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Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC)., Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals., Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology., Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics., Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM., (© 2021 S. Karger AG, Basel.)

Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.

Bronchoalveolar lavage, bronchial brushing and transbronchial biopsy are of fundamental importance in the diagnosis of pathologies affecting the lungs of immunosuppressed patients, especially those infected with HIV. This was a descriptive and retrospective study, in which the results of bronchoalveolar lavages, bronchial brushings and transbronchial biopsies of HIV-positive patients attended at the Clinical Hospital of the Federal University of Triangulo Mineiro from 1999 to 2015 were reviewed to determine the most frequent findings in these patients, to evaluate the diagnostic accuracy of these procedures and to correlate bronchoscopy results with clinical and radiological findings. Serological tests for HIV were confirmed and cases with negative or unverified serology were excluded. Medical records were reviewed for correlation with clinical and radiological findings. A total of 1,423 patients with a mean age of 50 years were initially selected; 727 cases had no serology for HIV; 696 had serology for HIV and 64 were positive. Of these, 47 were men, aged 24 to 84 years, and 17 women, aged 31 to 69 years. Biopsies and cytological tests were positive in 20 (31.25%) of the 64 patients and the most frequent diagnosis was pneumocystosis, found in 8 cases (12.5%). Of the 20 bronchofibroscopy-positive patients, only 2 did not show agreement between histopathological and clinical-radiological diagnoses. The analysis of the cytological tests and biopsy specimens obtained by bronchofibroscopy seems to be valuable for the etiological diagnosis of pulmonary infections in HIV- positive patients; however, negative results do not always exclude the diagnosis. In these cases, clinical symptoms and imaging findings may help to guide the best therapy.

The hantavirus cardiopulmonary syndrome is considered an emerging disease in the Americas. Since 1993, thousands of cases have been reported from different countries, but mainly from Brazil. This study aims to describe some epidemiological, clinical and anatomopathological aspects of patients with hantavirus who presented poor outcome and were autopsied in a teaching hospital in Brazil, from 2000 to 2014. Of the 10 patients included, nine were male (mean age 43.5 years) and seven reported previous contact with rodents. Fever was present in eight of ten patients, dyspnea in nine of ten and myalgia in seven of ten patients; hemoconcentration, leukocytosis, thrombocytopenia and renal involvement were evidenced in all the 10 cases. At autopsy, the main alterations were seen in the lungs: pleural effusion (8/10 cases), increased weight 2.5 to 3 times, congestion/edema (10/10), interstitial mononuclear inflammation (10/10), alveolar hemorrhage (7/10), pulmonary collapse (7/10), hyaline membranes (7/10) and alveolar neutrophilic infiltrate (2/10). Pericardial effusion (2/10), mild myocardium inflammation (4/10), right ventricle dilation (1/10), polyploidy nuclei (3/10) and pericardial diffuse petechial (1/10) were also observed. The other organs exhibited discrete and non-specific alterations. Currently, this syndrome continues to be associated with high mortality directly linked to a late diagnosis and/or a misdiagnosis in the medical centers where these patients were seen for the first time. The anatomopathological findings at autopsy revealed the final phase of the process with pulmonary alterations, allowing a direct correlation with the severity of respiratory distress observed in these patients at admission.

Helicobacter pylori ( H. pylori ) is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing H. pylori infection. This study is aimed at analyzing the mRNA expression of the cytokines IFN-γ , IL-17 , IL-10 , TGF-β , IL-6 , IL-22 , IL-23 , and IL-33 ; transcription factors T-bet , RORC , and FOXP3 ; enzymes ARG1 , ARG2 , and NOS2 ; and neuropeptides VIP and TAC and their respective receptors VIPR1 and TACR1 in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the ARG1 gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the TGF-β gene and its FOXP3 transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of IFN-γ , IL-17 , IL-10 , and TGF-β and the transcription factors, T-bet and RORC , in the presence or absence of H. pylori showed no significant difference. However, the expression of FOXP3 was significantly lower in H. pylori -positive patients than that in H. pylori -negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that IL-33 may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.

