Telomere length has been shown to be a critical determinant of T cell replicative capacity and in vivo persistence in humans. We evaluated telomere lengths in virus-specific T cells to understand how they may both shape and be changed by the maintenance of memory T cells during a subsequent virus re-infection or reactivation. We used longitudinal peripheral blood samples from healthy donors and samples from a long-term HCV clinical interferon therapy trial to test our hypotheses. To assess T cell telomere lengths, I developed novel modifications to the flow cytometry fluorescence in situ hybridization (flowFISH) assay. These flowFISH modifications were necessary to enable quantification of telomere length in activated, proliferating T cells. Adoption of a fixation-permeabilization protocol with RNA nuclease treatment prior to telomere probe hybridization were required to produce telomere length estimates that were consistent with a conventional telomere restriction fragment length Southern blot assay. We hypothesized that exposure to a non-recurring, acute virus infection would produce memory T cells with longer telomeres than those specific for recurring or reactivating virus infections. We used two acute viruses, vaccinia virus (VACV) and influenza A virus (IAV) and two latent-reactivating herpesviruses, cytomegalovirus (CMV) and varicella zoster virus (VZV) for these studies. Combining a proliferation assay with flowFISH, I found telomeres in VACV-specific CD4 + T cells were longer than those specific for the recurring exposure IAV; data which support my hypothesis. Counter to my hypothesis, CMV-specific CD4 + T cells had longer telomeres than IAV-specific CD4 + T cells. We assessed virus-specific CD4 + T cell telomere length in five donors over a period of 8-10 years which allowed us to develop a linear model of average virus-specific telomere length changes. These studies also found evidence of long telomere, virus-specific CD45RA + T cell populations whose depletion may precede an increased susceptibility to latent virus reactivation. I tested the hypothesis that type I interferon therapy would accelerate T cell telomere loss using PBMC samples from a cohort of chronic hepatitis C virus patients who either did or did not receive an extended course of treatment with interferon-alpha. Accelerated telomere losses occurred in naïve T cells in the interferon therapy group and were concentrated in the first half of 48 months of interferon therapy. Steady accumulation of CD57 + memory T cells in the control group, but not the therapy group, suggested that interferon also accelerated memory turnover. Based on our data, I present proposed models of memory T cell maintenance and impacts of T cell telomere length loss as we age.

Pancreatic cancer is the 4th leading cause of cancer related death in the United States with a median survival time of less than 6 months. Pancreatic ductal adenocarcinoma (PDAC) accounts for greater than 85% of all pancreatic cancers, and is marked by early and frequent mutation of the KRAS oncogene, with activating KRAS mutations present in over 90% of PDAC. To date, though, targeting activated KRAS for cancer treatment has been very difficult, and targeted therapies are currently being sought for the downstream effectors of activated KRAS. Activation of KRAS stimulates multiple signaling pathways, including the MEK-ERK and PI3K-AKT signaling cascades, but the role of downstream effectors in pancreatic tumor initiation and progression remains unclear. I therefore used primary pancreatic ductal epithelial cells (PDECs), the putative cell of origin for PDAC, to determine the role of specific downstream signaling pathways in KRAS activated pancreatic tumor initiation. As one third of KRAS wild type PDACs harbor activating mutations in BRAF , and KRAS and BRAF mutations appear to be mutually exclusive, I also sought to determine the effect of activated BRAF (BRAF V600E ) expression on PDECs and the signaling requirements downstream of BRAF. I found that both KRAS G12D and BRAF V600E expressing PDECs displayed increased proliferation relative to GFP expressing controls, as well as increased PDEC survival after challenge with apoptotic stimuli. This survival was found to depend on both the MEK-ERK and PI3K-AKT signaling cascades. Surprisingly, I found that this survival is also dependent on the IGF1R, and that activation of PI3K/AKT signaling occurs downstream of MEK/ERK activation, and is dependent on signaling through the IGF1R. Consistent with this, I find increased IGF2 expression in KRAS G12D and BRAF V600E expressing PDECs, and show that ectopic expression of IGF2 rescues survival in PDECs with inhibited MEK, but not PI3K. Finally, I showed that the expression of KRAS G12D or BRAF V600E in PDECs lacking both the Ink4a/Arf and Trp53 tumor suppressors is sufficient for tumor formation following orthotopic transplant of PDECs, and that IGF1R knockdown impairs KRAS and BRAF-induced tumor formation in this model. In addition to these findings within PDECs, I demonstrate that KRAS G12D or BRAF V600E expressing tumor cell lines differ in MEK-ERK and PI3K-AKT signaling from PDECs. In contrast to KRAS G12D or BRAF V600E expressing PDECs, activation of AKT at serine 473 in the KRAS G12D or BRAF V600E expressing tumor cell lines does not lie downstream of MEK, and only the inhibition of PI3K alone or both MEK and the IGF1R simultaneously results in loss of tumor cell line survival. However, inhibition of MEK, PI3K, or the IGF1R in KRAS G12D or BRAF V600E expressing tumor cell lines also resulted in decreased proliferation relative to DMSO treated cells, demonstrating that all three signaling cascades remain important for tumor cell growth and are therefore viable options for pancreatic cancer therapeutics.

