Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.

Keywords: Pleural Mesothelioma; Treatment; Molecular Alterations.

Objective: To evaluate the experience in diagnosing and treating malignant pleural mesothelioma (MPM) accumulated over 5 years in a tertiary public hospital. Methods: The medical charts of the patients diagnosed with MPM between January of 2000 and February of 2005 were evaluated retrospectively. Results: Of the 17 patients analyzed, 14 were male and 3 were female. The mean age was 54.1 years (range, 13-75 years). The biopsy specimens for histopathological examination were obtained through thoracoscopy in 9 patients (53%), Cope needle in 5 (29.5%), and open pleural biopsy in 3 (17.5%). The following histological types were identified: epithelial, in 14 patients (82%); sarcomatoid, in 1 (6%); and biphasic, in 2 (12%). The therapeutic approaches used were as follows: multimodal (pleuropneumonectomy and adjuvant radiotherapy and chemotherapy) in 6 patients (35%); chemotherapy and radiotherapy in 6 (35%); radiotherapy alone in 3 (17.5%); and chemotherapy alone in 2 (12%). The mean survival was 11 months (range, 1-26 months). Conclusions: In the cases studied, an integrated multidisciplinary approach was used, and a highly complex hospital infrastructure was available for the diagnosis and treatment of MPM, as recommended in the literature. However, the mean survival was only 11 months, reflecting the aggressiveness of the disease.

Keywords: Mesothelioma; Pleura; Surgery; Diagnosis.

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

Keywords: Occupational diseases; Mesothelioma; Genes, tumor suppressor; Oncogenes; Signal transduction.

Objective: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). Methods: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. Results: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. Conclusion: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5% immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.

Keywords: Pleural neoplasms; Mesothelioma; Tumor markers, Biological; Carcinoembryonic antigen; Prognosis.

Objective: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. Methods: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. Results: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. Conclusions: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

Keywords: Mesothelioma, malignant/pathology; Mesothelioma, malignant/diagnosis; Immunohistochemistry; Registries.

Objective: To evaluate the safety and feasibility of the use of indwelling pleural catheters (IPCs) in patients with malignant pleural effusion (MPE). Methods: We prospectively collected data from patients with MPE undergoing IPC placement between January of 2014 and July of 2015. All patients submitted to IPC placement had a life expectancy > 30 days, in accordance with the MPE treatment guidelines established by the British Thoracic Society. The data collected included gender, age, body mass index, primary cancer site, duration of IPC drainage, IPC-related complications, length of hospital stay, pleural effusion recurrence, and occurrence of spontaneous pleurodesis. Results: A total of 19 patients underwent IPC placement during the study period. Median overall survival after IPC insertion was 145 days. The median follow-up among the surviving patients was 125 days (range, 53-485 days), and the median time between catheter insertion and removal was 31 days (range, 2-126 days). There were IPC-related complications in 5 patients (26.2%), and spontaneous pleurodesis was achieved in 8 (42.0%). Among those 8 patients, the IPC was removed between days 30 and 126 in 4, and spontaneous pleurodesis occurred within the first 30 days in 4. Conclusions: The use of IPCs seems to be feasible and safe in patients with MPE.

Keywords: Pleural effusion, malignant; Survival; Palliative care.

Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

Keywords: Biopsy; Pleural effusion, malignant/diagnosis; Pleural effusion, malignant/epidemiology.

Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the usefulness of new diagnostic tools, as well as the efficacy of new medications and drug combinations, new diagnostic and treatment algorithms have been developed. Likewise, in order to simplify the clinical management of patients, the classification of pulmonary hypertension has been changed in an attempt to group the various forms of pulmonary hypertension in which the diagnostic and therapeutic approaches are similar. The objective of this review was to discuss these modifications, based on the 2005 Brazilian guidelines for the management of pulmonary hypertension, emphasizing what has been added to the international guidelines.

Keywords: Hypertension, pulmonary/diagnosis; Hypertension, pulmonary/therapy; Clinical protocols.

In view of the tragic fire at a nightclub in the city of Santa Maria, Brazil, which culminated in the sudden death of 232 young people, we decided to review the literature regarding smoke inhalation injury caused by enclosed-space fires, which can be divided into direct thermal damage, carbon monoxide poisoning, and cyanide poisoning. Such injuries often call for immediate orotracheal intubation, either due to acute airway obstruction or due to a reduced level of consciousness. The diagnosis and the severity of the thermal injury can be determined by fiberoptic bronchoscopy. The levels of gases and gas by-products in the bloodstream should be assessed as rapidly as possible, even while still at the scene of the incident. First responders can also treat carbon monoxide poisoning, with immediate administration of oxygen at 100%, as well as cyanide poisoning, with oxygen therapy and hydroxocobalamin injection.

Keywords: Smoke inhalation injury; Carbon monoxide; Cyanides.

