Proteomics on malignant pleural effusions reveals ERα loss in metastatic breast cancer associates with SGK1-NDRG1 deregulation.

Breast cancer (BCa) is a highly heterogeneous disease, with hormone receptor status being a key factor in patient prognostication and treatment decision-making. The majority of primary tumours are positive for oestrogen receptor alpha (ERα), which plays a key role in tumorigenesis and disease progression, and represents the major target for treatment of BCa. However, around one-third of patients with ERα-positive BCa relapse and progress into the metastatic stage, with 20% of metastatic cases characterised by loss of ERα expression after endocrine treatment, known as ERα-conversion. It remains unclear whether ERα-converted cancers are biologically similar to bona fide ERα-negative disease and which signalling cascades compensate for ERα loss and drive tumour progression. To better understand the biological changes that occur in metastatic BCa upon ERα loss, we performed (phospho)proteomics analysis of 47 malignant pleural effusions derived from 37 BCa patients, comparing ERα-positive, ERα-converted and ERα-negative cases. Our data revealed that the loss of ERα-dependency in this metastatic site leads to only a partial switch to an ERα-negative molecular phenotype, with preservation of a luminal-like proteomic landscape. Furthermore, we found evidence for decreased activity of several key kinases, including serum/glucocorticoid regulated kinase 1 (SGK1), in ERα-converted metastases. Loss of SGK1 substrate phosphorylation may compensate for the loss of ERα-dependency in advanced disease and exposes a potential therapeutic vulnerability that may be exploited in treating these patients.

Outcomes of Airway Stents in the Palliative Care of Patients With Cancer.

INTRODUCTION: A significant proportion of patients with advanced primary or metastatic intrathoracic malignancy will eventually develop central airway obstruction. The morbidity associated with malignant airway obstruction (MAO) is considerable and the management is difficult. Our aim was to evaluate the outcomes of tracheobronchial stenting in patients with MAO and its role in palliative care. MATERIAL AND METHODS: This retrospective study involved a consecutive case series of patients with advanced cancer with MAO who underwent tracheobronchial stenting between August 2014 and August 2019. The European Cooperative Oncology Group (ECOG) scale was used to evaluate patient functional status before and after tracheobronchial stenting. Univariate survival analysis included Kaplan-Meier curves with Log-Rank test, while Cox regression was used as a multivariate analysis. RESULTS: We included 28 patients with median age of 55.0 years (interquartile range = 49.3-66.5) and 89.3% male. The most frequent primary tumour was the esophagus followed by lungs. The majority of the patients (75%) expressed immediate symptom relief after stenting and there was a significant improvement in the mean ECOG performance status (PS; P = .005). There was no intraprocedure mortality and complications were observed in 6 patients. The median survival after airway stenting was 39.0 days (95% CI = 32.2-45.8) with poorer PS after stent insertion associated with lower overall survival (hazard ratio = 2.3 [95% CI = 1.1-4.9], P = .030) on multivariate analysis. CONCLUSION: Airway stent is a safe and effective procedure that offers rapid palliation of symptoms with no major complications. Therefore, stent placement should be considered as part of the treatment of patients with terminal cancer.

Predictors of survival and technical success of bronchoscopic interventions in malignant airway obstruction.