A rising problem in agriculture is the increase of antibiotic-resistant Salmonella cases associated with chicken eggs, which transmit infection to humans. To counter this, new approaches to combat Salmonella in chickens and desiccated on eggshells are vital in the prevention of human foodborne illness. Disrupting signaling pathways with naturally occurring compounds provides a potential novel avenue for prevention of Salmonella infections, as this would disrupt sensing of these environments and inhibit subsequent optimal gene expression. Starting with signals identified in previous studies, salicylic acid was found to inhibit Salmonella desiccation survival on both eggshells and plastic. To expand upon this, a desiccation inhibition screen of 285 signals resulted in 9 additional potential desiccation inhibitors, including deoxyribose and guanine. By using natural signals to disrupt bacterial communication pathways, novel therapeutics that serve as viable antibacterial alternatives could be developed to prevent Salmonella contamination at a major source.

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n=8), 22 g fructose, 16 g fat and 300 kcal (HFF2-N; n=8), CON + probiotic (CON-P; n=6), or HFF2 + probiotic (HFF2-P; n=6) every 6 h for 70 d. The probiotic mixture (6.2 × 104 cfu/mL) contained Pediococcus acidilactici, Pediococcus pentosaceus, Lactobacillus plantarum and Bacillus amyloliquefaciens. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 40 and 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver and skeletal muscle (longissimus dorsi) were collected on d 70 for histology, triacylglyceride (TAG) quantification, relative gene expression, and Western blot analysis. Metabolomic analysis was performed on liver tissue and plasma. Body weight was not significantly greater in HFF fed pigs compared to CON. Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF2-N and HFF2-P. Livers in HFF2-P and HFF2-N had higher relative weight and TAG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). A probiotic affect was seen as pigs fed CON-P and HFF2-P had higher insulin and HOMA values were increased (P ≤ 0.05). Western blot analysis showed dysregulation of autophagy in liver of pigs fed CON-P and HFF2-P, and in skeletal muscle of pigs fed CON-N and HFF2-N. Metabolomic analysis demonstrated dysregulation of one-carbon metabolism, the tricarboxylic acid cycle (TCA), the urea cycle, and amino acid metabolism of pigs fed HFF2 diets compared to CON diets. In conclusion, Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Furthermore, probiotic supplementation did not ameliorate the onset of NAFLD when fed in conjunction with a HFF diet.

Introdução: obstrução gastroduodenal maligna é uma condição frequente em neoplasias gástricas e pancreáticas em estágio avançado. O tratamento paliativo visa a melhora dos sintomas e da qualidade de vida, sendo realizado pelas técnicas cirúrgicas ou endoscópicas. Embora a terapêutica cirúrgica seja consagrada, as complicações relacionadas ao procedimento e as condições clínicas desfavoráveis dos pacientes devem ser consideradas. Apesar dos avanços do tratamento endoscópico e da possibilidade de oferecer um tratamento menos invasivo, deve-se considerar as complicações e a taxa de reintervenção desta modalidade terapêutica. Novas tecnologias foram desenvolvidas para minimizar as complicações relacionadas ao uso de próteses e demandam uma análise pormenorizada. O objetivo desta revisão sistemática é comparar o tratamento endoscópico com próteses cobertas e não cobertas e o cirúrgico com gastrojejunoanastomose para obstrução gastroduodenal. Métodos: ensaios clínicos randomizados foram identificados nas bases de dados do MEDLINE, Embase, Cochrane, LILACS, SCOPUS e CINAHL. A comparação entre as próteses metálicas cobertas e não cobertas incluiu o sucesso técnico, sucesso clínico, complicações, obstrução, migração, sangramento, perfuração, fratura das próteses e reintervenção. Os desfechos usados na comparação da terapêutica cirúrgica com gastrojejunoanastomose e endoscópica com próteses foram o sucesso técnico, complicações e reintervenção. A avaliação da patência não pode ser incluída devido à falta de uniformidade dos dados extraídos. Resultados: oito artigos foram selecionados, três comparando gastrojejunostomia e próteses e cinco comparando próteses cobertas e não cobertas. A metanálise dos estudos sobre gastroenteroanastomose e próteses não demonstrou diferença significativa no sucesso técnico e número absoluto de complicações. O tratamento com próteses apresentou uma maior taxa de reintervenção que a terapêutica cirúrgica (DR = 0,26, IC 95% = 0,05 a 0,47, NNH = 4). A metanálise que comparou próteses metálicas cobertas e não cobertas não demonstrou diferença estatística significativa considerando o sucesso técnico, sucesso clínico, complicações, fratura das próteses, perfuração, sangramento e necessidade de reintervenção. Uma maior taxa de migração foi atribuída à terapêutica com próteses cobertas (DR = 0,09, IC 95% = 0,04 a 0,14, NNH = 11). Entretanto, o tratamento com próteses cobertas apresenta menor taxa de obstrução em relação às não cobertas (DR = -0,21, IC 95% = -0,27 a -0,15, NNT = 5). Uma análise de subgrupo de estudos com próteses metálicas que incluíram apenas pacientes com câncer gástrico demonstrou resultado semelhante à metanálise com todos os artigos. Conclusões: o tratamento endoscópico paliativo da obstrução gastroduodenal maligna com próteses cobertas apresenta maior taxa de migração e menor número de obstruções quando comparado com o uso de próteses não cobertas. A terapêutica cirúrgica com gastrojejunoanastomose associa-se a uma menor taxa de reintervenção em relação ao uso de próteses / Introduction: malignant gastric outlet obstruction is a frequent condition in advanced gastric and pancreatic neoplasms. Palliative treatment can be performed by endoscopic or surgical techniques. Palliation aims to relief symptoms and increase quality of life. Although surgical therapy is the established treatment, the complication rate of the procedure and the unfavorable clinical conditions must be considered. Despite the advances in the endoscopic treatment and the possibility to offer a minimally invasive therapy, complication rate and need of reintervention must be reminded. New technologies have been developed to minimize the complications related to the use of stents and require a detailed analysis. This systematic review aims to compare surgery and covered and uncovered stent treatments for gastric outlet obstruction. Methods: randomized clinical trials were identified in MEDLINE, Embase, Cochrane, LILACs, BVS, SCOPUS and CINAHL databases. Comparison of covered and uncovered stents included: technical success, clinical success, complications, obstruction, migration, bleeding, perforation, stent fracture and reintervention. The outcomes used to compare Gastrojejunostomy and stents were technical success, complications and reintervention. Patency rate could not be included because of lack of uniformity of the extracted data. Results: eight studies were selected, three comparing gastrojejunostomy and stents and five comparing covered and uncovered stents. The meta-analysis of surgical and endoscopic stent treatment showed no difference in the technical success and overall number of complications. Stents had higher reintervention rates than surgery (RD: 0.26, 95% CI [0.05, 0.47], NNH: 4). There is no significant difference in technical success, clinical success, complications, stent fractures, perforation, bleeding and the need for reintervention in the analyses of covered and uncovered stents. There is a higher migration rate in the covered stent therapy compared to uncovered self-expanding metallic stents in the palliation of malignant gastric outlet obstruction (RD: 0.09, 95% CI [0.04, 0.14], NNH: 11). Nevertheless, covered stents had lower obstruction rates (RD: -0.21, 95% CI [-0.27, - 0.15], NNT: 5). A subgroup analysis with studies that included only patients with gastric cancer showed similar results when compared with the analysis with all trials. Conclusions: in the palliation of malignant gastric outlet obstruction, covered stents had higher migration and lower obstruction rates when compared with uncovered stents. Gastrojejunostomy is associated with lower reintervention rates than stents

Os desfechos clínicos e oncológicos dos pacientes submetidos à ressecção endoscópica do câncer gástrico precoce (CGP), considerando os critérios de indicação, comparados à cirurgia, não foram relatados em revisões sistemáticas. A pesquisa foi desenvolvida para estabelecer os desfechos de curto e longo prazos da ressecção endoscópica comparada à cirurgia no tratamento do CGP, elevando as informações para o nível de evidência 2a, melhor respaldando a prática clínica. A revisão sistemática com metanálises foi procedida utilizando-se as bases Medline, Embase, Cochrane, LILACS, Scopus e CINAHL. Onze coortes retrospectivas foram selecionadas para análise qualitativa e quantitativa. Todos os estudos incluem pacientes com CGP e comparam os desfechos nos dois braços. Os dados envolveram 2654 pacientes que preenchiam os critérios absolutos ou expandidos para ressecção endoscópica. Diferentes modalidades de tratamento endoscópico foram avaliadas, principalmente os procedimentos de ressecção, como endoscopic mucosal resection (EMR) e endoscopic submucosal dissection (ESD). As informações basearam-se nas características dos participantes, critérios de inclusão e exclusão, tipos de intervenções e desfechos (diferentes taxas de sobrevida, eventos adversos, ressecção completa, recorrência e mortalidade). As análises dos riscos absolutos dos desfechos foram feitas com o software RevMan, computando-se as diferenças de risco (DR) das variáveis dicotômicas. Dados de DR e intervalo de confiança de 95% (IC) foram calculados utilizando-se o teste de Mantel-Haenszel e a inconsistência foi qualificada e reportada em ?2 e método Higgins (I2). A análise