Bitter tastants can activate bitter taste receptors on constricted smooth muscle cells to inhibit L-type calcium channels and induce bronchodilation.

The etiology of airway hyperresponsiveness associated with asthma requires an understanding of the regulatory mechanisms mediating human airway smooth muscle cell (SMC) contraction. The objective of this study was to determine how human airway SMC contraction (induced by histamine) and relaxation (induced by formoterol) are regulated by Ca 21 oscillations and Ca 21 sensitivity. The responses of human small airways and their associated SMCs were studied in human lung slices cut from agarose-inflated lungs. Airway contraction was measured with phase-contrast video microscopy. Ca 21 signaling and Ca 21 sensitivity of airway SMCs were measured with two-photon fluorescence microscopy and Ca 21 -permeabilized lung slices. The agonist histamine induced contraction of human small airways by stimulating both an increase in intracellular Ca 21 concentration in the SMCs in the form of oscillatory Ca 21 waves and an increase in Ca 21 sensitivity. The frequency of the Ca 21 oscillations increased with histamine concentration, and correlated with increased contraction. Formoterol induced airway relaxation at low concentrations by initially decreasing SMC Ca 21 sensitivity. At higher concentrations, formoterol additionally slowed or inhibited the Ca 21 oscillations of the SMCs to relax the airways. The action of formoterol was only slowly reversed. Human lung slices provide a powerful experimental assay for the investigation of small airway physiology and pharmacology. Histamine induces contraction by simultaneously increasing SMC Ca 21 signaling and Ca 21 sensitivity. Formoterol induces long-lasting relaxation by initially reducing the Ca 21 sensitivity and, subsequently, the frequency of the Ca 21 oscillations of the airway SMCs.Keywords: lung slice; smooth muscle cell; two-photon microscopy; hyperresponsiveness; histamine Because increased airway smooth muscle cell (SMC) contraction is a major characteristic of airway hyperresponsiveness (AHR) associated with asthma (1), a prerequisite to address AHR is an understanding of the mechanisms that regulate airway SMC contraction. It is well established that airway SMC contraction is regulated by the phosphorylation of the regulatory myosin light chain (rMLC) (2, 3) to induce its interaction with adjacent actin filaments via the classical mechanism of cross-bridge cycling to generate force (4). (5)(6)(7)(8). Although the frequency of these Ca 21 oscillations has been found to increase with agonist concentration, and that this correlates with increased contraction, the frequency of the Ca 21 oscillations generated by similar agonist concentrations differs considerably between species (9).To induce SMC relaxation, the increase in [Ca 21 ] i is generally reversed to inactivate MLCK, but the cessation of the cross-bridge cycle requires that the rMLC is dephosphorylated; this reaction is mediated by MLC phosphatase (MLCP). With the exception of mice (10), the activity of MLCP appears to be Ca 21 independent, but is regulated by the same agonists that stimulate increases in [Ca 21 ] ...

BackgroundLittle is understood regarding the inter-relation between economic, marital, and racial/ethnic differences in presentation and survival of surgically resected lung cancer patients. Our investigation will assess these differences in addition to known therapeutic, patient, and histopathologic factors.MethodsA retrospective review of the Surveillance Epidemiology and End Reporting database was conducted through the years 2007–2012. The population was split into nine different ethnic groups. Population differences were assessed via chi-square testing. Multivariable analysis (MVA) were used to detect overall survival (OS) differences in the total surgical population (TS, N = 35,689) in an ear (T1–T2 < 4 cm N0) surgical population [early-stage resectable (ESR), N = 17,931]. Lung cancer-specific survival (LCSS) was assessed in the ESR.ResultsIn the TS population, as compared to Whites, Blacks, and Hispanics presented with younger age, more adenocarcinomas, lower rates of marriage, lower rates of insurance, less stage I tumors, and had less nodes examined, but their type of surgical procedures and OS/LCSS were the same. MVA demonstrated that lower OS and LCSS were associated with males, single/divorced/widowed partnership, lower income (TS only), and Medicaid insurance. MVA also found that Blacks and Hispanics had a similar OS/LCSS to Whites and that all ethnic groups were associated with a similar or better outcomes. The 90-day mortality and positive nodes were correlated with not having insurance and not being married, but they were not associated with ethnicity.ConclusionIn TS and ESR groups, OS was not different in the two largest ethnic groups (Black and Hispanic) as compared to Whites, but was related to single/widowed/divorced status, Medicaid insurance, and income (TS group only). Nodal positivity was associated with patients who did not have a married partner or insurance suggesting that these factors may impact disease biology. Economic and psychosocial variables may play a role in survival of ear lung cancer in addition to standard histopathologic and treatment variables.