Background: Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood., Objective: We analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients' clinical and pathological features., Methods: The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique., Results: PIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between PIK3CA mutations and patients' clinical features or TP53 mutation profile., Conclusion: This is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases., Competing Interests: The local ethic committees approved the study (number 1010/2015).Not applicable.The authors declare that they have no competing interests for this present study.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Aim: The molecular pathogenesis of esophageal squamous cell carcinoma (ESCC) has been increasingly studied, but there is no report on the role of MSI in ESCC development associated with chagasic megaesophagus (CM).Results/methodology: In four ESCC/CM (4/19) we found microsatellite instability (MSI) alterations (21.1%), being three MSI-L (15.8%) and one MSI-H (5.3%). Four out of 35 ESCC cases showed MSI-L (11.4%) and only one out of 26 CM cases presented MSI-L (3.9%). The MSI-H was observed in an ESCC/CM patient that presents lack of MSH6 immunostaining corroborating deficiency in MMR pathway. Interestingly, the MSI-H ESCC/CM case also presented a deletion the HSP110 poly(T)17 gene., Discussion/conclusion: Taking together, we concluded that MSI is a rare event in esophageal squamous cell carcinoma, but can be associated with CM.

Objectives: Galectins are mediators that play an important role in the inflammatory response and in this study we analyzed the expression of Galectins (Gal) -1, -3 and -9 in biopsies of the gastric antrum of patients with upper gastrointestinal symptoms., Methodology: 44 patients with upper digestive tract symptoms were evaluated, and underwent Upper Digestive Endoscopy examination. Sections of the gastric antrum were fixed in buffered formaldehyde at 4% in order to perform the anatomopathological examination and immunohistochemical analysis for Galectins-1, -3 and -9 expression. Fresh sections of gastric antrum were used for DNA extraction and evaluation of Helicobacter pylori (H. pylori). P values<0.05 were considered statistically significant., Results: Gal-1 was significantly more expressed on stroma than epithelium (p<0.0001), whereas Gal-3 and Gal-9 were more expressed on epithelium (p<0.0001). Gal-3 was found to be significantly higher in the stroma of patients with H. pylori infection, mainly on Cag-A positive H. pylori (p<0.0001). Gal-9 was down modulated in stroma of patients with chronic gastritis., Conclusion: Up modulation of Gal-3 expression was associated with H. pylori infection and down modulation of Gal-9 with the inflammatory process of chronic gastritis., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases); B - one or two antiretroviral drugs or HAART for less than six months (83 cases); C - HAART for six months or longer (54 cases). In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%), followed by cytomegalovirus (19.2%), Histoplasma capsulatum (6.5%), mycobacteria (5.6%), and Toxoplasma gondii (4.3%). T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV) was more frequent in group A compared with groups B and C (p < 0.05); 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

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., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training., (© The American Society of Tropical Medicine and Hygiene.)

Objective: To compare the diagnostic accuracy of the classic Meisels cytologic criteria and the Schneider secondary criteria relative to the hybrid capture method for diagnosing HPV infection., Methods: This was a retrospective study performed at a public university hospital. A total of 41 patients with a cytologic diagnosis of HPV infection and 40 HPV-negative patients were selected for review of the cervical-vaginal smears seeking to classical and secondary criteria. A single pathologist reviewed the slides in search of the criteria. The classical and secondary cytologic criteria were compared with the hybrid capture for diagnosing HPV infection. Bartleti test was applied for the age analysis, and Fisher's exact test was used to compare proportions. The tests were considered significant when the probability of rejecting the null hypothesis was less than 5% (p < 0.05)., Results: The Meisels criteria were less sensitive (34.0%) than the secondary Schneider criteria (57.5%) when compared with the hybrid capture (p < 0.0001), although the specificity of the former criteria was non-significantly higher (91.2% and 67.7%, respectively). In cases of moderate or intense inflammation, the sensitivity and specificity of the Schneider criteria were decreased, 33.3% and 50.0% respectively (p = 0.0115)., Conclusions: Compared with hybrid capture for diagnosis of HPV infection, the sensitivity of the secondary Schneider criteria was higher than the classical Meisels criteria.Moderate or intense inflammation reduces the sensitivity and specificity of the secondary Schneider criteria for diagnosing HPV infection using the hybrid capture as the gold standard.

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.