de sensibilidade foi feita quando a heterogeneidade era maior que 50%. Todas as análises basearam-se inicialmente no modelo de efeito fixo. Dados de sobrevida de 3 anos estavam disponíveis em seis estudos (n = 1197). Não houve DR após os dois tratamentos (DR = 0,01, IC 95% = -0,02 a 0,05). A sobrevida de 5 anos (n = 2310) não demonstrou diferença significativa entre os grupos analisados (DR = 0,01, IC 95% = -0,01 a 0,03). A avaliação de 551 pacientes não evidenciou desigualdade na sobrevida de 10 anos entre as diferentes abordagens (DR = -0,02, IC 95% = -0,15 a 0,10). Dados de complicação estavam presentes em oito estudos (n = 2439), e diferença significativa foi detectada (DR = -0,08, IC 95% = -0,10 a -0,05), demonstrando melhores resultados com a endoscopia. As taxas de ressecção completa foram analisadas em 536 pacientes. Evidenciou-se diferença significativa entre o tratamento endoscópico e cirúrgico (DR = -0,13, IC 95% = -0,17 a -0,09), validando melhores resultados no último grupo. A recorrência foi avaliada em cinco pesquisas (n = 1331) e não houve diferença entre as duas formas de terapêutica (DR = 0,01, IC 95% = -0,00 a 0,02). As taxas de mortalidade foram obtidas de quatro estudos (n = 1107), e não se evidenciou diferença entre os grupos envolvidos (DR = -0,01, IC 95% = -0,02 a 0,00). Conclui-se que as taxas de sobrevida de 3, 5 e 10 anos, recorrência e mortalidade são semelhantes em ambos os grupos. Considerando-se as taxas de complicação, a abordagem endoscópica confere resultados mais apropriados e, analisando-se as taxas de ressecção completa, ela é inferior à cirurgia / Clinical and oncological outcomes of endoscopic resection of early gastric cancer (EGC), considering the indication criteria, compared to surgery, have not been reported in systematic reviews. To address the short- and long-term outcomes of endoscopic resection compared to surgery in the treatment of EGC, a systematic review was performed, establishing the available data to an unpublished 2a strength of evidence, better handling clinical practice. A systematic review and meta-analysis using Medline, Embase, Cochrane, LILACS, Scopus and CINAHL databases were done. Eleven retrospective cohort studies were selected to quantitative and qualitative synthesis. All studies included patients diagnosed with EGC that compared outcomes considering endoscopic treatment and surgery. The included records involved 2654 patients with EGC that filled the standard or expanded indications for endoscopic resection. Different endoscopic treatment modalities were analyzed, mainly mucosal resection procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), compared to surgery. Information of the selected studies was extracted on characteristics of trial participants, inclusion and exclusion criteria, types of interventions and outcomes (different survival rates, adverse events, complete resection, recurrence and mortality rates). The analysis of the absolute risks of the outcomes was performed using the software RevMan, by computing risk differences (RD) of dichotomous variables. Data on RD and 95% confidence interval (CI) for each outcome were calculated using the Mantel-Haenszel test and inconsistency was qualified and reported in X2 and the Higgins method (I2). Sensitivity analysis was performed when heterogeneity was higher than 50%. All pooled analyses were initially based on fixed-effects model. Three-year survival data were available for six studies (n = 1197). There were no RD in 3-year survival data after endoscopic and surgical treatment of EGC (RD = 0.01, 95% CI = -0.02 to 0.05). Five-year survival data (n = 2310) showed no evidence of a difference between the two groups (RD = 0.01, 95% CI = -0.01 to 0.03). The data analysis, in 551 patients, showed no difference in 10-year survival rates between the approaches (RD = -0.02 and 95% CI = -0.15 to 0.10). Complication data were identified in eight studies (n = 2439). A significant difference was detected (RD = -0.08, 95% CI = -0.10 to -0.05), demonstrating better results with endoscopic approach. Complete resection data was analyzed in 536 patients. It showed significant difference in complete resection rates between endoscopic and surgical treatment of EGC (RD = -0.13, 95% CI = -0.17 to -0.09), exhibiting improved results in the surgical group. Recurrence data were analyzed in five studies (n = 1331) and there was no difference between the approaches (RD = 0.01, 95% CI = -0.00 to 0.02). Mortality data were obtained in four studies (n = 1107), and there was no difference between treatment modalities (RD = -0.01, 95% CI = -0.02 to 0.00). This systematic review concludes that 3-, 5- and 10-year survival, recurrence and mortality rates are similar for both groups. Considering procedure-related complication rates, endoscopic approach achieves significantly better results and, analyzing complete resection data, it is considered worse than surgery