BACKGROUND: Malignant airway obstruction (MAO) leads to quality of life impairment and increased mortality. Interventional bronchoscopy allows airway patency restoring, leading to a better survival. We investigated predictors of survival and successful bronchoscopic intervention among MAO patients. METHODS: This observational prospective study enrolled 100 patients who were newly diagnosed with MAO. Survival was estimated with Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses were performed using Cox proportional hazard models. Univariate and multivariate logistic regression were used for odds ratio calculation. RESULTS: A proportion of 73% of the patients were male with a median age was 62.5 years (range, 21-88 years). Lung cancer was the most common primary malignancy (74%). The majority had single (61%), endoluminal (62%) lesions and were classified as grade III in Myer Cotton scale (57%). The most used techniques comprised mechanical debulking (n=81) and laser therapy (n=68). Twenty-two airway stents were placed. While eleven patients were considered untreatable, technical success was achieved in 78%. Haemorrhage was the most common acute complication (16%). No deaths occurred as a result of the procedure. Median global survival was 8 months. Adjusting for age and Eastern Cooperative Oncology Group Performance Status (ECOG), extrinsic compression or mixed airway obstructions [hazard ratio (HR) =2.075; P=0.012], successful bronchoscopic intervention (HR =0.468; P=0.025) and initiation of cancer treatment (HR =0.373; P=0.006) were independent predictors of survival. The absence of distal airway patency on thoracic CT was independently associated with failure of the intervention [odds ratio (OR) =0.013; P<0.001]. CONCLUSIONS: Interventional bronchoscopy has proven to be an efficient and safe strategy to manage MAO patients. The patients who benefit the most in terms of survival are those with purely endoluminal lesions, in whom technical success was achieved and those whose cancer-specific treatment was initiated. Distal airway patency on thoracic CT predicts the technical success of bronchoscopic intervention.

Invasive pulmonary aspergillosis in a patient with seminomatous testicular cancer.

In the past years there has been an increasing incidence of invasive fungal infections, particularly in immunocompromised patients. These infections continue to pose a diagnostic and therapeutic challenge. Considering these facts, the authors report a clinical case of invasive pulmonary aspergillosis which illustrates the improved outcomes associated with the extended-spectrum triazole, voriconazole, used in first-line therapy.

Primary tracheobronchial amyloidosis--two case reports.

Primary tracheobronchial amyloidosis is a form of respiratory amyloidosis, characterised by insoluble amyloid fibril proteins deposits along the airways wall. It is an uncommon disease, requiring a tissue sample to establish the definite diagnosis based on specific pathological features. The authors report two cases of tracheobronchial amyloidosis, describing their symptoms and the diagnostic and therapeutic procedures that were performed.

Epithelioid hemangioendothelioma - a rare pulmonary tumor.

The authors report a case of a rare pulmonary neoplasm - epithelioid hemangioendothelioma, in a 39 year-old woman, asymptomatic until December 2003, when she developed pleuritic and right-sided chest pain. The patient presented a previous chest radiograph, performed 13 years before, which showed multiple small bilateral pulmonary nodules attributed to tuberculous sequelae. The definitive histological diagnosis was made by lung biopsy through thoracotomy. The patient developed a clinical and imagiological worsening and then therapy with interferon alpha-2a was started. Even with imagiological stability of pulmonary lesions the patient remained symptomatic and died nine months after the diagnosis had been established. The authors emphasise the rarity of this type of pulmonary neoplasm and discuss its clinical presentation, histological features, treatment and prognosis.

Smoking habits and awareness of smoking risks depending on academic background in university students.

OBJECTIVE: To evaluate smoking habits among a group of medical students and engineering students in order to assess whether, depending on their specific academic background, differences in smoking habits and attitudes towards smoking were present. METHODS: Medical and engineering students from the Oporto University were surveyed using a questionnaire, in which they were asked to mention their smoking habits, their perception about cigarette dependence and to point out, from a list of 12 tobacco-related diseases, which were associated with tobacco use.

[Primary cysts and tumors of the mediastinum]. / Cistos e tumores primários do mediastino.