Ovarian cancer is the ninth most common malignancy and the fifth leading cause of cancer death in women in the USA. The majority of malignant tumors of the ovary are diagnosed at an advanced stage, making it the most fatal gynecological cancer. The aim of the current study was to determine whether there are differences in immunohistochemical tissue staining of cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) between benign tumors and malignant primary ovarian cancer. In total, 28 patients undergoing surgery for ovarian cysts were evaluated, and a diagnosis of benign neoplasm (n=14) or malignant neoplasm (n=14) was determined. An immunohistochemical study of histological sections of ovarian tumors was conducted. The results were analyzed using Fisher's exact test, with P<0.05 indicating a statistically significant difference. Immunohistochemical staining of IL-10 was increased in malignant tumors compared with benign tumors (P=0.0128). For TNF-α, the immunohistochemical staining was more intense in malignant neoplasms, however, a statistically significant difference was not observed. These results indicate that the analysis of cytokines may be useful as a potential tissue marker of ovarian malignancy.

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.

The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

Objective: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis., Methods: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival., Results: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p=0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p=0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18., Conclusion: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy.

Megaesophagus is one of the major causes of morbidity in chronic Chagas disease, and extensive denervation, associated with an inflammatory process, is recognized as the key factor for alterations in motility and disease development. Here, we analyzed esophagus samples from necropsied, infected individuals--6 cases with megaesophagus and 6 cases without megaesophagus--for the relative areas of expression of 2 neuromediators, substance P and vasoactive intestinal peptide, which are known to activate or inhibit, respectively, local immune cells. Samples from 6 noninfected individuals were used as controls. Esophageal sections were immunohistochemically stained for protein gene product 9.5, vasoactive intestinal peptide, and substance P, and the relative areas of expression of the latter 2 were calculated. Morphometric analyses revealed increased substance P and decreased vasoactive intestinal peptide relative areas in esophageal sections from patients with megaesophagus. Furthermore, in the group of patients without megaesophagus, the loss of vasoactive intestinal peptide positively correlated with the denervation process. We suggest that an imbalance between vasoactive intestinal peptide and substance P production results in the reestablishment and maintenance of the inflammatory process, leading to denervation and, consequently, promoting the development of megaesophagus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

In addition to neurons, interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility with a pacemaker function. This study aimed to quantitatively analyze ICC, neurons, and muscular area, the latter to correct for quantitation errors resulting from dilation in case of a megacolon and from the dispersion of ICC that can be attributed to muscular hypertrophy. We analyzed 30 colon samples: ten chagasic megacolon (CM), ten chagasic colons without megacolon (CXM), and ten nonchagasic control patients (NC). We measured the area of muscularis propria and counted the number of neurons of the myenteric plexus in a histological section of an intestinal ring and the number of ICC at the level of the myenteric plexus and circular muscle layer, the latter in a section immunohistochemically stained for CD117. Muscular hypertrophy occurred only in the CM group. Compared to the NC group, we found in the CM group a statistically significant reduction of 80 % in the number of neurons, 60 % in the number of ICC in the myenteric plexus, and 38 % in the area of circular muscle. In the CXM group, these numbers were highly variable, and their reduction, less pronounced. We conclude that the number of ICC is significantly reduced in CM patients, and that this might contribute to the pathophysiology of CM. However, the development of CM requires severe denervation, whereas CXM generally exhibits less than 50 % denervation, favoring the hypothesis that the reduction in ICC number is, in part, a consequence of denervation.

Involvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.

To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus) and 50 colons (25 with and 25 without megacolon). The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega), the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+), scarce macrophages (CD68+), and rare B lymphocytes (CD20+).

A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies.

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.

Considering that there are some studies with autopsies from AIDS describing only malignant neoplasias and that changes can occur after the introduction of Highly Active Antiretroviral Therapy (HAART), our objectives were to analyze the frequency of benign and malignant neoplasms in AIDS patients in the periods of both pre- and post-HAART. This is a retrospective study with 261 autopsies of HIV-positive patients between 1989 and 2008 in Uberaba, Brazil. Sixty-six neoplasms were found (39 benign, 21 malignant and six premalignant) in 58 patients. The most frequent malignant neoplasms were lymphoid, in 2.7% (four Non-Hodgkin lymphoma, one Hodgkin, one multiple myeloma and one plasmablastic plasmacytoma), and Kaposi's Sarcoma, in 2.3% (six cases). The most frequent benign neoplasms were hepatic hemangiomas in 11 (4.2%) of 261 cases and uterine leiomyoma in 11 (15.7%) of 70 woman. In the pre-HAART period eight (9.8%) benign neoplasias and four (4.9%) malignant occurred in 82 patients; in the post-HAART period, 29 (16.2%) benign and 17 (9.5%) malignant were present; however, the differences were not significant. We conclude that the introduction of HAART in our region doesn't look to have modified the frequency of neoplasms occurring in patients with HIV.