No presente estudo, 30 pacientes, do sexo masculino com idade mediana de 29 anos, portadores de hérnias inguinais / inguino-escrotais, unilaterais, indiretas e primárias, sem encarceramento ou estrangulamento, foram submetidos à hernioplastia inguinal, por meio de inguinotomia, sob raqui-anestesia em regime de internação hospitalar. A técnica de correção utilizada foi a de Bassini modificada, sendo que estas modificações repousam no tipo da incisão, abordagem da fáscia transversalis e no reforço da parede posterior do canal inguinal. Os objetivos foram os de avaliar os resultados do pós-operatório mediato quanto aos eventos: intensidade e duração da dor pós-operatória e o tempo de retorno às atividades normais, estabelecendo assim a duração maior ou menor do período de convalescença. Das hérnias operadas 33,33% e 66,67% foram classificadas no intra-operatório como tipos I e II de Nyhus, respectivamente. A duração da cirurgia variou entre 45 e 85 minutos, com média de 66,46 minutos e mediana de 66,5 minutos. A permanência hospitalar foi menor que 24 horas. O índice de mortalidade foi nulo e o seguimento foi feito no 10º e 30° dias de pós-operatório. A intensidade média da dor pós-operatória atingiu seu pico máximo no 1º dia, alcançando 2,93 na escala analógica decimal, sendo que a partir do 5° dia de pós-operatório se tornou insignificante. O retorno às atividades habituais e sociais se deu em um período médio de 5,34 dias. O tempo de retorno ao trabalho alcançou a média de 11,23 dias e mediana de 5 dias. Observou-se complicação leve em dois pacientes (6,67%), que apresentaram edema de bolsa escrotal de rápida resolução. Não se observou complicações infecciosas apesar do não uso de antimicrobianos. A análise dos dados obtidos permite concluir que o procedimento é exeqüível, com boa aceitação por parte dos pacientes, apresentando resultados comparáveis aos obtidos na literatura / In the present study, 30 patients, of the male sex, with an average age of 29, victims of inguinal hernias/ inguino-scrotum, unilateral, indirect and primaries, without confinement or strangulation, were submitted to inguinal hernioplasty, thru inguinotomy, under rachianesthesia on a regimen as hospital in--patients. The correction technique used was the modified- Bassini, since these modifications lie in the kind of incision, approaching of the fascia transversalis and in the reinforcement of the posterior wall of the inguinal duct. The purposes were of evaluating the mediate post-operative results as to the events: intensity and duration of the post-operative pain in the period of time of return to the normal activities, thus determining the longer or shorter duration of the recovery period. Among the operated hernias 33.33% and 66.67% they were classified in the intra-operative as types I and II of Nyhus, respectively. The duration of the surgery varied between 45 and 85 minutes, with an average of 66.46 minutes and median of 66.5 minutes. The in-patients stay in the hospital was less than 24 hours. The mortality rate was null and the follow up was made on the 10th and 30th days of the post operative. The average intensity of the post-operative pain reached its appex on the 1st day, reaching 2.93 in the decimal analogical scale, and as of the 5th day of the post-operative it became insignificant. The return both to the usual and social activities happened in an average period of time of 5.34 days. The period of time of returning to work reached an average of 11.23 days and a median of 5 days. A slight complication was observed in two patients (6.67%), who had edema in the scrotum pouch of fast solution. No infectious complications were detected in spite of not using any anti-microbians. The analysis of the data obtained allow to conclude that the procedure is feasible, with good approval on the part of the patients, presenting results comparable to the ones obtained in the literature

Introdução: obstrução gastroduodenal maligna é uma condição frequente em neoplasias gástricas e pancreáticas em estágio avançado. O tratamento paliativo visa a melhora dos sintomas e da qualidade de vida, sendo realizado pelas técnicas cirúrgicas ou endoscópicas. Embora a terapêutica cirúrgica seja consagrada, as complicações relacionadas ao procedimento e as condições clínicas desfavoráveis dos pacientes devem ser consideradas. Apesar dos avanços do tratamento endoscópico e da possibilidade de oferecer um tratamento menos invasivo, deve-se considerar as complicações e a taxa de reintervenção desta modalidade terapêutica. Novas tecnologias foram desenvolvidas para minimizar as complicações relacionadas ao uso de próteses e demandam uma análise pormenorizada. O objetivo desta revisão sistemática é comparar o tratamento endoscópico com próteses cobertas e não cobertas e o cirúrgico com gastrojejunoanastomose para obstrução gastroduodenal. Métodos: ensaios clínicos randomizados foram identificados nas bases de dados do MEDLINE, Embase, Cochrane, LILACS, SCOPUS e CINAHL. A comparação entre as próteses metálicas cobertas e não cobertas incluiu o sucesso