Typical Lung Carcinoids with Metastasis: Potential Role of MicroRNAs in the Regulation of Adaptive Immunity Associated with Disease: a Case Study.

BACKGROUND/AIMS: Lung carcinoids are uncommon neuroendocrine tumours. Molecular features of lung carcinoids have been poorly defined. microRNAs (miRNAs) are potent gene expression regulators with important roles in cancer development and progression. However, little is known on the role of miRNAs in the pathogenesis of lung carcinoids. Our goals were to identify commonly deregulated miRNAs in a rare case of lung carcinoid of typical histology with metastasis, as well as map miRNA target genes in pathways potentially associated with disease development and progression. METHODS: miRNA expression profiles were assessed using the TaqMan Low Density Arrays, which is a platform including 384 miRNAs. miRNA profiles were generated in the tumor and its corresponding lymph node metastasis, compared to reference normal lung tissues. Furthermore, miRNA expression was validated in a separate, publicly available external dataset (n=19 typical lung carcinoids; 2/19 were metastatic tumors, compared to six normal lung tissues, GSE77380). Following this analysis, computational tools were applied for data interpretation. miRTarBase was used to determine miRNA-target genes, followed by ToppGene Suite analysis to identify pathways and biological functions. In addition, the expression of genes targeted by miRNAs was validated in a second, separate external dataset (n=13 tumour samples, GSE35679). GEO2R data analysis tool was used in both validation analyses (miRNAs and genes). RESULTS: We identified 15 commonly significantly downregulated miRNAs (fold change, FC≥2 and p<0.05) in the tumour and its paired metastasis, with further decreasing levels in the metastatic lesion. Downregulation of miR-126-3p and miR-146b-5p was validated in the external dataset GSE77380. In addition, SOX2 and TCF4 genes, targeted by miR-126-3p, were consistently overexpressed in a subset of six typical lung carcinoids from the external dataset GSE35679. Pathways analysis showed that miRNAs miR-126-3p and miR-146b-5p target genes with a role in the regulation of adaptive immune response. CONCLUSION: Our results contribute to the identification of miRNA expression changes in a typical lung carcinoid and its corresponding lymph node metastasis. Down-regulated levels of miR-126-3p and miR-146b-5p and target gene over-expression could play a role in the progression of this case of primary typical lung carcinoid to regional metastasis. Identified miRNAs and target genes are potential candidates for validation in a larger number of cases.

Deregulated microRNAs Are Associated with Patient Survival and Predicted to Target Genes That Modulate Lung Cancer Signaling Pathways.

(1) Background: Although the advances in diagnostic and treatment strategies, lung cancer remains the leading cause of cancer-related deaths, worldwide, with survival rates as low as 16% in developed countries. Low survival rates are mainly due to late diagnosis and the lack of effective treatment. Therefore, the identification of novel, clinically useful biomarkers is still needed for patients with advanced disease stage and poor survival. Micro(mi)RNAs are non-coding RNAs and potent regulators of gene expression with a possible role as diagnostic, prognostic and predictive biomarkers in cancer. (2) Methods: We applied global miRNA expression profiling analysis using TaqMan® arrays in paired tumor and normal lung tissues (n = 38) from treatment-naïve patients with lung adenocarcinoma (AD; n = 23) and lung squamous cell carcinoma (SCC; n = 15). miRNA target genes were validated using The Cancer Genome Atlas (TCGA) lung AD (n = 561) and lung SCC (n = 523) RNA-Seq datasets. (3) Results: We identified 33 significantly deregulated miRNAs (fold change, FC ≥ 2.0 and p < 0.05) in tumors relative to normal lung tissues, regardless of tumor histology. Enrichment analysis confirmed that genes targeted by the 33 miRNAs are aberrantly expressed in lung AD and SCC, and modulate known pathways in lung cancer. Additionally, high expression of miR-25-3p was significantly associated (p < 0.05) with poor patient survival, when considering both tumor histologies. (4) Conclusions: miR-25-3p may be a potential prognostic biomarker in non-small cell lung cancer. Genes targeted by miRNAs regulate EGFR and TGFß signaling, among other known pathways relevant to lung tumorigenesis.

