Male Uro-Rectal Iatrogenic Fistula Treatment in Pelvic Tumours: A National Multi-Institutional Study

Introdução: As fístulas uro-rectais (FUR) constituem uma complicação devastadora do tratamento de tumores pélvicos e um desafio cirúrgico para o cirurgião reconstrutivo. Contudo, apesar da sua crescente incidência associada a uma utilização cada vez mais frequente das diferentes modalidades não-cirúrgicas, especialmente de radioterapia, com ou sem cirurgia, para o tratamento de tumores pélvicos, a fístula urorectal permanece relativamente rara. Dada a elevada improbabilidade do encerramento espontâneo da fístula uro-rectal, a correcção cirúrgica torna-se necessária na quase totalidade dos casos. Apesar da existência de várias técnicas cirúrgicas, as taxas de falência/recorrência são habitualmente elevadas, particularmente em fístulas rádicas. Descrevemos neste estudo a nossa experiência limitada no tratamento de fístulas urorectais resultantes de tratamentos de tumores pélvicos (aparelho urinário inferior e recto). Métodos: Entre Outubro de 2008 e Fevereiro de 2015, foram identificados 12 pacientes do sexo masculino com fístula urorectal e tratados nas nossas instituições. Foi efectuada revisão dos processos clínicos dos pacientes, incluindo a idade, sintomas, presença de comorbilidades, marcha diagnóstica, tipo e etiologia da fístula, tipo de reconstrução cirúrgica, follow-up e resultados. Foram excluídos do estudo todos os pacientes com fístula não-neoplásica/inflamatória. Resultados: Foram identificados e tratados 12 pacientes nas nossas instituições. Um dos pacientes, após ressecção anterior do recto, desenvolveu metástases ganglionares e hepáticas 4 meses após o diagnóstico da fístula urorectal, durante tratamento médico/antibiótico de abcesso pélvico e sua resolução após drenagem e, consequentemente, foi excluído do tratamento cirúrgico e do estudo. A idade média dos doentes era de 68 anos (53 – 78). Nove pacientes desenvolveram fístula uro-rectal após terapêutica de carcinoma da próstata): Dois após braquiterapia de baixa dosagem combinada com radioterapia externa; cinco após prostatectomia radical retropúbica (PRR), com radioterapia externa adjuvante em um; um após braquiterapia de baixa dosagem seguida de ressecção transuretral por obstrução prostática; e um após ultra-som focalizado de alta intensidade e radioterapia externa. Em dois pacientes, a fístula resultou de tratamento cirúrgico de carcinoma rectal, associado a radioterapia externa em um deles. Foi efectuada em todos os pacientes derivação fecal com colostomia e derivação urinária, ou com cateterização suprapúbica, ou com cateterização uretral durante o período de espera para a reconstrução cirúrgica. Não houve encerramento espontâneo de fístula urorectal em nenhum paciente. Onze pacientes foram submetidos a reconstrução cirúrgica. Foi utilizada abordagem exclusivamente perineal em sete doentes e abdominoperineal em quatro. Obteve-se encerramento eficaz da fístula em seis pacientes à primeira tentativa cirúrgica, dois doentes necessitaram uma segunda tentativa, enquanto que em um doente foram necessárias três tentativas cirúrgicas (duas delas em outras instituições) de forma a atingir um resultado com sucesso. Ocorreu falência cirúrgica em dois doentes, os quais, actualmente, não desejam qualquer tentativa reconstrutiva adicional. Estes dois doentes e um doente, em quem a reconstrução foi eficaz, permanecem ainda com colostomia. O tempo médio de follow- -up foi de 25,5 meses (3-75). Conclusão: As fístulas uro-rectais são uma complicação pouco frequente, mas devastadora, do tratamento dos tumores pélvicos, habitualmente associada com morbilidade debilitante e degradação da qualidade de vida. Embora a sua reconstrução cirúrgica possa ser extremamente difícil, ela é possível com sucesso na maioria dos casos através de uma abordagem perineal ou abdominoperineal agressiva e interposição de tecidos, quando indicada.info:eu-repo/semantics/publishedVersio

Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice

PMCID: PMC3579848This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Maternal and neonatal factors related to prematurity

ABSTRACT OBJECTIVE To identify maternal and neonatal factors associated with prematurity in the municipality of Porto Alegre. METHOD This was a population-based case-control study. The cases were newborns under 37 weeks of gestation and the controls were newborns over 37 weeks. The data came from the records of 19,457 births in the city of Porto Alegre in the year 2012 from the Information System on Live Births of the Municipal Health Department. The analysis was carried outand adjusted by a Logistic Regression according to a hierarchical model. The variables studied were allocated into three hierarchy levels: sociodemographic variables; reproductive history; and gestational and birth factors. RESULTS There were 767 cases allocated and 1,534 controls in a design of a case for two controls (1:2) by simple randomization. In the final model, a statistically significant association was found for prematurity for the following variables: mother's age under 19 years old (OR=1.32; CI 95%: 1.02-1.71) or over 34 years old (OR=1.39; CI 95%: 1.12-1.72); inadequate maternal schooling for age (OR=2.11; CI 95%: 1.22-3.65); multiple pregnancies (OR=1.14; CI 95%: 1.01-1.29); C-section (OR=1.15; CI 95%: 1.03-1.29); birth weights under 2,500g (OR=4.04; CI 95%: 3.64-4.49); Apgar score at five minutes between zero and three (OR=1.47; CI 95%: 1.12-1.91); and inadequate prenatal care (OR=1.18; CI 95%: 1.02-1.36). CONCLUSION The present study showed the most immediate consequence of prematurity for newborns by evidencing its association with worse Apgar scores and low birth weight. The following factors were also shown as possible more distal determinants of prematurity: mother's age; inadequate maternal education; multiple gestation; inadequate prenatal care; and C-section

Bone mineral density and body composition in postmenopausal women with psoriasis and psoriatic arthritis

Introduction: the aim of the present study was to compare bone mineral density (BMD) and body composition (BC) measurements as well as identify risk factors for low BMD and osteoporotic fractures in postmenopausal women with psoriasis (Ps) and psoriatic arthritis (PsA).Methods: A cross-sectional study was carried out in 45 PsA women, 52 Ps women and 98 healthy female controls (HC). Clinical risk factors for low bone density and osteoporotic fracture were evaluated by a specific questionnaire. An X-ray absorptiometry (DXA) at the lumbar spine, total femur and total body was performed on all patients. Skin and joint outcomes were measured by specific tools (PASI, HAQ and DAS28). Morphometric vertebral fractures were evaluated by lumbar and thoracic spine X-ray, according to Genant's method.Results: There were no significant differences in age, body mass index (BMI), total lean mass and bone mineral density among the groups. However, the PsA group had a significantly higher body fat percentage (BF%) than the Ps and HC groups. Osteoporotic fractures were more frequently observed in PsA and Ps groups than in the HC group (P = 0.01). Recurrent falls and a longer duration of disease increased the risk of fracture (odds ratio (OR) = 18.3 and 1.08, respectively) in the PsA group (P = 0.02). Disability was the main factor related to osteoporotic fracture in the Ps group (odds ratio (OR) = 11.1) (P = 0.02).Conclusions: Ps and PsA patients did not present lower BMD. However, they had a higher prevalence of osteoporotic fractures and higher risk of metabolic syndrome. Patients with a longer duration of disease, disability and recurrent falls need preventive measures.Rheumatology Division at UNIFESP/EPMUniversidade Federal de São Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 São Paulo, BrazilWeb of Scienc

Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response

Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

<p>Abstract</p> <p>Background</p> <p>Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome.</p> <p>Methods</p> <p>Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed.</p> <p>Results</p> <p>Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson).</p> <p>Conclusions</p> <p>The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.</p