Aims and Background: Cervical intraepithelial neoplasia (CIN) grade II-III is being diagnosed in younger women and, because of the reproductive age range for women and the habits associated with a modern lifestyle, is now affecting a broad age range. Surgical treatment for CIN has been associated with premature amenorrhea, low birth weight, and premature labor and birth. It is therefore imperative to develop clinical treatments for CIN, such as conservative treatment with interferons. The object of the present study was to evaluate the behavior of cytokines (IFN- g, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF β) in the serum of patients with an initial diagnosis of CIN II-III., Methods: Ten patients with CIN-CIN II (60%, n = 6) and CIN III (40%, n = 4), 23 to 51 years of age and who had not received any prior treatments, were evaluated. The patients were given 3 million/UI (per cm2 of colposcopic lesion) of human recombinant IFN-α 2b by intralesional administration (18 applications on alternate days). Before treatment, in the 6th, 12th, and 18th applications, blood was collected from the patients for cytokine analysis using ELISA., Results: Half of the patients had a good pathologic response; the other half, all of whom were smokers, had therapeutic failure. The average concentration of IL-12 (pg/ml) in the serum of patients who responded well to therapy was elevated from the 12th and 18th application of IFN-α 2b compared to patients who experienced therapeutic failure: 1804.0 ± 1020 vs 391.2 ± 722.3 and 1738.0 ± 2426.0 vs 448.5 ± 407.2, respectively, P <0.05., Conclusions: CIN II-III treated with intralesional IFN-α 2b achieved a good response in non-smoking patients and was associated with an increase in IL-12 serum levels.

Purpose: To identify risk factors associated with recurrence of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedures in women with and without human immunodeficiency virus (HIV)., Methods: A total of 33 patients with recurrent CIN and 105 without recurrence were contrasted using a nested case-control design. The patients were enrolled between 1999 and 2004. Recurrence diagnosis was established after conization, and tissues were fixed in formalin and embedded in paraffin. Polymerase chain reaction was used to detect the human papillomavirus genome (HPV DNA) types 6, 11, 16, 18, 31, 33, and 35. Statistical analysis was performed using χ² test with Yates correction and the Fisher's exact test for comparison of categorical variables. Multivariate analysis was carried out using logistic regression models., Results: Human immunodeficiency virus infection (p = 0.001), glandular involvement (p = 0.000), and compromised margins (p = 0.02) were significantly associated with CIN recurrence. HPV DNA was positive in 57.6% of patients with CIN recurrence. High-risk HPV subtypes were detected in most cases but were not associated with recurrence (p = 0.27). In multivariate analysis, HIV infection and glandular involvement were independently associated with CIN recurrence., Conclusions: Human immunodeficiency virus infection and glandular involvement are associated with CIN recurrence.

Introduction: To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking., Methods: 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed., Results: Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031)., Conclusions: ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

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.