OBJECTIVE: To assess results in patients with primary cysts and tumours of the mediastinum who under- went surgery. METHODS: A retrospective single-centre study was undertaken into patients with primary cysts and tumours of the mediastinum who underwent surgery between January 1992 and December 2004. We analysed demographic data, clinical presentation, type of surgery carried out and procedure, lesion location and histological diagnosis. Predictive malignancy factors were also evaluated. Postoperative morbidity and mortality were noted, as was medium-term results. RESULTS: 171 patients underwent surgery over a 13-year period; 73 female (43%) and 98 male (57%). Mean age was 40.3+/-19.7 years (20 days-78 years). A primary cystic lesion was present in 15 patients (9%). The pri- mary tumours included thymic neoplasms (31%), lymphoma (22%), neurogenic tumours (16%), germ cell tumours (9%) and a miscellaneous group (13%). Malignant neoplasms were present in 78 patients (46%). The antero-superior mediastinum was the most commonly involved site to have a primary cyst or tumour (58%), followed by the posterior mediastinum (24%) and the middle mediastinum (18%). Symptoms were present in 68% of the patients and included chest pain (20%), fever and chills (13%), myasthenia gravis (11%), cough (10%), dyspnoea (10%), and superior vena caval syndrome (7%). Univariate analysis identified symptoms as a predictive factors of malignancy (p<0.001). Types of surgery carried out included postero-lateral thoracotomy (64 patients), median sternotomy (51 patients), anterior mediastinostomy (27 patients), antero-lateral thoracotomy (18 patients), video-assisted thoracic surgery (9 patients) and mediastinoscopy (2 patients). Total excision was performed in 116 patients, enlarged resection in 8 patients, subtotal re- section in 7 patients and biopsy in 40 patients. There was one postoperative death (0.6%). Follow-up was available in 165 patients (96.5%) and ranged from 34 days to 13.4 years (mean 5.7+/-4.0 years). Complementary treatment with chemo and/or radiotherapy was provided in 75 patients. Six patients had to be reoperated on for local recurrence (3) or metastasis (3) of the primary lesion. Fifteen patients died of their disease during the follow-up period. Actuarial survival at five years was 97.6% for benign lesions and 76.4% for malignant tumours. CONCLUSION: Results support surgical resection for benign lesions and an aggressive multimodal approach for malignant tumours.

[Tuberculosis in hospital department health care workers]. / Tuberculose em profissionais de saúde de um serviço hospitalar.

INTRODUCTION: Tuberculosis (TB) is considered an occupational disease in health care workers (HCW) and its transmission in health care facilities is an important concern. Some hospital departments are at higher risk of infection. OBJECTIVE: To describe TB cases detected after TB screening in HCW from a hospital department (Ear, Nose and Throat - ENT) who had had contact with active TB cases. MATERIAL AND METHODS: All HCW (73) from Hospital São João's ENT Unit who had been in contact with two in-patients with active TB underwent TB screening. Those who had symptoms underwent chest X-ray and mycobacteriological sputum exam. RESULTS: Of 73 HCW who underwent TB screening, TB diagnosis was established in 9 (8 female; median age: 30 years; 1 doctor, 6 nurses, 2 nursing auxiliaries). Pulmonary TB was found in 8 and extra- -pulmonary TB in 1. Microbiology diagnosis was obtained in 7 cases by sputum smear, n=2; culture exam in bronchial lavage, n=4 and histological exam of pleural tissue, n=1. In 4 cases, Mycobacterium tuberculosis genomic DNA was extracted from cultures and molecular typing was done. All cases had identical MIRU types, which allowed identification of the epidemiological link. CONCLUSION: Nosocomial TB is prominent and efforts should be made to implement successful infection control measures in health care facilities and an effective TB screening program in HCW. Molecular typing of Mycobacterium tuberculosis facilitates cluster identification.

Mediastinal cystic lymphangioma.

Mediastinal lymphangioma is a rare vascular neoplasm, accounting for 0.7 to 4.5% of all the mediastinum tumors. It is a benign tumor, generally occur- ring as a mediastinal mass of slow growth. Most patients are asymptomatic, being incidentally diagnosed after a routine chest radiograph. The best treatment consists of complete surgical resection. Prognosis depends on the degree of resectability, and recurrence is not expected if the lesion is totally removed.