First described in 2005, the Mullerian derived cyst in the mediastinum is a rare finding with few subsequent reports. We report a case of Mullerian cyst occurring in the mediastinum of a 49-year-old female that was resected by robot-assisted thoracoscopic surgery. To our knowledge, this is the first report of robot-assisted resection of Hattori's cyst. Histopathologic analysis revealed ciliated Mullerian-type tubal epithelium positive for paired box gene 8 (PAX8), estrogen receptor (ER), and progesterone receptor (PR), confirming Mullerian differentiation. We also review the clinical presentation, pathology, and differential diagnosis of such cysts.

Background and Aims: Frail older adults are more than twice as likely to experience postoperative complications. Preoperative exercise may better prepare these patients through improved stamina and mobility experienced in the days following surgery. We measured the impact of a walking intervention using an activity tracker and coaching on postoperative stamina, and mobility in older adults with frailty traits. Methods:We included patients aged 60+ and scoring 4+ on the Edmonton Frailty Scale. We then randomized patients to intervention versus control stratified by anticipated hospital stay (1 night vs. 2+ night) and baseline stamina (i.e., 6-min walk distance [6MWD]). Intervention patients received an activity tracker and linked smart phone. An athletic trainer (AT) prescribed a daily step count goal and titrated this up after checking in with patients during weekly telephone calls. Controls received general walking recommendations. We then measured postoperative 6MWD 1-3 days after surgery. We also assessed postoperative mobility by measuring steps walked the day after surgery using a thigh-worn monitor. Because many patients could not walk postoperatively, we compared intervention-control difference in both 6MWD and steps using Wilcoxon rank testing and Tobit and ordinal logistic regression adjusting for several patient characteristics.Results: We randomized 104 eligible patients; 80 patients remained for final analysis. There was no difference in intervention versus control postoperative 6MWD (median 72 vs. 74 m Wilcoxon p = 0.54) or postoperative steps taken

Purpose: Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall.Materials and Methods: Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis.Results: In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20).Conclusions: VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.

Purpose: To identify the incidence, preoperative risk factors, and prognosis associated with pathologically positive lymph node (pN+) in patients undergoing a sub-lobar resection (SLR). Methods: This is a retrospective study using the National Cancer Database (NCDB) from 2004 to 2014 analyzing SLR excluding those with any preoperative chemotherapy and/or radiation, follow-up <3 months, stage IV disease, or >1 tumor nodule. Multivariable modeling (MVA) was used to determine factors associated with overall survival (OS). Propensity score matching (PSM) was used to determine preoperative risk factors for pN+ in patients having at least one node examined to assess radiation's effect on OS in those patients with pN+ and to determine whether SLR was associated with inferior OS as compared to lobectomy for each nodal stage. Results: A total of 40,202 patients underwent SLR, but only 58.3% had one lymph node examined. Then, 2,615 individuals had pN+ which decreased progressively from 15.1% in 2004 to 8.9% in 2014 (N1, from 6.3 to 3.0%, and N2, from 8.4 to 5.9%). A lower risk of pN+ was noted for squamous cell carcinomas, bronchioloalveolar adenocarcinoma (BAC), adenocarcinomas, and right upper lobe locations. In the pN+ group, OS was worse without chemotherapy or radiation. Radiation was associated with a strong trend for OS in the entire pN+ group (p = 0.0647) which was largely due to the effects on those having N2 disease (p = 0.009) or R1 resections (p = 0.03), but not N1 involvement (p = 0.87). PSM noted that SLR was associated with an inferior OS as compared to lobectomy by nodal stage in the overall patient population and even for those with tumors <2 cm. Varlotto et al. Incidence and Outcomes of SLRs With Positive Nodes Conclusion: pN+ incidence in SLRs has decreased over time. SLR was associated with inferior OS as compared to lobectomy by nodal stage. Radiation appears to improve the OS in patients undergoing SLR with pN+, especially in those with N2 nodal involvement and/or positive margins.

Pulmonary papillary adenomas are rare neoplasms that predominantly occur in the periphery of the lung. We describe a 24-year-old male with a 6.0-cm spherical mass found incidentally at the periphery of the left upper lobe by imaging. Enucleation of the neoplasm was performed with intraoperative frozen section analysis. The tumor histologically showed papillary proliferations containing fibrovascular cores lined by a single layer of tumor cells that lacked atypia, mitoses, or necrosis. The histologic features were consistent with a pulmonary papillary adenoma. Pulmonary papillary adenoma was previously considered to be a benign entity. However, because of its invasive growth pattern, it has been suggested that this neoplasm has intermediate malignant potential. The clinicopathologic features and differential diagnosis of this unusual neoplasm is discussed with a review of the English literature.