técnico, sucesso clínico, complicações, obstrução, migração, sangramento, perfuração, fratura das próteses e reintervenção. Os desfechos usados na comparação da terapêutica cirúrgica com gastrojejunoanastomose e endoscópica com próteses foram o sucesso técnico, complicações e reintervenção. A avaliação da patência não pode ser incluída devido à falta de uniformidade dos dados extraídos. Resultados: oito artigos foram selecionados, três comparando gastrojejunostomia e próteses e cinco comparando próteses cobertas e não cobertas. A metanálise dos estudos sobre gastroenteroanastomose e próteses não demonstrou diferença significativa no sucesso técnico e número absoluto de complicações. O tratamento com próteses apresentou uma maior taxa de reintervenção que a terapêutica cirúrgica (DR = 0,26, IC 95% = 0,05 a 0,47, NNH = 4). A metanálise que comparou próteses metálicas cobertas e não cobertas não demonstrou diferença estatística significativa considerando o sucesso técnico, sucesso clínico, complicações, fratura das próteses, perfuração, sangramento e necessidade de reintervenção. Uma maior taxa de migração foi atribuída à terapêutica com próteses cobertas (DR = 0,09, IC 95% = 0,04 a 0,14, NNH = 11). Entretanto, o tratamento com próteses cobertas apresenta menor taxa de obstrução em relação às não cobertas (DR = -0,21, IC 95% = -0,27 a -0,15, NNT = 5). Uma análise de subgrupo de estudos com próteses metálicas que incluíram apenas pacientes com câncer gástrico demonstrou resultado semelhante à metanálise com todos os artigos. Conclusões: o tratamento endoscópico paliativo da obstrução gastroduodenal maligna com próteses cobertas apresenta maior taxa de migração e menor número de obstruções quando comparado com o uso de próteses não cobertas. A terapêutica cirúrgica com gastrojejunoanastomose associa-se a uma menor taxa de reintervenção em relação ao uso de próteses / Introduction: malignant gastric outlet obstruction is a frequent condition in advanced gastric and pancreatic neoplasms. Palliative treatment can be performed by endoscopic or surgical techniques. Palliation aims to relief symptoms and increase quality of life. Although surgical therapy is the established treatment, the complication rate of the procedure and the unfavorable clinical conditions must be considered. Despite the advances in the endoscopic treatment and the possibility to offer a minimally invasive therapy, complication rate and need of reintervention must be reminded. New technologies have been developed to minimize the complications related to the use of stents and require a detailed analysis. This systematic review aims to compare surgery and covered and uncovered stent treatments for gastric outlet obstruction. Methods: randomized clinical trials were identified in MEDLINE, Embase, Cochrane, LILACs, BVS, SCOPUS and CINAHL databases. Comparison of covered and uncovered stents included: technical success, clinical success, complications, obstruction, migration, bleeding, perforation, stent fracture and reintervention. The outcomes used to compare Gastrojejunostomy and stents were technical success, complications and reintervention. Patency rate could not be included because of lack of uniformity of the extracted data. Results: eight studies were selected, three comparing gastrojejunostomy and stents and five comparing covered and uncovered stents. The meta-analysis of surgical and endoscopic stent treatment showed no difference in the technical success and overall number of complications. Stents had higher reintervention rates than surgery (RD: 0.26, 95% CI [0.05, 0.47], NNH: 4). There is no significant difference in technical success, clinical success, complications, stent fractures, perforation, bleeding and the need for reintervention in the analyses of covered and uncovered stents. There is a higher migration rate in the covered stent therapy compared to uncovered self-expanding metallic stents in the palliation of malignant gastric outlet obstruction (RD: 0.09, 95% CI [0.04, 0.14], NNH: 11). Nevertheless, covered stents had lower obstruction rates (RD: -0.21, 95% CI [-0.27, - 0.15], NNT: 5). A subgroup analysis with studies that included only patients with gastric cancer showed similar results when compared with the analysis with all trials. Conclusions: in the palliation of malignant gastric outlet obstruction, covered stents had higher migration and lower obstruction rates when compared with uncovered stents. Gastrojejunostomy is associated with lower reintervention rates than stents

