average) from 12 to 32 years (21.2 +/- 4.9), 0-5 (0.89 +/- 1.14), and 9-32 years (16.1 +/- 3.5), respectively. Thirty-nine of 55 (70.9%) and 12 of 19 (63.1%) pregnant women had normal cytology after vaginal delivery and caesarean section, respectively (p > 0.05). In postpartum, eight patients (10.8%) persisted with LSIL and ten (13.5%) presented high-grade squamous intraepithelial lesions. No case of unsatisfactory colposcopy and invasive carcinoma were found. LSIL during pregnancy has a high rate of regression, regardless of the route of delivery. Conservative management with colposcopic evaluation is proposed during gestation.

Outcome after treatment of high-grade squamous intraepithelial lesions: relation between colposcopically directed biopsy, conization and cervical loop excision.

PURPOSE OF INVESTIGATION: The hypothesis that cold-knife conization performed in women with high-grade squamous intraepithelial lesions (HSIL) and unsatisfactory colposcopy is a better procedure than the loop electrosurgical procedure (LEEP) is tested. METHODS: A retrospective study was conducted in conization specimens of women submitted to LEEP (n = 102) or conization (n = 245) due to HSIL. Age, biopsy, compromised surgical margins in conization, and recurrence were analysed. RESULTS: The frequency of invasion, non-compromised margins, and recurrence in conization and LEEP were, respectively, 7.7% versus 2.9%, 64.1% versus 48% (p = 0.008), and 33.8% versus 24.1%. Eight (42.1%) and five (26.3%) of 19 women submitted to conization where invasion was found in surgical specimens were, respectively, menopausal or had unsatisfactory colposcopy. Twenty-five (96.2%) of 26 and 23 (95.8%) of 24, respectively, undergoing conization and LEEP had recurrence in the first five years. CONCLUSION: We recommend the use of cold-knife conization in cases where the lesion is located deep in the cervical canal.

[Pathological anatomy of chagasic megaesophagus]. / Contribuição ao estudo da anatomia patológica do megaesôfago chagásico.

Systematized study was made in 56 esophagi of chronic chagasics (17 with and 39 without megas) aiming to: 1) to evaluate the esophageal caliber and thickness ranges; 2) analyse qualitative and quantitatively, the myenteric plexuses, trying to evaluate the relation of their lesions and the development of megaesophagus (ME); 3) study the lesions of the muscularis propria to verify if they contribute or not to the beginning of the process; 4) search for T. cruzi and its eventual relationship with the inflammation; 5) identify the principal mucosal alterations. It was confirmed that the severest lesions were found in the muscularis propria and in the plexures of Auerbach ganglia. In the former, the main alterations were myositis and fibrosis. The myentric plexuses showed inflammation and neuronal depopulation when compared with non-mega chagasic esophagi and even more when compared with the controls. On the other hand, there were normal caliber esophagi with severe denervation. It is possible that several factors may lead to the esophagopathy, especially to the ME. The search for T. cruzi was found positive in four out of eight esophagi with mega and in none of eight chagasic esophagi without mega. Mucosal and submucosal lesions were unremarkable and do not seem to be involved with the development of the process.

[Residual histoplasmosis of the lung and bronchopulmonary lymph nodes in autopsies carried out in Uberaba, MG]. / Histoplasmose residual dos pulmões e linfonodos broncopulmonares em necropsias realizadas em uberaba, MG.

Lungs and broncho-pulmonary lymph nodes were studied from 127 sequential adult autopsies done in Uberaba, MG, Brazil through the years 1992 and 1993. Calcified lung nodules and/or calcified lymph nodes were found in 39 (30.7%) cases. For 27 (69.2%) out of those 39 autopsies, fungi morphologically compatible with Histoplasma capsulatum were found within those calcified structures. Fite-Faraco stain for acid-fast bacilli was negative for all cases. It is concluded that the majority of calcified pulmonary nodes and calcified regional lymph nodes found at autopsies in Uberaba are related to infection with H. capsulatum. These findings raise the possibility for this fungal disease to be endemic in Uberaba. Such information might be relevant to the diagnosis of this systemic mycosis.

Pulmonary adiaspiromycosis: report of two cases.

Two cases of human pulmonary adiaspiromycosis are reported. Patients were 29 and 54-year-old males, farm workers, with "grippe-like" symptoms and radiographic findings suggestive of granulomatous interstitial disease. Transthoracoscopic and transbronchial biopsies were performed. Pulmonary function was measured by spirometry. One patient used ketoconazole. Possibility of misdiagnosed pulmonary adiaspiromycosis is emphasized.