Malignant Pleural Effusion and Its Current Management: A Review.

Malignant pleural effusion (MPE) is an exudative effusion with malignant cells. MPE is a common symptom and accompanying manifestation of metastatic disease. It affects up to 15% of all patients with cancer and is the most common in lung, breast cancer, lymphoma, gynecological malignancies and malignant mesothelioma. In the last year, many studies were performed focusing on the pathophysiological mechanisms of MPE. With the advancement in molecular techniques, the importance of tumor-host cell interactions is becoming more apparent. Additionally, the process of pathogenesis is greatly affected by activating mutations of EGFR, KRAS, PIK3CA, BRAF, MET, EML4/ALK and RET, which correlate with an increased incidence of MPE. Considering all these changes, the authors aim to present a literature review of the newest findings, review of the guidelines and pathophysiological novelties in this field. Review of the just recently, after seven years published, practice guidelines, as well as analysis of more than 70 articles from the Pubmed, Medline databases that were almost exclusively published in indexed journals in the last few years, have relevance and contribute to the better understanding of the presented topic. MPE still presents a severe medical condition in patients with advanced malignancy. Recent findings in the field of pathophysiological mechanisms of MPE emphasize the role of molecular factors and mutations in the dynamics of the disease and its prognosis. Treatment guidelines offer a patient-centric approach with the use of new scoring systems, an out of hospital approach and ultrasound. The current guidelines address multiple areas of interest bring novelties in the form of validated prediction tools and can, based on evidence, improve patient outcomes. However, the role of biomarkers in a clinical setting, possible new treatment modalities and certain specific situations still present a challenge for new research.

Release of growth factors after mechanical and chemical pleurodesis for treatment of malignant pleural effusion: a randomized control study.

BACKGROUND: Growth factors are key inducers of fibrosis but can also mediate inflammatory responses resulting in increasing pleural effusion and acute respiratory distress syndrome. The primary aim of the study was to analyse growth factors release after performing chemical and mechanical pleurodesis in the first 48 hours at the patients with malignant pleural effusion. The secondary endpoints were to evaluate the effectiveness of the both pleurodeses, symptoms release and the quality of life of patients after the treatment. PATIENTS AND METHODS: A prospective randomized study included 36 consecutive female patients with breast carcinoma and malignant pleural effusion in an intention-to-treat analysis. We treated 18 patients by means of thoracoscopic mechanical pleurodesis and 18 patients by chemical pleurodesis with talcum applied over a chest tube. We gathered the pleural fluid and serum samples in the following 48 hours under a dedicated protocol and tested them for growth factors levels. A quality of life and visual analogue pain score surveys were also performed. RESULTS: Median measured serum vascular endothelial growth factor (VEGF) level after chemical pleurodesis was 930.68 pg/ml (95% CI: 388.22-4656.65) and after mechanical pleurodesis 808.54 pg/ml. (95% CI: 463.20-1235.13) (p = 0.103). Median pleural levels of transforming growth factor (TGF) ß1 were higher after performing mechanical pleurodesis (4814.00 pg/ml [95% CI: 2726.51-7292.94]) when compared to those after performing chemical pleurodesis (1976.50 pg/ml [95% CI: 1659.82-5136.26]) (p = 0.078). We observed similar results for fibroblast growth factor (FGF) ß; the serum level was higher after mechanical pleurodesis (30.45 pg/ml [95% CI: 20.40-59.42]), compared to those after chemical pleurodesis (13.39 pg/ml [95% CI: 5.04 - 74.60]) (p = 0.076). Mechanical pleurodesis was equally effective as chemical pleurodesis in terms of hospital stay, pleural effusion re-accumulation, requiring of additional thoracentesis, median overall survival, but, it shortened the mean thoracic drainage duration (p = 0.030) and resulted in a higher symptoms release and in a better quality of life (p = 0.047). CONCLUSIONS: We recorded an increase in serum VEGF levels after chemical pleurodesis, however on the contrary, an increase in the pleural fluid level of TGFß1 and FGFß] after mechanical pleurodesis with respect to compared group. Although the differences did not reach statistical significance, VEGF, TGFß1 and FGFß remain the most interesting parameters for future research. Considering the mechanisms of growth factors action, we conclude that in our study group mechanical pleurodesis might be more efficient in terms of growth factors release, thoracic drainage duration and resulted in a higher symptoms release and in a better quality of life than chemical pleurodesis.

Giant solitary fibrous tumour of the pleura. Case report and review of the literature.

