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Unsuspected pulmonary embolism: impact on mortality among cancer patients

imagePurpose of review: Symptomatic pulmonary embolism is associated with significant morbidity and mortality, but whether the same is true of unsuspected pulmonary embolism (UPE) has only recently become the subject of clinical research. Interest in the impact of UPE on patient outcomes has emerged, as their detection has become more common with the standard use of multirow detector computed tomography scans. Serial CT scanning of patients with cancer, in conjunction with a higher incidence of venous thromboembolism, makes UPE the most frequent in this population. This review will explore the recent studies which evaluate the impact of UPE on outcomes, especially mortality, among patients with cancer.

Recent findings: Several recent studies have attempted to explore the impact that UPE has on cancer patients, mainly with respect to mortality. These studies have all been retrospective and most have used as a comparator cancer patients with suspected pulmonary embolism based on suggestive symptoms. Regardless, the findings in all but one study conclude that UPE adversely impacts survival among cancer patients, even with proper anticoagulation. However, unsuspected subsegmental pulmonary embolism may not impact survival, regardless of the treatment.

Summary: Recent data suggest that cancer patients who develop UPE have mortality rates as well as bleeding rates that parallel those of cancer patients in whom pulmonary embolism is detected on dedicated scans performed because of the presence of pulmonary embolism-related symptoms. Cancer patients who are truly asymptomatic, based on careful screening, may have improved survival, although no prospective studies support definitive treatment recommendations for this group.

Into the matrix: targeting fibroblasts in pulmonary fibrosis

imagePurpose of review: This review describes the challenges created by the existence of multiple molecular pathways leading to fibrosis and proposes that attention be focused on targeting the fibroblasts and myofibroblasts which themselves produce multiple cytokines and growth factors as well as the extracellular matrix, which is the hallmark of fibrotic lung disease.

Recent findings: The last 20 years have seen remarkable progress in our understanding of the molecular pathogenesis of pulmonary fibrosis leading to multiple programmes in drug discovery, and there are currently 15 actively recruiting trials registered on http://www.clinicaltrials.gov . Unfortunately, at this time only one new drug, pirfenidone, has progressed to approval for use in patients. Part of the frustration is that drugs that are effective in targeting inflammatory pathways have been ineffective in lung fibrosis. This may result from the inability to treat patients early in the disease process but it is also likely that pathways independent of inflammation can drive fibrosis.

Summary: We further propose that this approach should inhibit fibrosis independent of cell type or the signalling cascade that is activating these cells. We are hopeful that the next 20 years will see many more therapeutic options for patients suffering with fibrotic lung disease.

Outcome of incidentally diagnosed pulmonary embolism in patients with malignancy

imagePurpose of review: With improvements in the quality of computed tomography (CT) examinations, pulmonary embolism is increasingly being detected incidentally in oncology patients undergoing routine cancer staging CT scans. The purpose of this review is to update current evidence on the prognosis of cancer patients diagnosed with incidental pulmonary embolism.

Recent findings: Several recent observational studies have shed some light on the prognostic implications of diagnosing incidental pulmonary embolism in cancer patients. In general, anticoagulant treatment is initiated in these patients. Even during treatment, recurrent venous thromboembolic events may occur with a frequency that is comparable to cancer patients who have symptomatic pulmonary embolism. It has been demonstrated that the diagnosis of incidental pulmonary embolism is associated with adverse survival in cancer patients, and the long-term mortality rate in incidental pulmonary embolism patients seems to approach that of symptomatic pulmonary embolism patients.

Summary: Overall, the body of literature on patients with incidental pulmonary embolism is sparse and does not allow firm recommendations on the therapeutic approach to these patients. Yet, in the absence of data on the natural clinical course of these patients, and the presence of cohort studies suggesting that incidental pulmonary embolism may impact recurrent venous thromboembolism and mortality, current consensus is to treat these patients in the same manner as symptomatic patients.

Sarcoidosis and tuberculosis: the same disease with different manifestations or similar manifestations of different disorders

imagePurpose of review: Ever since sarcoidosis was first described, its relationship with tuberculosis has been debated. Whereas some consider sarcoidosis and tuberculosis as two extremes of the same disease process, other researchers have negated the role of mycobacteria in causation of sarcoidosis. Whether or not linked causally, there are obvious clinical similarities that make differential diagnosis of the two conditions very challenging, particularly in countries with high burden of tuberculosis. Herein we analyze the relationship between sarcoidosis and tuberculosis and its implications in clinical practice.

Recent findings: Initial studies had focused on finding an epidemiological link between the two conditions or demonstration of mycobacteria in sarcoid lesions on histology. Results from these studies were at best suggestive. Recent molecular and immunological studies suggest mycobacterial antigens are the inciting agents in a proportion of sarcoidosis patients. Evidence is stronger from countries with high burden of tuberculosis. Tuberculosis can manifest as a complication of treatment in sarcoidosis and the two conditions can rarely co-exist.

Summary: The balance of evidence favors mycobacteria or their products as a trigger for inciting immune responses leading to sarcoidosis in a proportion of patients, which is likely to be higher in countries with high tuberculosis burden. This evidence also highlights the limitations of molecular or serological studies to discriminate between the two conditions.

Comparative manifestations and diagnostic accuracy of high-resolution computed tomography in usual interstitial pneumonia and nonspecific interstitial pneumonia

imagePurpose of review: Of the idiopathic interstitial pneumonias, the differentiation between idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonitis (NSIP) raises considerable diagnostic challenges, as their clinical presentations share many overlapping features. IPF is a fibrosing pneumonia of unknown cause, showing a histologic pattern of usual interstitial pneumonia (UIP), and has a poorer prognosis than does NSIP.

This review examines whether the radiographic features of IFP and NSIP as assessed by high-resolution computed tomography (HRCT) can be used to distinguish between these two entities.

Recent findings: The diagnostic accuracy of HRCT for UIP and NSIP has been reported to be approximately 70% in various studies. Disagreement between the HRCT diagnosis and the histologic diagnosis occurs in approximately one-third of the cases. The predominant feature of honeycombing on HRCT yields a specificity of approximately 95% and sensitivity of approximately 40% for UIP. In contrast, a predominant feature of ground glass opacities (GGOs) gives a sensitivity of approximately 95% and specificity of approximately 40% for NSIP.

Summary: The finding of honeycombing as the predominant HRCT feature suggests the diagnosis of UIP and may exclude the need for biopsy. Predominant features of GGOs are not specific enough to distinguish between NSIP and UIP.

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