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Intrapleural 'outside-in' gene therapy: therapeutics for organs of the chest via gene transfer to the pleura.

The pleural space is an attractive site for using viral vectors to deliver gene products to the lung parenchyma, other thoracic structures and the systemic circulation. The advantages of intrapleural gene transfer using viral vectors include: (i) easy accessibility; (ii) large surface area; (iii) ability to provide high concentrations of secreted gene products to chest structures; (iv) low risk of detrimental effects of possible vector-induced inflammation compared with intravascular delivery; and (v) because it is local, lower vector doses can be used to deliver therapeutic genes to thoracic structures than less efficient systemic routes. Examples of pleural gene transfer include the use of adenovirus vectors to treat mesothelioma by transiently expressing genes that encode toxic proteins, immunomodulatory molecules or anti-angiogenesis factors. Intrapleural delivery of adeno-associated viral vectors represents an efficient strategy to treat alpha1-antitrypsin (alpha1AT) deficiency, achieving high lung and systemic therapeutic levels of alpha1AT. Intrapleural delivery of gene transfer vectors holds promise for the treatment of diseases requiring transient, localized gene expression, as well as sustained expression of genes to correct hereditary disorders requiring localized or systemic expression of the therapeutic protein.

Adenoviridae↗

[Pseudomyxoma of the pleura and peritoneum].

A case is presented of 41 year old patient with a very rare form of clinical manifestation of adenocarcinoma with a large mucinous ascites with abdominal distention and a massive left hemithoracic content with same characteristics. Two years prior the patient suffered from acute abdomen and underwent apendectomy with slow wound healing and a stomach edema 6 months later with a finding of smaller changes on the left side of the thorax. The patient was hospitalized when he already had an advanced stage of the disease. The diagnosis of adenocarcinoma was reached with percutaneous thoracic biopsy and finding of mucinous malignant cells. Gelatinoid ascites was confirmed on CT an echography with the same finding in the thorax. Systemic chemotherapy was initiated without major effect followed by intrapleural and intraabdominal instillation of hyaluronidase in combination with cytostatics. The course of the disease and treatment effects were followed echographically and on CT. According to available literature this is the first case report of a patient with mucinous adenocarcinoma and a presentation of pseudomyxoma of the thoracic and abdominal cavities.

Adenocarcinoma, Mucinous↗

Malignant mesothelioma of the pleura among seafarers.

BACKGROUND: A large amount of data indicates that seafarers are at risk for asbestos disease. OBJECTIVES: To trace the outlines of pleural mesothelioma among seafarers. METHODS: Pleural mesotheliomas diagnosed among seamen in the Trieste-Monfalcone area, Italy, in the period 1973-2003, were reviewed. RESULTS: The series comprised 50 men aged between 53 and 91 years (mean age 75.7 years). The diagnosis of mesothelioma was confirmed by necropsy in 38 cases. The patients had served in the Italian Navy (24 persons), in the merchant navy (17 persons), or in both (9 persons). The trades were various including engine room as well as deck personnel. Asbestos bodies were detected on routine lung sections in 55% of the necropsy cases. Asbestos bodies isolated from the lungs in three cases ranged between 2100 and 7000 bodies per gram of dried tissue. Latency periods ranged between 33 and 72 years (mean 56.1 years). CONCLUSIONS: When compared with shipyard workers, the seamen with mesothelioma show signs of less intense exposure to asbestos, and longer latency periods. Mesothelioma in seamen should be considered as an occupational disease.

Age Factors↗

[Metastasis in lung and pleura].

The Topography, extent and histopathology of lung and pleural metastases in 132 surgical resections were investigated with regard to primary tumours. The emphasis was on postmortaly obtained angiographic results of the neovascularisation of metastases, mainly by vessels of the functional pulmonary circulation with diameters of 20-60 microns. Different phases of metastatic spread were considered such as invasion, embolisation and implantation. The pathologic-anatomic investigation of metastases is becoming more and more important for morphological quantification of tumour regression following cytostatic therapy and for clarifying unknown primary tumours by the immunohistochemical examination of lung metastases.

Humans↗