For early-stage lung cancer, the treatment of choice is surgery. In patients who are not surgical candidates or are unwilling to undergo surgery, radiotherapy is the principal treatment option. Here, we review stereotactic body radiotherapy, a technique that has produced quite promising results in such patients and should be the treatment of choice, if available. We also present the major indications, technical aspects, results, and special situations related to the technique.

Keywords: Radiation oncology; Lung neoplasms/radiotherapy; Lung neoplasms/surgery; Respiratory function tests.

We summarize here data regarding the spectrum of action, the pharmacological aspects, the toxicological aspects and the clinical efficacy of liposomal amphotericin B, amphotericin B in colloidal dispersion, amphotericin B lipid complex, voriconazole and caspofungin. We discuss the use of these more recently introduced antifungal agents in terms of their safety, efficiency and cost. We also offer suggestions for the clinical use of these drugs in pulmonary and systemic infections, with an emphasis on the lower toxicity of the lipid formulations of amphotericin B in comparison with conventional medications. In addition, we explore the possibility of using voriconazole as the primary treatment for invasive infections such as aspergillosis, as well as those caused by Scedosporium spp. and Fusarium spp., together with that of using caspofungin to treat disseminated candidiasis and invasive aspergillosis.

Keywords: Aspergillosis; Lung diseases, fungal/drug therapy; Amphotericin b/administration & dosage;

Objective: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. Methods: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related to the pleural metastasis. Results: We evaluated 145 patients, 87 (60%) of whom had tested positive for malignant cells in the pleural fluid. Ductal histology was observed in 119 (82%). The triple-negative breast cancer phenotype was seen in 25 cases (17%). Those patients had the worst prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%) died during the follow-up period (through June of 2011). The mean survival after the identification of malignant pleural effusion was 6 months. Conclusions: In patients with triple-negative breast cancer who test positive for malignant cells in the pleural fluid, the prognosis is poor and survival is reduced.

Keywords: Pleural effusion, malignant/mortality; Breast neoplasms/mortality; Breast neoplasms/genetics.

Objective: Talc pleurodesis is a widely used treatment option for malignant pleural effusion (MPE). However, the optimal form of administration remains controversial. Thus, we performed a systematic review and meta-analysis to assess the effectiveness of talc slurry (TS) in comparison with thoracoscopic talc insufflation/poudrage (TTI) for MPE treatment. Methods: We searched PubMed, EMBASE, and Cochrane Library databases for studies that compared TS with TTI in patients with MPE. We used a random-effects model with a 95% CI to pool the data. Heterogeneity was assessed with I² statistics. Results: We included eight studies involving 1,163 patients, 584 of whom (50.21%) underwent TS. Pleurodesis failure rates were similar between the procedures (OR = 1.07; 95% CI: 0.56-2.06; p = 0.83; I² = 62%); and 68% of patients (95% CI: 0.31-1.47; p = 0.33; I² = 58%) had postoperative complications, which were lower in patients in the TS group than in the TTI group. In a subgroup analysis considering only randomized clinical trials, the failure rate was significantly lower in the TS treatment group (OR = 0.62; 95% CI: 0.42-0.90; p = 0.01; I² = 0%). Similarly, dyspnea was less common in the TS group (OR = 0.74; 95% CI: 0.41-1.34; p = 0.32; I² = 55%). Adverse effects were reported in 86 patients, and no significant difference was seen between the TS and TTI groups: empyema (OR = 1.43; 95% CI: 0.36-5.64; p = 0.86; I² = 0%), pain (OR = 1.22 (95% CI: 0.67-2.21; p = 0.51; I² = 38%), and pneumonia (OR = 1.15; 95% CI: 0.30-4.46; p = 0.86; I² = 27%). Conclusions: Our findings suggest that TS is an effective treatment for MPE, with no significant increase in adverse events. Results suggest equivalent efficacy and safety for both procedures.

Keywords: Talc; Pleurodesis; Pleural effusion, malignant.

Objective: To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE). Methods: This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure. Results: Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35 patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in 10 (12%). No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL; interquartile range: −225 to 257 mL; p = 0.923), and clinical success of pleurodesis (85.8%; p = 0.676). Conclusions: Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE.

Keywords: Pleurodesis; Pleural effusion, malignant; Tomography; Catheters.

A 34-year-old patient had had Crohn's disease (CD) for eight years; she was seen for complaints of thoracic pain and fever, without gastrointestinal manifestations. Initial laboratory exams were compatible with the presence of inflammatory activity (VHS = 45 mm for normal value of 20 mm and PCR+). The physical exam revealed signs of pleural effusion in the left hemithorax base, which was confirmed by thoracic RX. The pleural liquid analysis showed that the cells were 100% of lymphocytes, with negative BAAR research. The pleural biopsy evidenced non caseous granuloma. Despite the tuberculosis treatment, the patient only got better when corticotherapy was introduced in high doses, suggesting the activity of CD as the cause of the pleural effusion. This case establishes a connection between activity of CD and manifestations of lung disease.