Context and Objective: Many factors influence occurrences of vulvovaginitis. The aims here were to assess skin color and age-related differences in the vaginal flora and occurrences of vulvovaginitis., Design and Setting: Cross-sectional study; tertiary referral hospital (Universidade Federal do Triângulo Mineiro, Uberaba)., Methods: Healthy women who underwent routine outpatient gynecological assessments were assessed for vulvovaginitis and vaginal flora and then divided into whites (n = 13,881) and nonwhites (n = 5,295). Statistical analysis was performed using the X² test, logistic regression and odds ratios., Results: The vaginal microflora was skin-color dependent, with greater occurrence of clue cells, Trichomonas vaginalis and coccobacilli in nonwhite women (p < 0.0001). Döderlein bacilli and cytolytic flora were more prevalent in white women (p < 0.0001 and p < 0.05, respectively). The vaginal microflora was age-dependent within the skin color groups. Among the nonwhite women, clue cells were more prevalent in women aged 21 to 50 years; Trichomonas in women up to 40 years and coccobacili in women between 21 and 40 years (P < 0.05). During the proliferative and secretory phases, the nonwhite women were more likely to present clue cells, Trichomonas, Candida and coccobacilli (OR, proliferative phase: 1.31, 1.79, 1.6 and 1.25 respectively; secretory phase: 1.31, 2.88, 1.74 and 1.21 respectively), while less likely to present Döderlein flora (OR, proliferative phase: 0.76; secretory phase: 0.66), compared with white women, irrespective of age., Conclusions: There are differences in vulvovaginitis occurrence relating to skin color, which may be associated with variations in vaginal flora.

Objectives: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma., Methods: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (+/- 4.3), 35.5 (+/- 9.5), and 50 (+/- 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the infiltrating tumor. Two independent observers performed the immunohistochemical analysis., Results: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05)., Conclusion: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

Chagas disease is caused by infestation with the parasite Trypanosoma cruzi, and some patients who are serologically positive develop chronic megaesophagus, whereas others are symptom-free. Gastrointestinal form of Chagas disease involves an inflammatory invasion of the enteric plexuses and degeneration of enteric neurons and previous works related that enteroglial cells would be involved in enteric inflammatory responses. Because of this, the aims of this study were to determine the relation of enteroglial cells with the denervation process in chagasic patients with and without megaesophagus and seronegative individuals. Our results indicated that the innervation of the esophageal muscle was substantially reduced in patients with megaesophagus, but asymptomatic seropositive subjects were not different to seronegative controls. Besides, patients with megaesophagus had significant decreased of enteroglial cells labeled with S-100 and glial fibrillary acidic protein, whereas patients without megaesophagus presented an increased of both labels. We believe that enteroglial cells would operate a mechanism of defense in the enteric nervous system against the Trypanosoma cruzi infection, which could prevent the organ denervation and preserve the esophagus function., (Crown Copyright 2010. Published by Elsevier Inc.)

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).

The objective of the present study was to assess infections and cytologic abnormalities in cervicovaginal smears from 153 HIV-positive women and 169 HIV-negative followed up at the UFTM School of Medicine between May 1999 and May 2002. The medical records and cervicovaginal smears were reviewed and the HIV-positive group was classified according to CD4 cell count, HIV viral load, antiretroviral therapy and HIV subgroups (with or without disease; with or without therapy) and compared to HIV-negative group. We conclude that the frequency of Candida sp, Trichomonas vaginalis and bacterial vaginosis in cervicovaginal smear, is not different between HIV-positive and HIV-negative women, even if the HIV-group is subdivided according to CD4 cell count, HIV viral load, antiretroviral therapy and HIV subgroups. The frequency of LSIL, in cervicovaginal smears, was greater in the HIV-group (17.6%) than in the HIV-negative (4.1%); there was no difference between the two groups according to frequency of HSIL (4.6% versus 1.8%), ASCUS/AGUS (7.8% versus 3.5%) and invasive carcinoma (1.3% versus 0.6%). The frequency of LSIL was greater in the HIV positive group with CD4 cell count < 350 cells/mm(3). The viral load, therapeutic regimen and HIV subgroups (HIV-positive without therapy, HIV-positive with therapy, AIDS by immunological criteria and AIDS by clinical criteria) have not shown relationship with LSIL frequency, until now.

Context: Endemic pemphigus foliaceus, or fogo selvagem, is a chronic autoimmune disease characterized by the formation of intraepidermal blisters that reduce adhesion between keratinocytes. Endemic pemphigus foliaceus is associated with the presence of autoantibodies and high levels of cytokines involved in the inflammatory response., Objectives: To evaluate the expression of the proinflammatory cytokines interleukin 1, interferon gamma, and tumor necrosis factor alpha; the proapoptotic inducers Fas and inducible nitric oxide synthase; and the apoptosis inhibitor Bcl-2; and to evaluate the presence of apoptosis., Design: Skin biopsies from 13 patients with endemic pemphigus foliaceus and controls were evaluated by immunohistochemistry and apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay., Results: Proinflammatory cytokines were only detected in cells of the inflammatory exudate. Inducible nitric oxide synthase, Fas, and Bcl-2 were expressed by both epithelial and inflammatory cells. Epithelial apoptosis was observed in 12 cases (92.3%), and subepithelial apoptosis in 11 cases (85%)., Conclusions: This study suggests that apoptosis as well as the local production of proinflammatory cytokines are associated with endemic pemphigus foliaceus lesions. These results may contribute to the development of new therapeutic approaches to endemic pemphigus foliaceus.

