Dr. Said Chaaban
Said Chaaban, MD; and Zachary Morris, MD, FCCP
Steering Committee Members
Pulmonary Vascular Disease: Estrogen in PAH: Is it good or bad?
The role of sex hormones in the development and perpetuation of pulmonary arterial hypertension (PAH) continues to be an open field of active research. Epidemiology reveals that PAH is more prevalent in women in both idiopathic and heritable cases.1 On the other hand, data demonstrate that prognosis of PAH in men is worse than in women and, in animal research, estrogens provide a protective effect. This constitutes the “estrogen paradox.” Estrogen plays a protective role in the vasculature, modulating proliferative and vasoactive signaling by direct and receptor-mediated mechanisms.2,3 In animal models of PAH, estrogen increases nitric oxide and prostacyclin production and decreases endothelin-1, resulting in beneficial vascular effects.4 However, the Women’s Health Initiative revealed that hormone replacement therapy increases the risk for adverse cardiovascular events.5 In familial PAH, estrogen is a potent mitogen of pulmonary vascular smooth muscle cells.6 A recently published study, first in humans, by Ventetuolo et al.7 showed higher levels of estrogen (E2) and lower level of dehydroepiandrosterone-sulfate (DHEAS) in men with PAH, compared with normal men without cardiovascular disease (MESA study), supporting the role of the estrogen pathway in the development of PAH. Experimental data implicate estrogens as promoters of vascular proliferation and cell damage but also as inhibitors of pulmonary vasoreactivity. In vitro, estrogen is mitogenic and promotes proliferation of pulmonary vascular smooth muscle cells.6 Despite advances, the role of sex and estrogen in PAH is not fully understood. More preclinical and clinical data are necessary to establish a potential role for estrogen-based therapies in this disease.
Dr. Hector Cajigas
Sandeep Sahay, MD; and Hector R Cajigas, MD
Steering Committee Members
References
1. Frost AE, et al. Chest. 2011;139:128.
2. Brouchet L, et al. Circulation. 2001;103:423.
3. Pendaries C, et al. Proc Natl Acad Sci USA. 2002;99:2205.
4. Lahm T, et al. Shock. 2008;30:660.
5. Manson JE, et al. N Engl J Med. 2003;349:523.
6. Farhat MY, et al. Br J Pharmacol. 1992;107:679.
7. Ventetuolo CE, et al. Am J Respir Crit Care Med. 2016;193:1168.
Thoracic Oncology: The “new” lung cancer staging system
Definition of lung cancer stage is an essential part of defining prognosis, developing treatment plans, and conducting and reporting on clinical research studies. The stage classification system is determined by the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC). The 7th edition of the lung cancer staging system, published in 2009, was a landmark effort based on a large multicenter international database created by the Staging and Prognostic Factors (SPFC) of the International Association for the Study of Lung Cancer (IASLC) and backed by careful validation and statistical analysis.
The IASLC Lung Cancer Staging Committee has been working on the 8th edition of the TNM classification for lung cancer. The database used for analysis consists of 94,708 patients diagnosed between 1999 and 2010, and included cases from 35 sources and 16 countries. Multiple analyses were performed to assess the ability of T, N, and M descriptors to predict prognosis and to identify new cutpoints for inclusion in the eight edition.1-3 The proposed changes include new cutpoints for the T component based on 1-cm increments, new categories for the N component, a new M category to specifically identify patients with oligometastatic disease, and multiple updates to the overall TNM stage groupings.4 In addition, the proposal includes recommendations for coding T stage for subsolid nodules and assessment of tumor size in part-solid nodules.5 These proposed changes will be submitted to the UICC and AJCC for inclusion in the eighth edition and will be enacted in January 2017.
Dr. Anil Vachani
Anil Vachani, MD, FCCP
NetWork Vice-Chair
References
1. Rami-Porta R, et al. J Thorac Oncol. 2015;10:990.
2. Eberhardt WEE, et al. J Thorac Oncol. 2015;10:1515.
3. Asamura H, et al. J Thorac Oncol. 2015;10:1675.
4. Goldstraw P, et al. J Thorac Oncol. 2016;11:39.
5. Travis WD, et al. J Thorac Oncol. 2016;11:1204.