Os desfechos clínicos e oncológicos dos pacientes submetidos à ressecção endoscópica do câncer gástrico precoce (CGP), considerando os critérios de indicação, comparados à cirurgia, não foram relatados em revisões sistemáticas. A pesquisa foi desenvolvida para estabelecer os desfechos de curto e longo prazos da ressecção endoscópica comparada à cirurgia no tratamento do CGP, elevando as informações para o nível de evidência 2a, melhor respaldando a prática clínica. A revisão sistemática com metanálises foi procedida utilizando-se as bases Medline, Embase, Cochrane, LILACS, Scopus e CINAHL. Onze coortes retrospectivas foram selecionadas para análise qualitativa e quantitativa. Todos os estudos incluem pacientes com CGP e comparam os desfechos nos dois braços. Os dados envolveram 2654 pacientes que preenchiam os critérios absolutos ou expandidos para ressecção endoscópica. Diferentes modalidades de tratamento endoscópico foram avaliadas, principalmente os procedimentos de ressecção, como endoscopic mucosal resection (EMR) e endoscopic submucosal dissection (ESD). As informações basearam-se nas características dos participantes, critérios de inclusão e exclusão, tipos de intervenções e desfechos (diferentes taxas de sobrevida, eventos adversos, ressecção completa, recorrência e mortalidade). As análises dos riscos absolutos dos desfechos foram feitas com o software RevMan, computando-se as diferenças de risco (DR) das variáveis dicotômicas. Dados de DR e intervalo de confiança de 95% (IC) foram calculados utilizando-se o teste de Mantel-Haenszel e a inconsistência foi qualificada e reportada em ?2 e método Higgins (I2). A análise de sensibilidade foi feita quando a heterogeneidade era maior que 50%. Todas as análises basearam-se inicialmente no modelo de efeito fixo. Dados de sobrevida de 3 anos estavam disponíveis em seis estudos (n = 1197). Não houve DR após os dois tratamentos (DR = 0,01, IC 95% = -0,02 a 0,05). A sobrevida de 5 anos (n = 2310) não demonstrou diferença significativa entre os grupos analisados (DR = 0,01, IC 95% = -0,01 a 0,03). A avaliação de 551 pacientes não evidenciou desigualdade na sobrevida de 10 anos entre as diferentes abordagens (DR = -0,02, IC 95% = -0,15 a 0,10). Dados de complicação estavam presentes em oito estudos (n = 2439), e diferença significativa foi detectada (DR = -0,08, IC 95% = -0,10 a -0,05), demonstrando melhores resultados com a endoscopia. As taxas de ressecção completa foram analisadas em 536 pacientes. Evidenciou-se diferença significativa entre o tratamento endoscópico e cirúrgico (DR = -0,13, IC 95% = -0,17 a -0,09), validando melhores resultados no último grupo. A recorrência foi avaliada em cinco pesquisas (n = 1331) e não houve diferença entre as duas formas de terapêutica (DR = 0,01, IC 95% = -0,00 a 0,02). As taxas de mortalidade foram obtidas de quatro estudos (n = 1107), e não se evidenciou diferença entre os grupos envolvidos (DR = -0,01, IC 95% = -0,02 a 0,00). Conclui-se que as taxas de sobrevida de 3, 5 e 10 anos, recorrência e mortalidade são semelhantes em ambos os grupos. Considerando-se as taxas de complicação, a abordagem endoscópica confere resultados mais apropriados e, analisando-se as taxas de ressecção completa, ela é inferior à cirurgia / Clinical and oncological outcomes of endoscopic resection of early gastric cancer (EGC), considering the indication criteria, compared to surgery, have not been reported in systematic reviews. To address the short- and long-term outcomes of endoscopic resection compared to surgery in the treatment of EGC, a systematic review was performed, establishing the available data to an unpublished 2a strength of evidence, better handling clinical practice. A systematic review and meta-analysis using Medline, Embase, Cochrane, LILACS, Scopus and CINAHL databases were done. Eleven retrospective cohort studies were selected to quantitative and qualitative synthesis. All studies included patients diagnosed with EGC that compared outcomes considering endoscopic treatment and surgery. The included records involved 2654 patients with EGC that filled the standard or expanded indications for endoscopic resection. Different endoscopic treatment modalities were analyzed, mainly mucosal resection procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), compared to surgery. Information of the selected studies was extracted on characteristics of trial participants, inclusion and exclusion criteria, types of interventions and outcomes (different survival rates, adverse events, complete resection, recurrence and mortality rates). The analysis of the absolute risks of the outcomes was performed using the software RevMan, by computing risk differences (RD) of dichotomous variables. Data on RD and 95% confidence interval (CI) for each outcome were calculated using the Mantel-Haenszel test and inconsistency was qualified and reported in X2 and the Higgins method (I2). Sensitivity analysis was performed when heterogeneity was higher than 50%. All pooled analyses were initially based on fixed-effects model. Three-year survival data were available for six studies (n = 1197). There were no RD in 3-year survival data after endoscopic and surgical treatment of EGC (RD = 0.01, 95% CI = -0.02 to 0.05). Five-year survival data (n = 2310) showed no evidence of a difference between the two groups (RD = 0.01, 95% CI = -0.01 to 0.03). The data analysis, in 551 patients, showed no difference in 10-year survival rates between the approaches (RD = -0.02 and 95% CI = -0.15 to 0.10). Complication data were identified in eight studies (n = 2439). A significant difference was detected (RD = -0.08, 95% CI = -0.10 to -0.05), demonstrating better results with endoscopic approach. Complete resection data was analyzed in 536 patients. It showed significant difference in complete resection rates between endoscopic and surgical treatment of EGC (RD = -0.13, 95% CI = -0.17 to -0.09), exhibiting improved results in the surgical group. Recurrence data were analyzed in five studies (n = 1331) and there was no difference between the approaches (RD = 0.01, 95% CI = -0.00 to 0.02). Mortality data were obtained in four studies (n = 1107), and there was no difference between treatment modalities (RD = -0.01, 95% CI = -0.02 to 0.00). This systematic review concludes that 3-, 5- and 10-year survival, recurrence and mortality rates are similar for both groups. Considering procedure-related complication rates, endoscopic approach achieves significantly better results and, analyzing complete resection data, it is considered worse than surgery

No presente estudo, 30 pacientes, do sexo masculino com idade mediana de 29 anos, portadores de hérnias inguinais / inguino-escrotais, unilaterais, indiretas e primárias, sem encarceramento ou estrangulamento, foram submetidos à hernioplastia inguinal, por meio de inguinotomia, sob raqui-anestesia em regime de internação hospitalar. A técnica de correção utilizada foi a de Bassini modificada, sendo que estas modificações repousam no tipo da incisão, abordagem da fáscia transversalis e no reforço da parede posterior do canal inguinal. Os objetivos foram os de avaliar os resultados do pós-operatório mediato quanto aos eventos: intensidade e duração da dor pós-operatória e o tempo de retorno às atividades normais, estabelecendo assim a duração maior ou menor do período de convalescença. Das hérnias operadas 33,33% e 66,67% foram classificadas no intra-operatório como tipos I e II de Nyhus, respectivamente. A duração da cirurgia variou entre 45 e 85 minutos, com média de 66,46 minutos e mediana de 66,5 minutos. A permanência hospitalar foi menor que 24 horas. O índice de mortalidade foi nulo e o seguimento foi feito no 10º e 30° dias de pós-operatório. A intensidade média da dor pós-operatória atingiu seu pico máximo no 1º dia, alcançando 2,93 na escala analógica decimal, sendo que a partir do 5° dia de pós-operatório se tornou insignificante. O retorno às atividades habituais e sociais se deu em um período médio de 5,34 dias. O tempo de retorno ao trabalho alcançou a média de 11,23 dias e mediana de 5 dias. Observou-se complicação leve em dois pacientes (6,67%), que apresentaram edema de bolsa escrotal de rápida resolução. Não se observou complicações infecciosas apesar do não uso de antimicrobianos. A análise dos dados obtidos permite concluir que o procedimento é exeqüível, com boa aceitação por parte dos pacientes, apresentando resultados comparáveis aos obtidos na literatura / In the present study, 30 patients, of the male sex, with an average age of 29, victims of inguinal hernias/ inguino-scrotum, unilateral, indirect and primaries, without confinement or strangulation, were submitted to inguinal hernioplasty, thru inguinotomy, under rachianesthesia on a regimen as hospital in--patients. The correction technique used was the modified- Bassini, since these modifications lie in the kind of incision, approaching of the fascia transversalis and in the reinforcement of the posterior wall of the inguinal duct. The purposes were of evaluating the mediate post-operative results as to the events: intensity and duration of the post-operative pain in the period of time of return to the normal activities, thus determining the longer or shorter duration of the recovery period. Among the operated hernias 33.33% and 66.67% they were classified in the intra-operative as types I and II of Nyhus, respectively. The duration of the surgery varied between 45 and 85 minutes, with an average of 66.46 minutes and median of 66.5 minutes. The in-patients stay in the hospital was less than 24 hours. The mortality rate was null and the follow up was made on the 10th and 30th days of the post operative. The average intensity of the post-operative pain reached its appex on the 1st day, reaching 2.93 in the decimal analogical scale, and as of the 5th day of the post-operative it became insignificant. The return both to the usual and social activities happened in an average period of time of 5.34 days. The period of time of returning to work reached an average of 11.23 days and a median of 5 days. A slight complication was observed in two patients (6.67%), who had edema in the scrotum pouch of fast solution. No infectious complications were detected in spite of not using any anti-microbians. The analysis of the data obtained allow to conclude that the procedure is feasible, with good approval on the part of the patients, presenting results comparable to the ones obtained in the literature