Context: Lesions of the adipose tissue are the most common type of soft-tissue lesion among adults., Case Report: We describe the case of a 33-year-old female patient with a soft-tissue lesion in her left knee that was diagnosed as a hemosiderotic fibrohistiocytic lipomatous lesion. This type of lesion, which was described for the first time in 2000, preferentially affects the ankle region of middle-aged women with a history of previous local trauma. Lesion recurrence is common, caused by incomplete resection, although there have not yet been any reports of metastases. After a review of the literature, we describe the clinical, radiological, morphological and immunohistochemical characteristics, along with their main differential diagnoses.

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.

A case of acquired megacolon in a 62-year-old man with acute abdomen due to sigmoid volvulus is reported. The case was associated with the use of psychiatric medications. The aim in this report was to emphasize the differential diagnosis with Chagas megacolon. Anatomopathological examination did not show any evidence of denervation, ganglionitis and/or myositis, and the serological test for Chagas disease was negative.

Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 microM were more frequent than NO levels <80 microM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis.

This report describes a 32-year-old male AIDS patient. He presented with a clinical picture characterized by severe headache, blurred vision, and fever that had lasted for 10 days. At admission, no remarkable neurologic abnormalities were observed. Cranial tomography showed a ring-enhanced lesion with edema and a mass effect in the right occipital lobe. The initial diagnosis was toxoplasmosis, and treatment of this was administered. However, 5 days later, the patient's clinical status worsened and he died. The necropsy showed necrotizing and hemorrhagic encephalitis, with trophozoites similar to an amoeba species. Furthermore, the kidneys, adrenal glands, thyroid gland, and liver were also involved. The amoeba Balamuthia mandrillaris was identified by an immunofluorescence test.

Introduction: Although studies of risk factor profiles have been conducted to identify biological markers to predict the natural history of cervical intraepithelial neoplasia (CIN) grade III, there is not sufficient information to support the routine clinical use of any biomarker., Objectives: The purpose of this study was to examine aberrant promoter methylation, which is implicated in cancer development and progression, in CIN III lesions in order to identify markers associated with more aggressive biological behavior that could be used to recognize women who are at higher risk of recurrence., Patients and Methods: We used methylation-specific polymerase chain reaction to analyze promoter hypermethylation of 8 genes (p16, RARbeta, GSTP1, MGMT, p14, TIMP3, E-cad and DAPk) in 33 uterine cervix cones with CIN III that were also submitted to human papillomavirus (HPV) genotyping. All 33 patients in this study had been clinically followed after conization with Papanicolaou smears, colposcopy, and biopsy when indicated, every 6 months during 5 years., Results: Of the 33 patients, 12 (36%) underwent immediate hysterectomy after conization for having compromised cone margins, 14 (43%) have not relapsed, and 7 (21%) presented CIN relapse. The frequency of HPV infection in this group was 97% and no significant difference between the groups was observed. HPV of high oncogenic risk was present in 29 (87.9%) cases; HPV 16 was the most frequent (69.7%), while HPV 18 was found in 33.3%; however, it was associated with HPV 16 in 15.1%. Concomitant infection by HPV 6/11 was detected in 21.2% (15.1% with HPV 16 and 6.1 with HPV 18). 85.7% (6/7) of patients with recurrence had HPV 18 vs 0% (0/14) of patients without recurrence (P = 0.0001). At least 1 of the 8 genes was found hypermethylated in all samples. Concomitant hypermethylation of several genes was frequently found. However, CIN relapse was only seen in the cases with hypermethylation of 3 or more of the 8 genes studied (P = 0.0039)., Conclusion: We suggest that aberrant promoter methylation may play a role and may serve as a useful biomarker in the recurrence of CIN.