Intra-Operative Mitomycin-C as Adjuvant Therapy in External and Endonasal Dacryocystorhinostomy: Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effect of mitomycin-C (MMC) on the success of external (Ex-DCR) or endoscopic dacryocystorhinostomy (En-DCR). METHOD: A systematic review of randomized clinical trials of Ex- or En-DCR with and without the use of MMC to treat primary acquired nasolacrimal duct obstruction (NLDO) was done. Two authors independently searched six databases from 1990 to 2019, using the terms "dacryocystorhinostomy" and "mitomycin-C." Statistical and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-seven studies involving 2158 surgeries were included in this systematic review. The Ex-DCR group comprised 14 studies [odds ratio (OR): 2.74; 95% confidence intervals (CI) 1.54-4.87; I2 = 30%], while the En-DCR group 13 studies (OR: 1.69; 95% CI 1.21-2.37; I2 = 0%). The use of MMC slightly increased the success rate of Ex- or En-DCR (OR: 2.1; 95% CI 1.52-2.9; I2 = 14%). CONCLUSION: The intraoperative use of MMC is safe and slightly improves the success rate of Ex- or En-DCR. However, the evidence was very weak.

Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis

Abstract Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time ≥ one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I2 = 17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I2 = 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I2 = 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I2 = 79.8%). Conclusions The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.

Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.

Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time ≥ one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I 2 = 17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I 2 = 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I 2 = 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I 2 = 79.8%). Conclusions The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.

New sternal closure methods versus the standard closure method: systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate, by means of a systematic review, the efficiency of new methods for sternal closure in order to prevent sternal wound complications after sternotomy. METHODS: The method of study was a systematic review of randomized clinical trials. We included studies that used rigid plates, thermoreactive clips, cables and flat wires, in comparison with the standard closure method. Patients included adults, regardless of gender and race. RESULTS: Seven clinical trials were included involving 1810 patients. Five trials were carried out in the USA, 1 in Australia and 1 in Italy, and the trials include both male and female patients. The included studies compared conventional sternal closure with new closure methods (rigid plate, thermoreactive clips, cables and flat wires). The new sternal closure methods make little or no difference compared to the standard closure when we analyse deep sternal wound infection [risk ratio 0.38, 95% confidence interval (CI) 0.02-7.63; I2 = 74%; 5 studies], superficial wound infection (risk ratio 1.34, 95% CI 0.46-3.92; I2 = 11%, 3 studies) and death (risk ratio 1.16, 95% CI 0.42-3.21; I2 = 0%, 3 studies), but pain score was lower in new sternal closure methods (mean difference -0.57, 95% CI -0.98 to -0.16, I2 = 0%, 3 studies). There were no meta-analyses of sternal union, hospital stay, reoperation or mechanic ventilation time because of the high heterogeneity between the studies in terms of these outcomes. CONCLUSIONS: New sternal closure methods probably make little or no difference regarding the prevention of sternal complications in the postoperative period when compared to the standard closure method.

Thymectomy in nonthymomatous myasthenia gravis - systematic review and meta-analysis.

