The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium. [Cancer Res 2007;67(9):4364-72]
IntroductionVideo-assisted thoracoscopic surgery (VATS) became an option for the treatment of thymomas in the 1990s. Compared to transsternal thymectomy, VATS thymectomy offers shorter hospital stays, reduced postoperative complications and at least equivalent oncologic outcomes (1,2).The benefits of VATS thymectomy have not been specifically studied in elderly patients. One series of 25 septuagenarians and five octogenarians who underwent VATS lobectomies and pneumonectomies showed that over 90% of patients were fit for discharge the next day, with one patient being discharged on the same day (3). We have growing experience with outpatient mediastinal surgery and continue to offer outpatient stays to those who meet criteria.In this case report, we describe an outpatient VATS thymectomy in an 80-year-old male with an enlarging thymoma. To our knowledge, this is the first report of an outpatient VATS thymectomy in an octogenarian. Case presentationThe patient is an 80-year-old male who originally presented to the emergency department with right sided pleuritic chest pain. Chest CT showed a 2.3 cm anterior mediastinal mass. The mass was enlarged to 2.5 cm on a 6-month follow up CT scan ( Figure 1) and he was referred to thoracic surgery. The patient requested the shortest possible hospital stay. Given the size and location of the mass as well as the patient's overall health status, we felt that a same day VATS procedure would be possible.A right sided VATS approach was used with CO 2 insufflation, a single lumen endotracheal tube and three 5 mm ports. The lesion and entire thymus including superior horns were resected and extracted through an enlarged port site. Intercostal blocks were placed. At the completion of the procedure, the lungs were re-expanded under standard protocol and no chest tube was placed. The patient underwent a postoperative chest X-ray (Figure 2) in the post-anesthesia care unit and was discharged home in stable condition five hours after surgery. He returned to clinic two weeks later for standard follow-up and was doing well.Pathology revealed a World Health Organization (WHO) B1 lymphocyte rich thymoma. The patient is well without recurrence three years following his surgery. Abstract: Video-assisted thoracoscopic thymectomy has gained acceptance for the treatment of small thymomas. Appropriately selected elderly patients may benefit as much as younger patients from this procedure.Specific benefits of minimally invasive surgery include shorter hospital stays, decreased complications and improved oncologic outcomes. Outpatient thoracic surgery is an established model for some procedures. In this report, we present an 80-year-old patient with an enlarging 2.5 cm thymoma who successfully underwent an outpatient right video-assisted thoracoscopic thymectomy at our institution. The patient's postoperative course was uncomplicated. He continues to do well 3 years after his surgery. To our knowledge, this is the first reported outpatient video-assisted thoracoscopic thymectomy in an octogenarian.
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