Oxytocin receptor is a promising therapeutic target of malignant mesothelioma.

Malignant mesothelioma (MM) is one of the most aggressive tumors. We conducted bioinformatics analysis using Cancer Cell Line Encyclopedia (CCLE) datasets to identify new molecular markers in MM. Overexpression of oxytocin receptor (OXTR), which is a G-protein-coupled receptor for the hormone and neurotransmitter oxytocin, mRNA was distinctively identified in MM cell lines. Therefore, we assessed the role of OXTR and its clinical relevance in MM. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and OXTR mRNA expression using The Cancer Genome Atlas (TCGA) datasets. The function of OXTR and the efficacy of its antagonists were investigated in vitro and in vivo using MM cell lines. Consistent with the findings from CCLE datasets analysis, OXTR mRNA expression was highly increased in MM tissues compared with other cancer types in the TCGA datasets, and MM cases with high OXTR expression showed poor overall survival. Moreover, OXTR knockdown dramatically decreased MM cell proliferation in cells with high OXTR expression via tumor cell cycle disturbance, whereas oxytocin treatment significantly increased MM cell growth. OXTR antagonists, which have high selectivity for OXTR, inhibited the growth of MM cell lines with high OXTR expression, and oral administration of the OXTR antagonist, cligosiban, significantly suppressed MM tumor progression in a xenograft model. Our findings suggest that OXTR plays a crucial role in MM cell proliferation and is a promising therapeutic target that may broaden potential therapeutic options and could be a prognostic biomarker of MM.

Airway stenting in patients requiring intubation due to malignant airway stenosis: a 10-year experience.

BACKGROUND: Critically ill patients with severe acute respiratory failure due to malignant airway stenosis often require emergency intubation and mechanical ventilation. Urgent intervention is necessary for the survival of such patients. The aim of this study was to determine the efficacy and outcomes of airway stenting in patients with malignant airway stenosis requiring emergency intubation. METHODS: Patients with malignant airway stenosis who underwent emergency intubation prior to airway stent placement from September 2005 to September 2015 in a single center were retrospectively reviewed. All stenting procedures were performed using both rigid and flexible bronchoscopes under general anesthesia. RESULTS: Thirty patients with malignant airway stenosis (17 with lung cancer, 6 with esophageal cancer, and 7 with other types of malignancy) who required emergency intubation prior to stenting procedures (silicone stenting in 23 and metallic stenting in 7) were analyzed. Extubation within 48 hours after stenting could be performed in 28 of 30 patients (93%). Of the 21 chemoradiotherapy-naïve patients, 18 (86%) received chemotherapy and/or radiation therapy after stenting. No significant complications occurred during the stenting procedures. The median survival after stenting was 198 days (range, 13-3,009 days). CONCLUSIONS: Airway stenting facilitates extubation in critically ill patients with malignant central airway stenosis. It plays an important role as a bridge to additional tumor-specific therapies, especially in chemoradiotherapy-naïve patients.

Rigid bronchoscopic intervention for endobronchial metastasis of renal cell carcinoma.

BACKGROUND: Renal cell carcinoma is one of the major endobronchial metastases, and it occasionally causes life-threatening airway obstruction. Rigid bronchoscopy is useful as a palliative intervention; however, its utility for metastatic renal cell carcinoma has not been elucidated. The purpose of this study was to evaluate the safety and efficacy of rigid bronchoscopic treatment for endobronchial metastasis of renal cell carcinoma. METHODS: Among 550 patients who underwent rigid bronchoscopic intervention at a single center from January 2005 to June 2015, 9 with metastatic renal cell carcinoma were retrospectively reviewed. Procedures were performed with rigid and flexible bronchoscopes under general anesthesia. RESULTS: In total, 20 procedures were performed on 9 patients who underwent stent implantation. Bleeding was observed in 12 (60%) procedures while severe hypoxia was observed in 2 (10%). The required amount of supplemental oxygen successfully decreased after all the 10 procedures (100%) in patients who previously needed it. Median survival after the first procedure was of 260 days (range, 63-913 days). CONCLUSIONS: Rigid bronchoscopic intervention for endobronchial metastasis of renal cell carcinoma is feasible with safety and effectiveness for palliation of airway obstruction, if one prepares sufficiently for massive intraoperative bleeding.

Endobronchial ultrasound-guided transbronchial needle aspiration is useful as an initial procedure for the diagnosis of lymphoma.

BACKGROUND: The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for evaluating hilar, mediastinal and central parenchymal lesions has been well established. However, its utility for diagnosing lymphoma is controversial. The aim of this study was to evaluate the diagnostic utility of EBUS-TBNA for the definitive diagnosis of de novo lymphoma with subtype classification. METHODS: Patients with lymphoma who underwent EBUS-TBNA for diagnostic purposes at a single institution between March 2004 and May 2013 were retrospectively reviewed. RESULTS: Of the 971 patients who underwent EBUS-TBNA during the study period, 19 patients, who did not have a previous history of lymphoma, had a final diagnosis of lymphoma. EBUS-TBNA provided a diagnosis accompanied with subtype classification in 6 patients (32%), a suspicious but not definitive classification in 10 patients (53%), and a negative classification in 3 patients (16%). Immunohistochemical staining for definitive diagnosis was performed in 15 of 16 patients (94%), with suspicious results from routine hematoxylin and eosin staining. No procedure-related complications occurred. CONCLUSIONS: EBUS-TBNA is a useful initial diagnostic procedure, aiding decisions for the management of patients with suspected lymphoma, even though the sensitivity of EBUS-TBNA for diagnosing lymphoma with subtype classification was lower than previously reported.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of small cell lung cancer.

BACKGROUND: Massive lymphadenopathy and direct mediastinal invasion are well-recognized phenomena in patients with small cell lung cancer (SCLC). The aim of this study was to assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of SCLC. METHODS: We retrospectively reviewed the records of 780 patients who underwent EBUS-TBNA at our institution from March 2004 to June 2012. Of these, 101 had a final diagnosis of SCLC. Excluding 3 patients with known SCLC who underwent EBUS-TBNA for staging purposes and including 2 patients who underwent EBUS-TBNA twice for the diagnosis of recurrence after achieving complete response by chemoradiation therapy during the study period, a total of 100 EBUS-TBNA procedures in 98 patients were analyzed. RESULTS: Other diagnostic tests prior to the initial EBUS-TBNA had failed to yield a diagnosis in 41 patients. The overall diagnostic yield of EBUS-TBNA for SCLC was 97% (97 of 100). Rapid on-site cytologic evaluation (ROSE) was performed at the operator's discretion in 77 procedures. ROSE did not have any impact on diagnostic yield (99% with ROSE vs. 90% without ROSE, p=0.1), but the use of ROSE was associated with fewer lesions (mean 1.1 with ROSE vs. 1.6 without ROSE, p<0.01) or aspirates (mean 2.3 with ROSE vs. 4.0 without ROSE, p<0.01). CONCLUSIONS: EBUS-TBNA provided a high diagnostic yield in SCLC with or without ROSE. EBUS-TBNA can be recommended for patients suspected to have SCLC, even if other diagnostic tests have failed.