BACKGROUND: The objective of this study is to evaluate by means of a systematic review, the efficacy of thymectomy as compared to medical treatment for non-thymomatous myasthenia gravis (MG). METHODS: Medline, Embase, and Lilacs were searched for experimental and observational studies that compared non-surgical (drug therapy) and surgical treatment of non-thymomatous MG (thymectomy performed by the transsternal approach). Inclusion criteria were: studies that compared the two types of treatment and had at least 10 adult patients in each group. Exclusion criteria were articles published before 1970, as well as those that included patients treated before 1950. The outcomes evaluated were: remission, and improvement rates. RevMan 5.3 software provided by the Cochrane Collaboration was used. When the heterogeneity between the studies was greater than 75%, a meta-analysis was not performed according to RevMan guidelines. RESULTS: The total number of patients evaluated in 19 articles selected was 5841 (2911 surgical and 2930 non-surgical). Two included randomized clinical trials showed superiority of the surgical treatment over the non-surgical. Four retrospective studies with 379 patients paired by gender, age, and other confounders, also showed superiority of surgical treatment (OR 4.10, 95% CI 2.25 to 7.44; I2 = 20%). In meta-analyses, remission assessed in 17 studies (5686 patients) was greater in patients who underwent surgical treatment (OR 2.34, 95% CI 1.79 to 3.05; I2 = 56%). For improvement assessed in 13 studies (3063 patients) were not appropriate to carry out the meta-analysis due to the high heterogeneity among the studies in the outcome (87%). CONCLUSION: Thymectomy may be considered effective in the treatment for non-thymomatous MG, with remission rate higher than for non-surgical treatment.

Palliative care for terminally ill patients in the intensive care unit: Systematic review and metaanalysis.

OBJECTIVE: The purpose of our systematic review was to determine whether the introduction of palliative care (PC) teams reduces length of stay and/or mortality for terminally ill patients (TIPs) in an intensive care unit (ICU). METHOD: We hoped to examine studies that compared TIPs in an ICU who received end-of-life care following implementation of a PC team (intervention group) to those who received care where PC teams had not yet been introduced (control group). We searched MEDLINE via PubMed, LILACS, Scopus, Embase, and Cochrane CENTRAL (search conducted in December of 2015) without language restrictions. Our outcome measures were length of stay in an ICU, presented as an average difference with a corresponding 95% confidence interval (CI 95%), and mortality in the ICU, presented as a risk ratio with a corresponding CI 95%. Two of our authors independently extracted all of the data. RESULTS: Of the 399 publications identified, 27 were selected for full-text analysis and 19 were excluded, leaving 8 articles for inclusion, which involved a total of 7,846 patients. A metaanalysis of mortality in the ICU was conducted with four studies. Lower mortality was found in the intervention group: risk ratio = 0.78 (CI 95% = 0.70-0.87), p < 0.00001, I 2 = 18%. Length of stay in the ICU was presented as a mean and standard deviation in four studies, and the result was a reduction of ~2.5 days in the length of stay with application of the intervention: mean = -2.44 days (CI 95% = -4.41 to -0.48), p = 0.01, I 2 = 86%. SIGNIFICANCE OF RESULTS: Introduction of palliative care teams can reduce mortality rates in the ICU, and perhaps shorten length of stay in the ICU for terminally ill patients.

Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.

Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

Persistent pleuropulmonary air leak treated with autologous blood: results from a university hospital and review of literature.

BACKGROUND: Persistent air leak after pulmonary resection is a difficult complication for thoracic surgeons to manage. OBJECTIVES: To show the results of our experience treating persistent pleuropulmonary air leak with autologous blood and review the literature on this specific method of treatment. METHODS: Retrospective study of patients with persistent aerial pleuropulmonary fistula treated with autologous blood. The patient's own blood was collected from a peripheral vein and directly introduced through the pleural drain. An inverted siphon was located in the drainage system to avoid prolonged clamping of the drain. This siphon impeded blood return but not air escape. RESULTS: Between January 2001 and August 2008, 27 patients were treated by the above method. Patient age ranged from 2 to 74 years, and 78% were male. Each procedure used a mean quantity of 92 ml blood. Mean persistent air leak time before pleurodesis was 10.6 days and mean time to fistula resolution after pleurodesis was 1.5 days. Twenty-three (85%) patients had persistent pleuropulmonary air leak closed with the above procedure. CONCLUSION: Treating persistent pleuropulmonary air leak with autologous blood is promising, but further studies are required to quantify its real effectiveness.