BACKGROUND: Solitary fibrous tumours of the pleura (SFTP) are rare tumours. They are mostly benign. Only around 12% of them are malign ant. In the initial stage they are mostly asymptomatic and by growing they cause chest pain, irritating cough and dyspnoea on account of the pressure created on the surrounding structures. Rare giant tumours have compression symptoms on the mediastinal structures. The condition requires tiered diagnostic radiology. Preoperative biopsy is not successful in most cases. The therapy of choice is radical surgical tumour removal. Malignant or non-radically removed benign solitary fibrous tumours of the pleura additionally require neoadjuvant therapy. CASE REPORT: A 68-year old patient was hospitalized for giant solitary fibrous tumour of the pleura in the right pleural cavity. With its expansive growth the tumour caused the shift of the mediastinum by compressing the lower vena cava, right cardiac auricle as well as the intermediate and lower lobe bronchus. Due to cardiac inflow obstruction and right lung collapse, the patient's life was endangered with signs of cardio-respiratory failure. After preoperative diagnostic radiology, the tumour was surgically removed. Postoperatively, the patient's condition improved. No disease recurrence was diagnosed after a year. CONCLUSIONS: Giant solitary fibrous tumour of the pleura may cause serious and life-threatening conditions by causing compression of the pleural cavity with its expansive growth. Early diagnosis of the condition enables less aggressive as well as video-assisted thoracic surgery in patients with significantly better state of health. Large tumour surgeries in cardio-respiratory affected patients are highly risk-associated procedures.

Toxicity of magnetic chitosan micro and nanoparticles as carriers for biologically active substances.

Nanoparticles of inorganic magnetic core surrounded by layers of functional coatings are potential representatives of nanostructures for immobilization of bio-substances. Magnetic nanoparticles (MNPs) are often bound in aggregates due to a strong magnetic dipole, which has a lot of advantages, such as large surface area for binding biologically active substances. Chitosan is a polysaccharide polymer that is non-toxic, hydrophilic, biocompatible and has hydroxy and amino groups in its structure. Because of these chemical and biological properties it is a desirable bio-product for immobilization of enzymes and for binding of other biologically active substances. Magnetic micro and nanoparticles were synthesized with chitosan by three different methods; microemulsion process, suspension cross-linking technique and covalent binding of chitosan. Toxic effect of the prepared magnetic particles was determined as well and was examined on five different bacterial cultures; Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and Klebsiella pneumoniae. At concentrations of 10-30 mg of magnetic particles per 0.5 McFarland Standard solution of E. coli and per 400 CFU of S. aureus, P. aeruginosa, E. faecalis in K. pneumonia, no inhibition on the chosen bacterial cultures was detected.

Thoracobiliary fistulas: literature review and a case report of fistula closure with omentum majus.

BACKGROUND: Thoracobiliary fistulas are pathological communications between the biliary tract and the bronchial tree (bronchobiliary fistulas) or the biliary tract and the pleural space (pleurobiliary fistulas). REVIEW OF THE LITERATURE: We have reviewed aetiology, pathogenesis, predilection formation points, the clinical picture, diagnostic possibilities, and therapeutic options for thoracobiliary fistulas. CASE REPORT: A patient with an iatrogenic bronchobiliary fistula which developed after radiofrequency ablation of a colorectal carcinoma metastasis of the liver is present. We also describe the closure of the bronchobiliary fistula with the greater omentum as a possible manner of fistula closure, which was not reported previously according to the knowledge of the authors. CONCLUSIONS: Newer papers report of successful non-surgical therapy, although the bulk of the literature advocates surgical therapy. Fistula closure with the greater omentum is a possible method of the thoracobiliary fistula treatment.

Increased risk of knee injuries and osteoarthritis in the non-dominant leg of former professional football players.

The aim of the study was to evaluate differences in knee injuries and osteoarthritis between the dominant and non-dominant legs of former professional football players. The study cohort comprised 40 retired professional players with an average age of 49.2 years. Participants completed a questionnaire about their sports and personal history with special emphasis on knee injuries/operations of the dominant and non-dominant leg. Bilateral standing knee radiographs were taken. Overall, 29 footballers (73%) had experienced at least one moderate or severe knee injury and 18 (40%) had undergone at least one knee operation during their career. Among those injured, 14 (35%) players had suffered a dominant knee injury and 22 (55%) a non-dominant knee injury. Evidence of osteoarthritis (Kellgren-Lawrence scale > or = 2) was found in 17 (43%) dominant and 23 (58%) non-dominant knees. Professional football players have a significant risk of knee injuries and early osteoarthritis with preponderance in the non-dominant leg.

The effect of platelet-derived growth factors on knee stability after anterior cruciate ligament reconstruction: a prospective randomized clinical study.

BACKGROUND: Arthroscopic reconstruction is a standard surgical procedure in cases of symptomatic knee instability due to rupture of the anterior cruciate ligament. Bone-tendon-bone and hamstring tendon grafts are both in use for anterior cruciate ligament reconstruction. There are no significant differences between the two types of graft in relation to function scores, but there is a difference in anteroposterior stability when measured on the KT-2000 arthrometer: knee joints after reconstruction with bone-tendon-bone autografts are more stable than those reconstructed with hamstring tendon autografts. PURPOSE: To improve knee stability after anterior cruciate ligament reconstruction with a hamstring graft and use of platelet-derived growth factors. BASIC PROCEDURE: Platelet-leukocyte gel was produced from platelet-leukocyte-rich plasma prepared from a unit of whole blood in an autologous platelet separator. The gel was applied locally, after hamstring graft placement. Fifty patients were included in the study: 25 in the platelet gel group, 25 in a control group. We evaluated anteroposterior knee stability with the KT-2000 arthrometer before surgery and at 3 and 6 months after surgery. MAIN FINDINGS: Patients treated with the gel demonstrated significantly better anteroposterior knee stability than patients in the control group. The calculated improvements in knee stability at 6 months were 1.3 +/- 1.8 mm in the control group and 3.1 +/- 2.5 mm in the platelet gel group (P = 0.011). PRINCIPAL CONCLUSION: Platelet-leukocyte gel, applied locally, can improve knee stability in surgery for reconstruction of the anterior cruciate ligament.

