Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2008
ReviewTargeted therapy in advanced non-small-cell lung cancer.
Molecularly targeted therapies have recently expanded the options available for patients with advanced non-small-cell lung cancer (NSCLC). Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathway. The former has emerged as a key regulator of cancer cell proliferation and invasion, and several EGFR inhibitors have been developed. ⋯ Because preclinical data suggest a synergistic effect when VEGF and EGFR inhibitors are combined, the concurrent use of erlotinib and bevacizumab has additionally been evaluated in a phase II trial, with encouraging early results suggesting at least equivalent activity to standard salvage chemotherapy, with less toxicity. Several other novel agents are being examined, including inhibitors of histone deacteylases and the 26S proteosome. Research efforts are currently focusing on tailoring such therapies according to predictive clinical and molecular markers.
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The past decade has seen steady advances in the field of radiation therapy, impacting definitive treatment options for early and advanced tumors, as well as identifying further roles for adjuvant and palliative therapy. The widespread availability of (18)F-fluoro-2-deoxy-D-glucose positron emission tomographic (FDG PET) imaging has improved staging, and better defines a population that will benefit from aggressive local therapy. Technological advances in radiation treatment planning allow for less normal lung irradiation, allowing increasing dose and decreasing normal tissue toxicity. Ongoing clinical investigations in the role of radiosurgery for early lung tumors, postoperative radiation of locally advanced non-small-cell lung cancer (NSCLC), and prophylactic cranial irradiation in small-cell lung cancer (SCLC) help to identify patients who may benefit from treatment.
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Paracoccidioidomycosis (formerly known as South American blastomycosis) is produced by the thermally dimorphic fungus Paracoccidioides brasiliensis. Most often this mycosis runs a chronic progressive course affecting preferentially the lungs followed by the skin, mucous membranes, adrenals, and reticuloendothelial organs. Acute-subacute presentations can be observed in children and immunosuppressed patients. ⋯ No outbreaks have been reported. P. brasiliensis is capable of entering into prolonged periods of latency as is demonstrated by its diagnosis in patients who have moved outside the recognized endemic areas. This review updates clinicians and laboratory workers on the characteristics of a mycosis seldom reported outside of the Latin American countries.
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Pulmonary manifestations of histoplasmosis were last reviewed in Seminars in 2004. This review highlights the management of the most common clinical syndromes, emphasizing recognition, diagnosis, and treatment. The reader is referred to the earlier review for subjects not fully addressed herein. ⋯ Antigen testing is most useful in patients with more diffuse pulmonary involvement and those with progressive disseminated disease due to the high fungal burden. Detection of antigen in bronchoalveolar lavage fluid may be particularly helpful in certain circumstances. Guidelines for antifungal therapy have been updated and will be discussed for pulmonary syndromes.
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The frequency and diversity of serious fungal infections are increasing. Persons who are severely immunocompromised are particularly vulnerable to infection from unusual molds and yeasts that are often found naturally in the environment. Clinical manifestations from these unusual fungal infections range from colonization of airways to chronic localized lesions to acute invasive or disseminated disease. ⋯ Furthermore, many emerging opportunistic molds demonstrate in vitro resistance to the older azoles and amphotericin B. As a result, successful treatment may require adjunct surgical debridement and, when possible, reconstitution of the host immune system. Also, the newer triazoles such as voriconazole and posaconazole may be useful to treat some of these infections caused by rare and emerging molds.