Sindrome da veia cava superior: avaliacao cintilografica pre e pos radioterapia. Relato de caso / Superior vena cava syndrome: scintilographic evaluation pre and pos radiotherapy. A case report

Relatamos um caso de sindrome da veia cava superior,em paciente de 68 anos, devido a carcinoma epidermoide em lobo superior do pulmao direito. O paciente apresentava importante circulacao colateral bilateralmente. A venografia radionuclidica e a cintilografia pulmonar com glucoheptonato realizadas apos a radioterapia mostraram, de forma nao invasiva, diminuicao da circulacao colateral e da captacao pela massa tumoral.

Funçäo pulmonar na evoluçäo de 35 doentes com paracoccidioidomicose / Pulmonary function in the course of 35 patients with paracoccidioidomycosis

Lesöes pulmonares observadas na paracoccidioidomicose (pbmicose) pela radiologia foram designadas: leve, moderada e grave de acordo com critério estabelecido pelos autores. Lesöes infiltrativas intersticiais bilaterais núdulo fibrolineares e cotonosas foram identificadas respectivamente em 34 e em 23 doentes. Formas leve, moderada e grave assinaladas respectivamente em 6, 10 e 19 mostraram à análise radiológica evolutiva melhora em 2, piora em 15 e manutençäo do padräo da lesäo em 18 doentes. Testes de funçäo pulmonar realizados nos doentes durante o retorno ambulatorial evidenciaram: 12 com padräo espirográfico normal, 20 obstrutivos e 3 mistos; 34 doentes estavam hiperventilando e todos apresentaram aumento da diferença alveólo arterial. Os resultados obtidos permitiram supor que a fibrose residual descrita nos padröes radiológicos; manutençäo e piora de 33 deles aliada à doença obstrutiva crônica verificada pelas provas de funçäo pulmonar constituíram subsídios para o desenvolvimento do Cor pulmonale assinalado

Paracoccidioidomicose pulmonar agressiva, endotraqueíte estenosante e cor-pulmonale subagudo: descriçäo de um caso / Aggressive pulmonary paracoccidioidomycosis, stenosing endotracheitis and cor pulmonale: report of a case

A paracoccidioidomicose (Pbmicose) atinge os pulmöes pela via inalatória, onde se estabelece o complexo primário semelhante ao da tuberculose. A traquéia comprometida pela via tubohemolinfática desenvolveria reaçäo inflamatória em processo granulomatoso levando à obstruçäo estenosante com asfixia. Acompanhou-se um doente, masculino, 32 anos, branco, natural de Sarutaiá (SP), lavrador, que há 8 meses desenvolveu tosse expectorativa branco-amarelada, diária, sem fatores de melhora ou piora e dispnéia inicial discreta. Há 4 meses, anorexia, fraqueza e astenia. Há 1 mês a dispneia se agravou. Perdeu 15 kg. Tabagista e etilista há 16 anos. Exame físico revelou: PA - 10/7 mmHg, FR = 28 bpm, peso 31 kg, hipocratismo digital e hipotrofia muscular Tórax enfisematoso e síndrome obstrutivo aos testes de funçäo pulmonar. Coraçäo: P2 desdobrada e hiperfonética. Hepatesplenomegalia. Desenvolveu cor-pulmonale e insuficiência adrenal à internaçäo, evoluindo após 45 dias para óbito em insuficiência respiratória aguda asfixiante, apesar da terapia antifúngica ter sido completa. A literatura médica revista näo mostrou registro de caso semelhante de cor-pulmonale e insuficiência adrenal de evoluçäo subaguda

Bagaçose: relato de um caso / Bagassosis: a case report

Apresenta-se o primeiro caso brasileiro de bagaçose, histologicamente documentado. A imunofluorescência direta da biopsia pulmonar revelou ausência de complexos antígeno-anticorpo. Acredita-se que a patogenia da doença é devida a reaçäo de hipersensibilidade retardada a antígenos de bolores presentes nas fibras do bagaço aspirado