Exploratory thoracotomy and its influence on the survival of patients with lung cancer.

PURPOSE: To evaluate diagnostic procedures, reasons for exploratory thoracotomy (ET), causes of unresectability of lung cancer, possibility for reducing numbers of ETs, and the influence of ET on survival. PATIENTS AND METHODS: Between 1990 and 1999, 1808 patients with lung cancer were operated on. ET was performed in 165 (9.1%) of these cases. In total, 131 ET patients were evaluable for analysis. The clinical stages were: three patients in stage IA, 28 in IB, one in IIA, 35 in IIB, 50 in IIIA, 10 in IIIB (all due to invasion of the mediastinum), and four patients in IV (three with ipsilateral pulmonary and one with solitary suprarenal metastasis). The control group for calculating survival difference consisted of 130 consecutive non-operated patients with comparable characteristics (age, sex, clinical stage, performance status, histology and comorbidity) who were diagnosed during the period 1996-1998. RESULTS: The diagnostic procedure before ET comprised bronchoscopy in all patients, transthoracic needle biopsy in 13, cervical mediastinoscopy in nine, parasternal mediastinotomy in two and thoracoscopy in two, in all patients without proving unresectability. A CT scan was performed in 118 patients indicating resectability in 33%, doubtful resectability in 64% and unresectability in 3%. Clinical and surgical staging were equal in 3% of stage IIB patients, in 24% of stage IIIA, 100% of stage IIIB and 75% of patients in stage IV. The 30-day operative mortality was 4.6%. The reasons for ET were: diagnosis of preoperatively unverified tumor in one patient, necessity for pneumonectomy in the case of poor pulmonary function in 11 patients, and unresectability in 119 (due to invasion of the mediastinum in 98 patients, thoracic wall in three and vertebral body in one, and due to pleural metastases in 17 patients). ET could have been avoided in 15 (11%) patients. The median survival for both ET and control group patients was 11.1 months. The survival difference was not statistically significant (p = 0.420). CONCLUSION: ET could be partly avoided through a more accurate preoperative staging procedure. It does not appear possible to avoid ET in patients with limited pulmonary reserve precluding a resection larger than that predicted, nor to avoid ET as a consequence of intraoperative complications. Despite operative mortality, ET did not significantly influence the survival rate in the present study.

The significance of thoracoscopic mechanical pleurodesis for the treatment of malignant pleural effusions.

BACKGROUND: Malignant pleural effusion (MPE) is a frequent and serious complication of numerous malignant tumors in the human organism. The patients are suffering from the primary disease, and the pleural effusion causes dyspnea, thus reducing the quality of their survival time. In our study we wished to establish the significance of thoracoscopic mechanical pleurodesis (TMP) as a new method for the resolution of this pathology, by comparing the results with those of thoracotomy with pleurectomy (TP) and thoracic drainage (TD). The main criterion for the effectiveness of each method was the absence of pleural effusion in a certain time interval. PATIENTS AND METHODS: 84 patients with recurrent MPE and primary tumors at various locations were divided into three groups according to the type of palliative intervention. The patients were classified according to the indication guidelines for individual procedures and their general condition. Group 1 consisted of 44 patients in whom TMP was performed, group 2 consisted of 17 patients with primary tumors in the thoracic region in whom thoracotomy with pleurectomy (TP) was performed, and in group 3 there were 26 patients with TD. We compared the effectiveness of individual palliative methods by periodical X-ray checks, numbers of complications, length of TD and hospitalization, and changes in spirometric values after individual procedures. The t-test was used in statistic processing of the data. RESULTS: After six months, radiological investigation revealed recurrence of pleural effusion in three patients in group 1 (93.2% efficacy), no recurrence in group 2 (100% efficacy), and recurrence in 18 patients in group 3 (25.0% efficacy). There were fewer postoperative complications in group 1, the duration of TD and hospitalization was significantly shorter, and spirometric values increased. CONCLUSION: TMP is an effective palliative method for the treatment of recurrent pleural effusions, with a minimum number of complications and a short period of hospitalization. After TMP there is significant improvement in respiratory functions, and for the patient it represents a relatively simple surgical procedure. TP is indicated in the treatment of tumors and subsequent MPE in the thoracic region, and TD is indicated in patients who are not suitable candidates for one of the palliative pleurodesis procedures, because of either their poor general condition or a trapped lung.